Upadacitinib for axial spondyloarthritis: a meta-analysis of efficacy and safety.

To explore the effectiveness and safety of upadacitinib for managing axial spondyloarthritis. Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were applied to search randomized controlled trials (RCTs) for assessing upadacitinib treatment for axial spondyloarthritis published until January 2024. Five RCTs involving 1,246 participants were included. The upadacitinib group had significantly higher percentages of participants achieving Assessment of spondyloarthritis international society (ASAS) 20, ASAS40, ASAS partial remission, Bath ankylosing spondylitis disease activity index (BASDAI) 50, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, ASDAS inactive disease, ASDAS clinically important improvement, and ASDAS major improvement, except for Work Productivity and Activity Impairment (WPAI) absenteeism. Obvious improvements were observed in the upadacitinib group for ASDAS (CRP), BASDAI, Modified BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Canadian Spondyloarthritis Research Consortium (SPARCC) MRI spine, SPARCC MRI sacroiliac joint, Ankylosing Spondylitis Quality of Life (ASQoLS), ASAS Health Index, Bath Ankylosing Spondylitis Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Total Back Pain, Nocturnal Back Pain, WPAI overall work impairment, WPAI presenteeism, and WPAI activity impairment. Adverse events (AEs) and serious adverse events (SAEs) incidence rates showed no significant difference differ between upadacitinib and placebo groups. Subgroup analysis revealed that disease subtype and age did not significantly affect efficacy, and upadacitinib demonstrated comparable efficacy to adalimumab for axial spondyloarthritis. Upadacitinib exhibited satisfactory efficacy in treating axial spondyloarthritis, reducing disease activity and significantly enhancing patients' physical function, emotional well-being, and social engagement. This meta-analysis offers robust evidence supporting upadacitinib as a new treatment for axial spondyloarthritis patients.

Relationship between depression severity and respiratory symptoms in US adults: A national cross-sectional study.

OBJECTIVE: The relationship between depression severity and cough, wheeze and exertional dyspnoea is unclear. The aim of this study was to explore this relationship. METHODS: We used weighted logistic regression analysis and fitted curves to explore the relationship between depression severity and respiratory symptoms. In addition, we examined the relationship between depression and COPD and asthma. Stratified analyses were used to analyse specific populations. RESULTS: We weighted 10,142 subjects to reflect the entire US population. Using the population without depression as a reference, the risk of cough and asthma in the severely depressed population was 3.32 times (OR 3.324, 95% CI 1.567-7.050) and 2.84 times (OR 2.842, 95% CI 1.521-5.311) higher than that in the population without depressive symptoms, and the risk of asthma and COPD was 2.4 times and 2.6 times (OR 2.410, 95% CI 1.371-4.236; OR 2.566, 95% CI 1.236-4.921). In subgroup analyses, the correlation between depression scores and prevalence of cough and wheeze was corrected for gender level. In addition, smoking status and marital status were interaction factors between depression score and prevalence of cough. The prevalence of exertional dyspnoea by depression score was influenced by CVD. CONCLUSIONS: Depression severity was associated with respiratory symptoms, asthma, and COPD. Gender corrected the correlation between depression and cough and asthma, and depressive state was an independent risk factor for asthma and COPD. This finding provides new ideas for the management of respiratory symptoms and diseases.

3D- and 2D-QSAR models' study and molecular docking of novel nitrogen-mustard compounds for osteosarcoma.

