To establish and evaluate the Chinese rhesus model of tuberculosis.Twelve Chinese rhesus macaques, randomly divided into 3 groups, were inoculated with 2 different doses of Mycobacterium tuberculosis H(37) Rv strain via both bronchoscopic and intratracheal instillation into the lungs. Clinical observation and laboratory examinations were performed, including erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test and X-ray examination. Histopathological assessments were performed in the 24th week postinfection. Statistical analysis was performed by ANOVA in the 3 groups.After infection all the animals manifested fever, weight lose, lack of appetite, coughing and other symptoms of tuberculosis. The temperature gradually increased and reached a peak [(40.1 ± 0.2)°C] at the 8th week postinfection. The weight decreased significantly at 24th week postinfection (-5.5 ± 5.6)%. Erythrocyte sedimentation rate elevated significantly at the 6th to 8th week postinfection (36 ± 40) mm/1 h. C-reactive protein was significantly increased at the 6th to 24th week after infection (75.8 ± 49.8) mg/L. The positive rate of tuberculin skin test was 100%. In Group I (bronchoscopic instillation, 20 CFU) the disease developed slowly, and the main manifestation of chest X-ray was patchy shadows. In group II (bronchoscopic instillation, 100 CFU) and group III (intratracheal instillation, 100 CFU) the disease developed rapidly, and the main manifestation of chest X-ray was patchy and nodular lesions during the 4th to the 12th week postinfection, but became large patchy and consolidation lesions during the 12th to the 24th week postinfection. Tuberculosis granuloma and caseous necrosis, similar to the pathological changes of human tuberculosis, were found in the lungs, mediastinal lymph nodes, kidney and spleen. The results of acid-fast stain were positive. The most serious pathological manifestations were observed in group II, followed by group III and group I. The highest bacterial load of the right lung was seen in group II, followed by group I and group III.A chinese rhesus model of tuberculosis was successfully developed via both bronchoscopic and intratracheal instillation. Their clinical manifestations, disease progression and pathological changes were similar to human primary tuberculosis and hematogenous disseminated tuberculosis.
Systemic juvenile idiopathic arthritis (sJIA) is an aggressive form of childhood arthritis accompanied by persistent systemic inflammation. Patients with sJIA often exhibit poor response to conventional disease-modifying antirheumatic drugs, and chronic glucocorticoid use is associated with significant adverse effects. Although biologics used to target interleukin 1 and interleukin 6 are efficacious, the long-term commitment to frequent injections or infusions remains a challenge in young children. Janus-activated kinase (JAK) inhibitors block the signaling of numerous proinflammatory cytokines and are now used clinically for the treatment of rheumatoid arthritis in adults. Whether this new class of medication is effective for sJIA has not been reported. Here, we describe the case of a 13-year-old girl with recalcitrant sJIA characterized by polyarticular arthritis, fever, lymphadenopathy, and serological features of inflammation. She showed minimal response to nonsteroidal antiinflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs, and etanercept. She also developed osteoporosis and vertebral compression fracture as the result of chronic glucocorticoid therapy. Oral therapy with the JAK inhibitor tofacitinib was initiated, and the patient experienced steady improvement of both arthritis and systemic features. Complete remission was achieved after 3 months, and no evidence of disease activity or adverse effects was seen through 6 months of follow-up. Our experience reveals the effectiveness of JAK inhibition in a case of refractory sJIA. Tofacitinib is an intriguing oral alternative to the available biologics for children with sJIA, and its efficacy and safety should be further assessed by clinical trial.
