Factors affecting resolution of oculomotor nerve palsy following endovascular embolization of posterior communicating artery aneurysms / Factores que influyen en el tratamiento de la parálisis oculomotora con embolización endovascular de aneurismas comunicantes posteriores

Purpose: To investigate the effect of endovascular embolization of posterior communicating artery (Pcom) aneurysms on concomitant oculomotor nerve palsy (OMNP) and factors affecting the effect of treatment. Materials and methods: Patients with the Pcom aneurysms concomitant with OMNP were retrospectively enrolled for endovascular treatment of the aneurysms. All patients had the endovascular management. The clinical effect, degree of OMNP, size of the aneurysm, type of treatment, subarachnoid hemorrhage (SAH), and time from onset to treatment were analyzed on the resolution of OMNP. Results: Ninety-six patients with 99 Pcom aneurysms were enrolled and treated endovascularly, with the success rate of 100%. Immediately after endovascular treatment, 75 aneurysms (75.75%) got complete occlusion, and 24 (24.24%) nearly complete occlusion. Followed up for 3–18 (mean 8.52 ± 0.56) months, complete resolution of the OMNP was achieved in 63 patients (65.63%), partial resolution in 21 (21.88%), and non-recovery in the other 12 (12.50%). The degree of OMNP at onset, SAH, and time from onset to treatment were significantly (P < 0.05) correlated with the resolution of OMNP. Univariate analysis revealed that younger age of the patient, degree of OMNP at onset, presence of subarachnoid hemorrhage, and time from disease onset to treatment were significantly (P < 0.05) associated with the recovery of OMNP. Multivariate analysis revealed that the younger age, degree of OMNP at onset, and time from disease onset to treatment were significantly (P < 0.05) associated with the recovery of OMNP. Conclusion: Endovascular embolization of Pcom aneurysms concomitant with OMNP can effectively improve the OMNP symptoms, especially for patients with moderate and a shorter history of OMNP. Younger age, degree of oculomotor nerve palsy at onset, and time from onset to treatment may significantly affect recovery of oculomotor nerve palsy.(AU)

Objetivo: Investigar la eficacia de la embolización intravascular del aneurisma de comunicación posterior (Pcom) en pacientes con parálisis oculomotora (OMNP) y los factores que influyen en la eficacia. Materiales y métodos: Se analizaron retrospectivamente los datos clínicos de la terapia intravascular en pacientes con aneurismas Pcom con OMNP. Todos los pacientes recibieron tratamiento intravascular. Se analizaron los efectos de la eficacia clínica, el grado de OMNP, el tamaño del aneurisma, el método de tratamiento, la hemorragia subaracnoidea y el tiempo desde el inicio hasta el tratamiento en la regresión de OMNP.Resultados: Un total de 96 pacientes con 99 aneurismas Pcom fueron tratados con éxito. Inmediatamente después del tratamiento intravascular, 75 casos (75,75%) de aneurismas fueron completamente ocluidos y 24 casos (24,24%) casi completamente ocluidos. Durante el seguimiento de 3 a 18 meses (promedio: 8,52 ± 0,56 meses), se logró la resolución completa en 63 casos (65,63%), la resolución parcial en 21 (21,88%) y la no recuperación en los otros 12 (12,50%). El grado de OMNP al inicio, la hemorragia subaracnoidea y el tiempo de inicio a tratamiento se correlacionaron significativamente con la resolución de la OMNP (p < 0,05). El análisis univariado mostró que la menor edad del paciente, el grado de OMNP, la presencia de hemorragia subaracnoidea y el tiempo transcurrido desde el inicio de la enfermedad hasta el tratamiento se correlacionaron significativamente con la recuperación de OMNP (p < 0,05). Conclusión: La embolización intravascular del aneurisma Pcom combinada con OMNP puede mejorar eficazmente los síntomas de OMNP, especialmente en pacientes con OMNP a corto y mediano plazo. La edad temprana, el grado de parálisis del nervio oculomotor al inicio y el tiempo desde el inicio hasta el tratamiento tuvieron un efecto significativo en la recuperación de la parálisis del nervio oculomotor.(AU)

Factors affecting resolution of oculomotor nerve palsy following endovascular embolization of posterior communicating artery aneurysms.

PURPOSE: To investigate the effect of endovascular embolization of posterior communicating artery (Pcom) aneurysms on concomitant oculomotor nerve palsy (OMNP) and factors affecting the effect of treatment. MATERIALS AND METHODS: Patients with the Pcom aneurysms concomitant with OMNP were retrospectively enrolled for endovascular treatment of the aneurysms. All patients had the endovascular management. The clinical effect, degree of OMNP, size of the aneurysm, type of treatment, subarachnoid hemorrhage (SAH), and time from onset to treatment were analyzed on the resolution of OMNP. RESULTS: Ninety-six patients with 99 Pcom aneurysms were enrolled and treated endovascularly, with the success rate of 100%. Immediately after endovascular treatment, 75 aneurysms (75.75%) got complete occlusion, and 24 (24.24%) nearly complete occlusion. Followed up for 3-18 (mean 8.52±0.56) months, complete resolution of the OMNP was achieved in 63 patients (65.63%), partial resolution in 21 (21.88%), and non-recovery in the other 12 (12.50%). The degree of OMNP at onset, SAH, and time from onset to treatment were significantly (P<0.05) correlated with the resolution of OMNP. Univariate analysis revealed that younger age of the patient, degree of OMNP at onset, presence of subarachnoid hemorrhage, and time from disease onset to treatment were significantly (P<0.05) associated with the recovery of OMNP. Multivariate analysis revealed that the younger age, degree of OMNP at onset, and time from disease onset to treatment were significantly (P<0.05) associated with the recovery of OMNP. CONCLUSION: Endovascular embolization of Pcom aneurysms concomitant with OMNP can effectively improve the OMNP symptoms, especially for patients with moderate and a shorter history of OMNP. Younger age, degree of oculomotor nerve palsy at onset, and time from onset to treatment may significantly affect recovery of oculomotor nerve palsy.