Background: The dipeptide-alkylated nitrogen-mustard compound is a new kind of nitrogen-mustard derivative with a strong anti-tumor activity, which can be used as a potential anti-osteosarcoma chemotherapy drug. Objective: 2D- and 3D-QSAR (structure-activity relationship quantification) models were established to predict the anti-tumor activity of dipeptide-alkylated nitrogen-mustard compounds. Method: In this study, a linear model was established using a heuristic method (HM) and a non-linear model was established using the gene expression programming (GEP) algorithm, but there were more limitations in the 2D model, so a 3D-QSAR model was introduced and established through the CoMSIA method. Finally, a series of new dipeptide-alkylated nitrogen-mustard compounds were redesigned using the 3D-QSAR model; docking experiments were carried out on several compounds with the highest activity against tumors. Result: The 2D- and 3D-QSAR models obtained in this experiment were satisfactory. A linear model with six descriptors was obtained in this experiment using the HM through CODESSA software, where the descriptor "Min electroph react index for a C atom" has the greatest effect on the compound activity; a reliable non-linear model was obtained using the GEP algorithm model (the best model was generated in the 89th generation cycle, with a correlation coefficient of 0.95 and 0.87 for the training and test set, respectively, and a mean error of 0.02 and 0.06, respectively). Finally, 200 new compounds were designed by combining the contour plots of the CoMSIA model with each other, together with the descriptors in the 2D-QSAR, among which compound I1.10 had a high anti-tumor and docking ability. Conclusion: Through the model established in this study, the factors influencing the anti-tumor activity of dipeptide-alkylated nitrogen-thaliana compounds were revealed, providing direction and guidance for the further design of efficient chemotherapy drugs against osteosarcoma.

3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma.

Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds. Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models. Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4). Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q2 (0.63) and R 2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability. Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma.

Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive. Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness. Results: A causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017-1.082, P=0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783-1.129, P=0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leave-one-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings. Conclusion: This study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.

Primary biliary cirrhosis and psoriasis: a two-sample Mendelian randomization study.

Background: Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PBC and psoriasis remain poorly defined. Methods: In this study, we conducted bidirectional MR analysis to explore the causal relationship between PBC and psoriasis using four MR methods: inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results. Results: A causal relationship between the risk of PBC and psoriasis was identified, as confirmed by IVW analysis (OR: 1.081, 95%CI: 1.028~1.137, P<0.05). The other three MR methods also produced similar results. However, psoriasis did not have a causal effect on PBC risk (OR: 1.022, 95%CI: 0.935~1.118, P>0.05). The intercept of MR-Egger regression was 0.0013 (P>0.05), indicating that genetic pleiotropy did not influence the results. Additionally, the leave-one-out analysis demonstrated the robustness of our MR findings. Conclusion: This study reveals a causal relationship between PBC and psoriasis, with PBC increasing the risk of psoriasis, but not the reverse. This potential causal relationship offers a new perspective on the etiology of PBC.

Squamous cell carcinoma arising from giant porokeratosis and rare postoperative recurrence and metastasis: A case report.

RATIONALE: Giant porokeratosis is considered to be a variant of porokeratosis of Mibelli (PM) by some medical scholars. Porokeratosis can develop into several epidermal malignant tumors, such as Bowen disease and basal cell carcinoma, among which squamous cell carcinoma (SCC) is the most common. PATIENT CONCERNS: The patient was a 53-year-old man who was admitted to our hospital due to postoperative recurrence and metastasis as SCC arising from giant PM in his left leg and foot. DIAGNOSES: The pathological results are porokeratosis and well-differentiated squamous cell carcinoma. Positron emission tomography and computed tomography results show the local recurrence of the tumor with multiple lymph node metastasis. INTERVENTIONS: This patient was transferred to orthopedic surgery for amputation of the middle and lower left thigh. OUTCOMES: Follow-up for 3 months has shown no recurrence after the surgery. LESSONS: This report reminds us to pay close attention to the likelihood of giant porokeratosis. The physicians should explore all clinical possibilities to avoid misdiagnosis of this rare disease.Although the recurrence rate of SCC arising from giant PM is very low, the surgical resection region should be expanded appropriately such as the en-block resection.

En Bloc Resection and Pelvic Ring Reconstruction for Primary Malignant Bone Tumors Involving Sacroiliac Joint.