To observe the expression of cyclophilin A (CyPA) and the effects of lipopolysaccharide (LPS) on CyPA expression in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and evaluate the potential significance of CyPA in the regulation of the onset and development of inflammation process in RA patients.SF were separated and cultured from synovial tissues of 12 patients with RA, 9 with osteoarthritis (OA) and 5 with knee trauma. The protein and mRNA expression levels of CyPA in SF were detected by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) respectively. Correlation analysis was conducted between the protein expression of CyPA in SFs and clinical parameters. Then the effects of LPS on CyPA in SF from 3 groups were detected.The expression levels of CyPA protein and mRNA in RA group were 0.86 ± 0.47 and 0.54 ± 0.22 respectively, significantly higher than those in OA group (0.40 ± 0.31 and 0.03 ± 0.02, P < 0.05) and trauma group (0.34 ± 0.21 and 0.03 ± 0.01, P < 0.05). The protein expression level of CyPA in SF of RA group had positive correlations with erythroeyte sedimentation rate (ESR), rheumatoid factor (RF) and swelling joint counts (SJC) (P < 0.05). After LPS treatment, CyPA protein and mRNA levels were 2.65 ± 1.16 and 1.82 ± 0.39 in RA SF and they were significantly higher than those in RA SF without LPS treatment (P < 0.05). The CyPA expression of SF from OA and trauma groups slightly decreased after LPS treatment.However the differences were not statistically significant (P > 0.05).The expression of CyPA is up-regulated in SF and it is positively correlated with ESR, RF and SJC in RA patients. It indicates that CyPA may be involved in the regulation of the onset and development of inflammation process of RA. And LPS may promote the expression of CyPA in SF of RA patients.
Abstract Objective : Robotic and laparoscopic surgery for rectal cancer have been applied in clinic for decades, nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis is to compare the postoperative complications between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials. Methods: Randomized controlled trials (until May 2020) which compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMbase, Cochrane library, CNKI, Wan Fang databases and CBM. Data regarding sample size, clinical and demographic characteristics, overall postoperative complications, and the incidence of anastomotic leakage、incision infection、bleeding、 ileus、respiratory complications、 urinary complications、unscheduled reoperation 、perioperative mortality were extracted. The results were analyzed using RevMan v5.3. Results : Seven randomized controlled trials which included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications [Z=1.1，OR=1.18，95% CI (0.88-1.57), P=0.27], anastomotic leakage [Z=0.96, OR=1.27, 95% CI (0.78-2.08), P=0.34], incision infection [Z=0.18, OR=1.05, 95% CI (0.61-1.79), P=0.86], bleeding [Z=0.19, OR=0.89, 95% CI (0.27-2.97), P=0.0.85], ileus [Z=1.47, OR=0.66, 95% CI (0.38-1.15), P=0.14], respiratory complications [Z=0.84, OR=0.64, 95% CI (0.22-1.82), P=0.40], urinary complications [Z=0.66, OR=1.22, 95% CI (0.67-2.22),P=0.51], unscheduled reoperation [Z=0.14, OR=0.91, 95% CI (0.26-3.20), P=0.89], perioperative mortality [Z=0.28, OR=0.79, 95% CI (0.15-4.12), P=0.78] were similar between robotic and laparoscopic rectal surgery. Conclusion : Robotic surgery for rectal cancer was comparable to laparoscopic surgery with respect to postoperative complications.
ABSTRACT Objectives To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated. Methods This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada–Denmark magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions. Results Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The Canada–Denmark scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities. Conclusions Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.
Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to their poor stability, most current mRNA delivery platforms need to be stored at -20°C or -70°C, which severely limits their distribution. Herein, we present lyophilized SARS-CoV-2 mRNA-lipid nanoparticle vaccines, which can be stored at room temperature with long-term thermostability. In the in vivo Delta virus challenge experiment, lyophilized Delta variant mRNA vaccine successfully protected mice from infection and cleared the virus. Lyophilized omicron mRNA vaccine enabled to elicit both potent humoral and cellular immunity. In booster immunization experiments in mice and old monkeys, lyophilized omicron mRNA vaccine could effectively increase the titers of neutralizing antibodies against wild-type coronavirus and omicron variants. In humans, lyophilized omicron mRNA vaccine as a booster shot could also engender excellent immunity and had less severe adverse events. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity, and significantly improved their accessibility, particularly in remote regions.
