Navigating therapeutic challenges in VEXAS syndrome: exploring IL-6 and JAK inhibitors at the forefront.

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.

Experimental study of energy­absorbing and support characteristics of glass microsphere-filled steel tube columns under uniaxial compression.

An innovative energy-absorbing and bearing structure was proposed, which incorporated the coupling of glass microspheres with a metal tube. Glass microsphere-filled steel tube (GMFST) column, consisting of external steel tube and inner glass microspheres, was expected to give full play to the energy-absorbing and load-bearing capacities of the particle while restricting particle flow from collapsing, thereby enhancing the overall structural strength. Four groups of steel tubes and the GMFST specimens were designed and subjected to axial compression tests at four different loading rates to investigate the performance of the structure. These tests aimed to analyze the deformation mode, mechanical response, and energy absorption capacity of the GMFST columns under quasi-static to low-speed compression conditions. The results indicated that the deformation process and failure mode of GMFST columns were similar to those of hollow steel tubes, albeit with a different post-buckling mode. Filling the steel tubes with glass microspheres reduced the load fluctuation range, moderated load-displacement curves, and exhibited a strain rate strengthening effect. The GMFST columns demonstrated superior energy absorption capacity, with significant increases in crush force efficiency, the averaged crush force, and the total absorbed energy, particularly in terms of subsequent support capacity. The load-increasing reinforcement properties enabled GMFST columns to overcome the limitations associated with the unstable post-buckling path of energy­absorbing damping structure, exhibiting outstanding load-bearing performance and stability in the later stages. The results provided valuable guidelines for designing and engineering high-performance GMFST columns, serving as a new type of energy-absorbing and supporting structure.

Whole-genome resequencing reveals molecular imprints of anthropogenic and natural selection in wild and domesticated sheep.

The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds, African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group, while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function. Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation, energy metabolism, and growth development. Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30 domesticated sheep breeds. The IFI44 c. 54413058 C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.

Accuracy of Implant Placement Guided with Surgical Template: An In Vitro and In Vivo Study.

This study evaluated the accuracy of implant placement with surgical-template guidance both in vitro and in vivo. Virtual surgical planning was performed based on the data from CBCT scans and an intraoral scanner. Surgical templates were designed according to the planned implants and manufactured with stereolithography. In vitro, 60 implants were placed in 15 resin models. In vivo, 74 implants were placed in 54 patients. The implants were scanned with CBCT postoperatively. Implant accuracy was evaluated by measuring the following parameters: central deviation at the apex and shoulder, horizontal deviation at the apex and shoulder, vertical deviation at the apex and shoulder, and angular deviation. There were statistically significant in vitro and in vivo deviations for all parameters, and the implant deviations in vivo were significantly greater than those in vitro. When using a mucosa-supported template, horizontal deviations at the apex were significantly greater than when a teeth-supported template was used. Within the limitation of the study design, inaccuracy existed in implant placement guided with a surgical template. More studies are needed to investigate the value of the procedure in future.

Dilation of the cystic duct confluence in laparoscopic common bile duct exploration and stone extraction in patients with secondary choledocholithiasis.

BACKGROUND: Many options exist for the management of cholelithiasis and secondary choledocholithiasis. Among them, laparoscopic common bile duct exploration (LCBDE) with choledocotomy followed by laparoscopic cholecystectomy has gained popularity. However, efforts should be made to ensure minimally invasive or noninvasive management of the common bile duct (CBD). The purpose of this study was to explore the clinical experience of non-invasive surgical modality, i.e., laparoscopic transcystic dilation of the cystic duct confluence in CBD exploration (LTD-CBDE), including feasibility, safety, adverse events, and incidence. METHODS: In this retrospective analysis, 68 patients were offered the LTD-CBDE technique from December 2015 to April 2018 based on patient's own intention. During the surgery, the cystic duct confluence was dilated with separation forceps and/or a columnar dilation balloon. Subsequently, CBD exploration and stone extraction were performed with a choledochoscope. The entrance of the CBD was covered with a cystic duct stump wall and was subjected to primary closure at the end of surgery. RESULTS: Forty-nine females and 19 males with cholelithiasis and secondary choledocholithiasis were included. The mean age was 53 years old (18 to 72 year). Of these patients, 62 (91.2%) were successfully treated with the LTD-CBDE technique, and bile leakage was observed in 3 patients (4.4%). The mean operation time was 106 min, and the mean hospital stay was 5.9 days. Among the other 6 patients, 3 were converted to open cholecystectomy due to severe fibrosis, unclear anatomical structure at Calot's triangle (n = 2) or Mirizze syndrome (n = 1); LCBDE was performed in 3 patients due to cystic duct atresia (n = 2) and low level of flow from the gallbladder duct into the CBD (n = 1). These patients had a smooth postoperative course. In total, 43/68 of the patients presented no radiological evidence of retained CBD stones at the postoperative follow-up (40 patients treated with LTD-CBDE) 1 year later. CONCLUSIONS: The current work suggests that LTD-CBDE for the management of cholelithiasis and secondary choledocholithiasis is a feasible, safe and effective technique with a low complication rate. LTD-CBDE offers another alternative for surgeons to treat patients in similar scenarios. However, additional randomized, controlled studies are needed to demonstrate its efficacy, safety, and impact on CBD stenosis.

