Rejected

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15μg H7N9, 1B) IB160 + 7.5μg H7N9, 1C) IB160 + 3.75μg H7N9, 2A) SE + 15μg H7N9, 2B) SE + 7.5μg H7N9, 2C) SE + 3.75μg H7N9, 3) unadjuvanted vaccine 15μg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.

Neuropathic pain remains a chronic and intractable pain. Recent studies have shown a close relationship between gamma-aminobutyric acid A (GABAA) receptor and neuropathic pain. Spinal cord GABAA receptors are key modulators of pain processing. Electroacupuncture (EA) is currently used worldwide to relieve pain. The immunomodulatory effect of EA in animals has been proposed in previous studies. However, it remains unclear how EA contributes to alleviating neuropathic pain. In this study, the chronic constriction injury (CCI) rat model was used to explore the relationship between GABAA receptor and neuropathic pain. We also investigated whether EA treatment could ameliorate pain hypersensitivity by modulating the GABAA receptor. To determine the function of EA in neurological diseases, in this study, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed to determine the threshold of pain. In addition, we used Western blot, immunofluorescence, and real-time quantitative PCR to confirm whether EA treatment relieves pain hypersensitivity by regulating GABAA receptors. The morphology of synapse was examined using an electron microscope. In the present study, EA relieved mechanical allodynia and thermal hyperalgesia. EA also inhibited microglial activation in the spinal cord, accompanied by increased levels of GABAAR2, GABAAR3, and GABAAR2 subunits. However, the analgesic effect of EA was attenuated by treatment with the GABAA receptor antagonist bicuculine. Overall, the present results indicate that microglia and GABAA receptor might participate in EA analgesia. These results contribute to our understanding of the impact of EA on rats after sciatic nerve compression, providing a theoretical basis for the clinical application of EA analgesia.

The pain pattern after laparoscopic cholecystectomy (LC) is complex and distinct from postoperative pain after other laparoscopic procedures, suggesting that procedure-specific optimal analgesic management plans should be proposed. Duloxetine, a non-opioid neuromodulator, has been widely used to manage pain with dual central and peripheral analgesic properties. To assess the effect of preoperative administration of duloxetine compared to placebo on postoperative pain control in patients undergoing LC. This study was a randomized, parallel-group, placebo-controlled, double-blinded study performed on patients undergoing LC. Patients were randomly divided into two groups of 30 each on the day of surgery in the preoperative holding area, using a computer-generated random number to receive 60 mg duloxetine as a single oral dose 2 h before the procedure or placebo. The primary outcome was the difference in the mean of visual analogue scale (VAS) scores between the two studied groups, as measured by the area under the curve (AUC) of the VAS scores. The derived AUC of VAS scores in the duloxetine group (757.89 ± 326.01 mm × h) was significantly lower than that calculated for the control group (1005.1 ± 432.5 mm × h). The mean postoperative VAS scores recorded at 4 and 24 h were statistically different between the study groups ( = 0.041 and 0.003, respectively). As observed in the survival curve analysis, there was no significant difference ( = 0.665) for the time until the patient's first request for rescue medications in the two groups. The frequency of postoperative nausea and vomiting (PONV) was lower in patients of the duloxetine group than that recorded in those allocated to the control group at 8 and 24-h time intervals ( = 0.734 and 0.572, respectively). Preoperative use of duloxetine reduces postoperative pain significantly compared with placebo. In addition, its use is associated with a reduction in PONV. These preliminary findings suggest that duloxetine could play a role in the acute preoperative period for patients undergoing LC. [https://clinicaltrials.gov/ct2/show/NCT05115123, identifier NCT05115123].

Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10-6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.

Vertebral augmentation techniques are widely used to treat osteoporotic vertebral compression fractures (OVCFs). Superior analgesic effects and shortened bed rest time means patients recover quickly, but prolonged unscheduled hospitalization can increase medical expenses and the risk of bed rest complications. The aim of this study was to investigate the reasons for prolonged hospitalization after vertebral augmentation surgery and to determine the relative risk factors.

To investigate the clinical efficacy of ultrasound (US) combined with neuromuscular electrical stimulation (NMES) in treating lumbar disc herniation (LDH) and its effect on the level of inflammatory factors.

There is a growing body of mitochondrial disorders that are associated with headaches, albeit only one of them is currently listed in the latest International Classification of Headache Disorders, 3rd edition (ICHD-3). Headache frequency and headache presentation can vary widely in this respective patient group. Acute and preventive migraine treatment can be quite challenging-the use of several established medications is often limited due to their side effects in the setting of mitochondrial dysfunction and multi-organ disease.

The role of daytime variation in the comprehensive pharmaceutical effects of commonly used opioid analgesics in clinical setting remains unclear. This study aimed to explore the differences in daytime variation among elective surgery patients who were scheduled to receive preemptive analgesia with equivalent doses of sufentanil, dezocine, and tramadol in the morning and afternoon. The analgesic effect was assessed by changes in the pressure pain threshold before and after intravenous administration of sufentanil, dezocine, and tramadol. Respiratory effects were evaluated using pulse oximetry, electrical impedance tomography, and arterial blood gas analysis. Other side effects, including nausea, sedation, and dizziness, were also recorded, and blood concentration was measured. The results showed that the analgesic effects of sufentanil, dezocine, and tramadol were significantly better in the morning than in afternoon. In the afternoon, sufentanil had a stronger sedative effect, whereas dezocine had a stronger inhibitory respiratory effect. The incidence of nausea was higher in the morning with tramadol. Additionally, significant differences in different side effects were observed among three opioids. Our results suggest that the clinical use of these three opioids necessitates the formulation of individualized treatment plans, accounting for different administration times, to achieve maximum analgesic effect with minimal side effects.

Osteitis fibrosa cystica is a rare complication of secondary hyperparathyroidism. Even though it is thought to be a disease of the past, it still continues to be seen in this modern era in the setting of undiagnosed or untreated chronic kidney disease.

There is no standard effective treatment for schizophrenia-associated cognitive impairment. Efforts to use non-invasive brain stimulation for this purpose have been focused mostly on the frontal cortex, with little attention being given to the occipital lobe.