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Background Ulcerative colitis (UC) is a persistent immune-mediated inflammatory bowel disease characterized by chronic relapses and remissions. The management of UC remains a subject of contention, particularly as approximately half of the patients experience a complex disease progression marked by chronic activity or frequent recurrence of common UC symptoms, significantly impacting their quality of life. Objective The current landscape presents a growing array of treatment modalities for UC. This study aims to systematically compare the relative efficacy and safety of biologics and small molecule drugs in treating patients with UC. Methods Two independent researchers meticulously conducted a search for randomized controlled trials involving biologics and small molecule drugs for UC. The search encompassed PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Data, and VIP. The intervention group involved either biologics or small molecule drugs, while the control group received a placebo. The quality of the included studies was assessed using the Cochrane Risk of Bias tool and RevMan 5.4. Paired analyses and network meta-analyses were conducted using R Studio. The surface under the cumulative ranking curve (SUCRA) was employed to rank the included drugs based on each outcome indicator, providing a comparative assessment of the clinical efficacy of diverse treatments for UC. Results A total of 25 studies including 9 546 patients with ulcerative colitis and 10 intervention regimens (Filgotinib 100 mg, Filgotinib 200 mg, Upadacitinib, Tofacitinib, Etrolizumab, Adalimumab, Vedolizumab, Golimumab 50 mg, Golimumab 100 mg, Infliximab). The results of SUCRA probability ranking of clinical remission effect of each drug showed that Upadacitinib (94.1%) >Vedolizumab (85.1%) >Tofacitinib (74.3%) >Infliximab (72.7%) >Filgotinib 200 mg (51.5%) >Golimumab 100 mg (44.3%) >Golimumab 50 mg (39.3%) >Etrolizumab (38.9%) >Adalimumab (29.8%) >Filgotinib 100 mg (18.7%) >Placebo (0.7%). The results of SUCRA probability ranking of the effect of each drug on clinical response showed that Upadacitinib (98.4%) >Infliximab (84.4%) >Tofacitinib (67.2%) >Vedolizumab (58.4%) >Golimumab 50 mg (53.3%) >Adalimumab (34.6%) >Golimumab 100 mg (30.1%) >Placebo (0.4%). The results of SUCRA probability ranking of the effect of each drug on endoscopic remission showed that Upadacitinib (98.7%) >Tofacitinib (68.6%) >Filgotinib 200 mg (59.6%) >Adalimumab (55.2%) >Etrolizumab (46.0%) >Vedolizumab (45.9%) >Filgotinib 100 mg (23.4%) >Placebo (2.2%). The results of SUCRA probability ranking of the effect of each drug on mucosal healing showed that Upadacitinib (99.7%) >Tofacitinib (77.2%) >Infliximab (65.2%) >Golimumab 50 mg (46.4%) >Vedolizumab (44.4%) >Adalimumab (33.8%) >Golimumab 100 mg (31.9%) >Placebo (1.0%). The results of the SUCRA probability ranking of the risk of adverse events for each drug showed that Golimumab 100 mg (96.7%) >Golimumab 50 mg (92.1%) >Placebo (68.7%) >Tofacitinib (60.8%) >Adalimumab (60.7%) >Etrolizumab (47.2%) >Upadacitinib (42.2%) >Vedolizumab (41.3%) >Infliximab (27.0%) >Filgotinib 200 mg (6.6%) >Filgotinib 100 mg (6.2%) . Conclusion Upadacitinib demonstrated optimal efficacy in clinical response, clinical remission, mucosal healing, and endoscopic remission, and Filgotinib 100 mg demonstrating safer outcomes in terms of adverse events.

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate.ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD.MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors.ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P

In this study, a new energetic hybrid skeleton was constructed through the integration of nitropyrazole and 1,3,4-oxadiazole skeletons in a molecule. Furthermore, the energetic precursor (2), the azo-bridged compound (3), the neutral nitramine (4) and the corresponding energetic salts (5–7) were synthesized. Their physicochemical and energetic properties were experimentally and theoretically evaluated. Among the developed compounds, the azo-bridged compound (3) and dihydroxylammoinium (6) display high detonation performances (3, Dv = 8904 m/s, P = 34.47 GPa; 6, Dv = 9025 m/s, P = 34.66 GPa), moderate sensitivities (3, IS = 16 J, FS = 120 N; 6, IS = 20 J, FS = 312 N) and good densities (3, 1.87 g/cm3; 6, 1.81 g/cm3), which indicates that they have the potential to replace the traditional high-energy explosive RDX. The results show that the integration of different energetic skeletons can achieve a good balance between energy and sensitivity.

In this study, two energetic molecules with 1,4,2,5-dioxadiazine as a bridge were created by adding triazoles and pyrazoles to the oxazine skeleton. The structural characteristics, thermal behavior, and explosive properties of the obtained compounds 3,6-bis(1-nitro-1H-1,2,4-triazol-3-yl)-1,4,2,5-dioxadiazine (4a) and 3,6-bis(1-nitro-1H-pyrazol-3-yl)-1,4,2,5-dioxadiazine (4b) were investigated using experimental and theoretical techniques. To further elucidate the structure-property relationship, this study conducted calculations and analyses of quantum chemistry, such as the Hirshfeld surface analysis, the electrostatic potential (ESP) surface analysis, and the localized orbital locator (LOL) calculation. Compounds 4a and 4b have higher detonation velocities (4a: Dv ​= ​8328 ​m ​s−1; 4b: Dv ​= ​7681 ​m ​s−1) than the conventional explosive 2,4,6-trinitrotoluene (TNT; Dv ​= ​6881 ​m ​s−1) according to an energetic evaluation. Moreover, the thermal properties and sensitivities of 4a (Td ​= ​155 ​°C, IS ​= ​15 ​J, FS ​= ​288 ​N) and 4b (Td ​= ​192 ​°C, IS ​= ​20 ​J, FS ​= ​216 ​N) were greatly improved compared with the previously reported energetic furazan-1,4,2,5-dioxadiazine derivatives N,N'-((1,4,2,5-dioxadiazine-3,6-diyl)bis(1,2,5-oxadiazole-4,3-diyl))dinitramide (i; Td ​= ​106 ​°C, IS ​= ​4.5 ​J, FS ​= ​100 ​N) and 3,6-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,4,2,5-dioxadiazine (ii; Td ​= ​148 ​°C, IS ​= ​2.2 ​J, FS ​= ​116 ​N). The excellent sensitivities and acceptable detonation velocities of compounds 4a and 4b make them good candidates for potential mechanically low-sensitive explosives. These findings will enrich the further application of nitrogen heterocycle 1,4,2,5-dioxadiazine in the field of energetic materials.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow‐up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first‐line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1–95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2–97.6%) in the PP analysis as a first‐line treatment. As a second‐line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8–103.8%) in both analyses. For the FOAB regimen as a first‐line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1–101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second‐line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. Methods We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. Results There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227–5.529; OR = 1.847, 95%CI: 1.047–3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271–13.258; OR = 3.333, 95%CI: 1.068–10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070–3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023–3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361–11.308). Conclusion Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.