Animal models are crucial for the study of severe infectious diseases, which is essential for determining their pathogenesis and the development of vaccines and drugs. Animal experiments involving risk grade 3 agents such as SARS CoV, HIV, M.tb, H7N9, and Brucella must be conducted in an Animal Biosafety Level 3 (ABSL-3) facility. Because of the in vivo work, the biosafety risk in ABSL-3 facilities is higher than that in BSL-3 facilities. Undoubtedly, management practices must be strengthened to ensure biosafety in the ABSL-3 facility. Meanwhile, we cannot ignore the reliable scientific results obtained from animal experiments conducted in ABSL-3 laboratories. It is of great practical significance to study the overall biosafety concepts that can increase the scientific data quality. Based on the management of animal experiments in the ABSL-3 Laboratory of Wuhan University, combined with relevant international and domestic literature, we indicate the main safety issues and factors affecting animal experiment results at ABSL-3 facilities. Based on these issues, management practices regarding animal experiments in ABSL-3 facilities are proposed, which take into account both biosafety and scientifically sound data.
On page 478, Under Patients and methods section, Clinical evaluation and laboratory tests subheading, the sentence should read from "According to the latest Chinese overweight/obesity medical nutrition treatment expert consensus (2016), 16 overweight is defined as 24 kg/m 2 ≤ BMI ☐28 kg/m 2 and obesity is defined as BMI ≥28 kg/m 2 ." to "According to the latest Chinese overweight/obesity medical nutrition treatment expert consensus (2016), 16 overweight is defined as 24 kg/m 2 ≤ BMI <28 kg/m 2 and obesity is defined as BMI ≥28 kg/m 2 .
We present here a signal-on fluorescence biosensor for highly sensitive and specific detection of tumor cells with a split aptamer based on fluorescence resonance energy transfer (FRET). This sensor holds considerable potential for simple, rapid, sensitive and specific tumor cell detection in early clinical diagnosis.
Magnetic resonance imaging (MRI) of the spine is increasingly employed to detect spinal inflammation in the patients with ankylosing spondylitis (AS). AS spinal MRI activity score (ASspiMRI-a) is a novel scoring system, which was described to be reliable for assessment and quantification of acute spinal lesions of AS patients. However, the relation between ASspiMRI-a and the disease activity of AS patients is still unclear.
Objectives
The aim of this study was to determine whether ASspiMRI-a is correlate with the disease activity of AS patients through a systemic literature review with meta-analysis.
Methods
A systematic literature review was conducted using electronic databases (Medline, EMBase, and the Cochrane Library). Studies were eligible if they reported the correlation coefficients between ASspiMRI-a and disease activity scores, including Bath AS disease activity score (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Two authors performed literature selection and data extraction independently, with disagreement resolved by consensus. In the meta-analysis of correlation coefficients, data were converted into Fisher9s z values. The pooled Fisher9s z values and their 95% confidence intervals (CIs) were then computed using Review Manager 5.0 software. After that, all these results were transformed back into correlation values (r). Heterogeneity was assessed using the I2 statistic.
Results
Of 322 studies initially identified, 6 were appropriate for further meta-analysis, comprising 212 patients. Based on these studies, high heterogeneity was observed only in the meta-analysis of correlation coefficient between ASspiMRI-a on short tau inversion recovery image and BASDAI (I2 =78%, p<0.05), so it was performed using a random effects model (p<0.05, r=0.90, 95% CI: 0.79∼0.97). For the other analysis, the pooled Fisher9s z values and their 95% CIs were computed using a fix effects model. Otherwise, ASspiMRI-a on contrast-enhanced T1-weighted images was significantly associated with BASDAI (p<0.05, r=0.95, 95% CI: 0.91∼0.98). In addition, ASspiMRI-a correlated well with ESR (p<0.05, r=0.87, 95% CI: 0.79∼0.93) and CRP (p<0.05, r=0.88, 95% CI: 0.80∼0.94).
Conclusions
This systematic literature review and meta-analysis suggested ASspiMRI-a is associated with BASDAI, ESR and CRP of AS patients, so the spinal inflammation assessment by MRI might contribute to the determination of the disease activity of AS patients.
References
Goh L, Suresh P, Gafoor A, et al. Disease activity in longstanding ankylosing spondylitis: a correlation of clinical and magnetic resonance imaging findings. Clin Rheumatol. 2008, 27(4):449-55. Konca S, Keskin D, Cılız D, et al. Spinal inflammation by magnetic resonance imaging in patients with ankylosing spondylitis: association with disease activity and outcome parameters. Rheumatol Int. 2012, 32(12):3765-70.
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