[Expression of CysLTR-1 and CysLTR-2 in adenoid tissues from children with adenoid hypertrophy].

OBJECTIVE: To examine the expression of cysteinyl leukotriene receptor-1 (CysLTR-1) and cysteinyl leukotriene receptor-2 (CysLTR-2) in the adenoid tissues from children with adenoid hypertrophy (AH) and to explore the role of leukotrienes in the pathogenesis of AH. METHODS: Sixty children with AH who were treated by adenoidectomy and/or tonsillectomy were classified into two groups: simple AH and AH plus allergic rhinitis (n=30 each). Twenty children who underwent tonsillectomy due to recurrent purulent tonsillitis were selected as the control group. The expression of CysLTR-1 and CysLTR-2 in the excised tonsil and/or adenoid tissues was determined by immunofluorescence histochemical labeling and integrated optical density measurement. RESULTS: The expression of CysLTR-1 and CysLTR-2 in the adenoid and tonsil tissues increased significantly in both the simple AH group and AH plus allergic rhinitis group compared with the control group (P<0.01). The expression of CysLTR-1 and CysLTR-2 in the AH plus allergic rhinitis group increased more significantly compared with the simple AH group (P<0.01). CONCLUSIONS: CysLTR-1 and CysLTR-2 are highly expressed in the adenoid tissues from children with AH, suggesting that leukotrienes are involved in the pathogenesis of AH.

Comparison of long non­coding RNAs, microRNAs and messenger RNAs involved in initiation and progression of esophageal squamous cell carcinoma.

Traditionally, cancer research has focused on protein­coding genes, which are considered the principal effectors and regulators of tumorigenesis. Non­coding RNAs, in particular microRNAs (miRNAs) and long non­coding RNAs (lncRNAs), have been widely reported to be important in the regulation of tumorigenesis and cancer development. However, to the best of our knowledge, investigation of the expression profiles of lncRNAs and a comparison of the involvement of lncRNAs, miRNAs and messenger RNAs (mRNAs) in esophageal tumorigenesis and development have not previously been performed. In the current study, intrinsic associations among the expression profiles of lncRNAs, miRNAs and mRNAs from normal esophageal tissues and those from cancer tissues were investigated. Oligonucleotide microarrays were used to detect the expression profiles of the three types of RNA in the canceration processes of human esophageal squamous cell carcinoma (ESCC) tissues. It was demonstrated that the different RNAs exhibit associated patterns of expression among normal esophageal epithelium, low­grade intraepithelial neoplasia (LGIN), high­grade intraepithelial neoplasia (HGIN), and carcinoma tissues, particularly in the critical period of canceration (HGIN to ESCC). Furthermore, the results indicated a high level of similarity in the potential function of lncRNAs, miRNAs and mRNAs in the processes of ESCC development. In the current study, a first generation atlas of lncRNA profiling and its association with miRNAs and mRNAs in the canceration processes of ESCC were presented.

[Effects of "warmth-producing needling for removing obstruction" on hippocampal morphological changes and learning-memory abilities in vascular dementia rats].

OBJECTIVE: To observe the effects of "Warmth-producing Needling for Removing Obstruction" (WPNRO) on the pathomorphological changes of brain and learning-memory abilities in vascular dementia (VD) rats. METHODS: A total of 50 Wistar rats were randomly divided into normal control, model, medication, needle-twirling, and WPNRO groups, with 10 cases in each group. VD model was established by repeated cerebral ischemia-reperfusion via repeated occlusion of the bilateral common carotid arteries under anesthesia (3% embutal 40 mg/kg, i.p.). "Dazhui" (GV 14), "Baihui"(GV 20) and "Shuigou"(GV 26) were punctured with filiform needles and stimulated with twirling technique and WPNRO technique respectively and continuously for 1 min. Animals of medication group were fed with Nimodipine (0.0108 g/kg). The treatment was conducted once daily continuously for 15 days. The rats' learning and memory results were detected respectively with step-down avoidance test in the first 6 days' training and 24 h later. At the end of experiments and after decapitation, the right brain was taken, cut into sections (5 microm) and stained with H & E method for observing structural changes of hippocampus. RESULTS: 1) Behavior reactions: compared with control group, the latency for finding the safe platform and the times of error in model group increased significantly, and compared with model group, both latencies and times of error in WPNRO, needle-twirling and medication groups decreased considerably (P < 0.05, 0.01). In comparison with needle-twirling group, both latencies and times of error in WPNRO group were significantly fewer (P < 0.05, 0.01), and no significant differences were found between WPNRO and medication groups in these two indexes (P > 0.05). It indicated that acupuncture particularly WPNRO could improve both learning and memory abilities in VD rats. 2) Structural changes of neurons in CA1 region of hippocampus: in normal group, the neurons arranged in order and closely, and were normal in the structure; in model group, the neurons arranged obviously in disorder, had karyopyknosis and hyperplasia in glial cells and decreased in the number. In WPNRO group, no evident cellular karyopyknosis or hyperplasia of glial cells was found, and the structure and number of cells were close to those of normal group. In acupuncture and medication groups, fewer neurons, cellular karyopyknosis and hyperplasia of more glial cells were found. CONCLUSION: "Warming-producing Needling for Removing Obstruction" can significantly relieve cerebral ischemia induced disturbance of learning and memory and lessen structural injury of hippocampal neurons in rats.