OBJECTIVE: To observe the process of sacroiliac joint invasion by primary malignant tumors of sacrum and iliac bone, and to explore the methods of surgical resection and reconstruction. METHODS: From January 2009 to November 2017, there were nine patients with primary malignant bone tumors involving sacroiliac joints, five males and four females, aged from 16 to 63 years, with an average age of 35 years. Of these there were three cases of primitive neuroectodermal tumors, three cases of chondrosarcoma, and three cases of osteosarcoma. Pelvic ring reconstruction was performed with longitudinal half sacrum, sacroiliac joint and partial iliac bone block excision and screw-rod system combined with bone grafting. RESULTS: The operation time was 155-310 min, with an average of 245 ± 55 min, and the bleeding volume was 1400-8500 ml, with an average of 3111 ± 2189 ml. Follow-up ranged from 5 to 108 months, with a median follow-up of 24 months. Three patients (33.3%) had local recurrence, three patients (33.3%) survived without tumors, and one patient had lung metastasis 2 years after operation, and survived with tumors. Five patients (55.6%) died, of which four died of lung metastasis and one died of brain metastasis. Survival analysis showed that the 3-year overall survival rate was 57%. Bone grafts did not heal in four patients, and bone grafts healed in five patients. The healing time ranged from 5 to 7 months, with an average of 6.2 months. COMPLICATIONS: one patient developed deep infection 2 months after operation; one patient had skin edge necrosis; titanium rod loosening and displacement were found in two patients with nonunion of bone graft, and no fracture of nail rod was found. The MSTS 93 functional score of nine patients ranged from 20% to 50%, with an average of 34%. CONCLUSION: The tumors around the sacroiliac joint often invade the contralateral bone by ligament, and the en bloc resection and pelvic ring reconstruction for primary malignant bone tumors involving sacroiliac joint was feasible.

Comparison of outcomes of 2 surgical treatments for proximal humerus giant cell tumors: a multicenter retrospective study.

BACKGROUND: The incidence of giant cell tumors in the proximal humerus is low. We evaluated 2 surgical treatments for giant cell tumors of the proximal humerus and postoperative upper-extremity function. METHODS: This study retrospectively analyzed the clinical data of 27 cases of giant cell tumors of the proximal humerus at 4 Chinese medical centers specializing in bone oncology collected between January 2002 and June 2015. All patients were followed up for more than 2 years. The surgical procedures performed for treatment included curettage in 14 patients and segmental resection in 13. The Campanacci grade, occurrence of pathologic fracture, surgical method, complications, and Musculoskeletal Tumor Society score were recorded for each cohort. RESULTS: The recurrence rate was 7.1% in the curettage group and 15.4% in the segmental resection group. Other postoperative complications occurred in 4 patients with segmental resection, including resorption of the osteoarticular allograft in 2, subluxation of the glenohumeral joint in 1, and prosthetic loosening and exposure in 1. A significant difference in postoperative upper-extremity function was noted between the 2 groups (P < .001). CONCLUSIONS: Postoperative upper-extremity function in the curettage group was significantly better than that in the segmental resection group. Segmental resection and reconstruction with a large segmental osteoarticular allograft were considered unadvisable. We suggest that extensive curettage should be selected to treat proximal humerus giant cell tumors as much as possible.

Investigation on the pitting of potato starch granules during high frequency ultrasound treatment.

In this paper, the pitting of potato starch granules in aqueous suspensions (1%) by high-frequency high-power ultrasound (850kHz at a power of 0.2W, 2W or 3.7W; and also 500kHz and 1MHz at a power of 2W) is reported. The number of pits per starch granules was found to be independent of the amylose content of starches, and the surface properties of starch granules as modified through SDS and ethanol washing. At 850kHz, the maximum number of pits per starch granule, for both normal and waxy starches, did not exceed 11. However, a close inspection of fractionated starch granules based on their sizes showed that there is an optimum granule size for which a maximum pit number is obtained. For example, starch granules with diameter size range of ∼15 to ∼30µm had a maximum pit number (between 10 and 20 pits per granule) when sonicated (2W, 850kHz and 30min); while sonication of small (<10µm) and very large (>45µm) granules resulted in a smaller number of pits per granule (∼5). Further, the maximum number of pits per granules is also found to be proportional to the ultrasound frequency, with values of approximately 7, 10 and 11 at 0.50, 0.85, and 1MHz, respectively. FTIR measurements did not show any breakup of starch molecules.