[Study on liver tissue derived-extracellular vesicles regulating the osteogenic differentiation ability of mesenchymal stem cells and promoting the healing of jaw bone defects].

Objective: To explore the biological process of liver tissue-derived extracellular vesicle (LT-EV) in promoting osteogenic differentiation of mesenchymal stem cells and healing of jaw defects to provide a feasible treatment method for the clinical treatment of jaw bone defects. Methods: Enzymatic hydrolysis and differential centrifugation were used to extract LT-EV, scanning electron microscopy, Western blotting, and nanoparticle tracking analyzers were used to identify and characterize LT-EV, and further to explore the biological functions of LT-EV through proteomics and Kyoto Encyclopedia of Genes and Genomes. Flow cytometry was used to detect LT-EV plasma concentration and to calculate the plasma half-life of LT-EV. Small animal in vivo imaging system was used to detect the biological distribution of LT-EV 24 hours after injection. Six C57BL/6 mice were divided into control group and LT-EV group (3 mice in each group) by simple random sampling method. All mice underwent jaw bone defect surgery and tail vein injection every 7 days (the control group was injected with phosphoric buffer saline, LT-EV group was injected with LT-EV), micro-CT was used to evaluate the degree of mouse jaw bone healing 28 days after surgery, HE staining was used to analyze the multi-organ biosafety of LT-EV, and immunofluorescence staining was used to detect the jaw bone expression of osteogenic marker proteins in the defect area. Human jaw bone mesenchymal stem cells (hJBMSC) induced by osteogenic differentiation were treated with LT-EV (obtained from orthognathic surgery patients provided by the Department of Traumatology and Orthognathic Surgery of School of Stomatology of The Fourth Military Medical University resected normal jaw bone fragments), and the difference in osteogenic differentiation ability between the hJBMSC group and the control group (phosphate buffer saline treatment) was compared, and the in vitro bone differentiation promoting effect of LT-EV was verified through alkaline phosphatase (ALP) staining and real-time fluorescence quantitative PCR. Results: The yield of LT-EV was high, and proteomics and Kyoto Encyclopedia of Genes and Genomes showed that LT-EV contained a series of proteins that regulated cell biological functions. LT-EV injected into the tail vein could reach the mouse jaw bone defect area and promote the regeneration and repair of the jaw bone defect [the bone volume fractions of the LT-EV group and the control group were (36.06±4.20)% and (18.58±5.61)%, respectively; t=4.32, P=0.013], and had good biosafety. LT-EV could promote osteogenic differentiation of hJBMSC in vitro. Compared to the control group, ALP staining and osteogenic gene expression levels were significantly enhanced after osteogenic differentiation of hJBMSC (P<0.05). Conclusions: LT-EV exhibits a high yield, ease of acquisition, high biological safety, and excellent bone-promoting effects. It holds promise as a novel cell-free therapy strategy for regenerating craniofacial bone defects.

Exploring Recent Decreases in First Molar Sealants among US Children.

Analyses of National Health and Nutrition Examination Survey (NHANES) data suggested a significant decrease in sealant prevalence among children between 2011 to 2014 and 2015 to 2018. We explore whether this decrease could be associated with possible changes in 1) clinical sealant delivery, 2) dental materials (i.e., increased use of glass ionomer [GI] sealants resulting in an inability to detect sealant fragments that still provide preventive benefits or increased use of composite restorations leading to misclassifying sealants as restorations), and 3) examination sensitivity and specificity. We used NHANES data to estimate the prevalences of sealants, untreated caries, and restorations in ≥1 first permanent molar among children aged 7 to 10 y and used Medical Expenditure Panel Survey data to estimate the annual clinical delivery of sealants and fluoride treatments. We examined changes in outcomes between 2 periods (P < 0.05) controlling for selected sociodemographic characteristics. NHANES sealant examination quality was based on the reference examiner's replicate examinations. The adjusted prevalence of sealants decreased relatively by 27.5% (46.6% vs. 33.8%). Overall, untreated caries decreased. Untreated caries and restoration decreased among children without sealants. Annual clinical sealant delivery did not change, whereas fluoride treatment delivery increased. The decrease in sealant prevalence held when assessed for various age ranges and NHANES cycle combinations. While sealant examination specificity remained similar between the periods, sensitivity (weighted by the proportion of exams by each examiner) decreased relatively by 17.4% (0.92 vs. 0.76). These findings suggest that decreased sealant prevalence was not supported by decreased clinical sealant delivery nor increased use of composite restorations. Decreased examination sensitivity, which could be due to an increased use of GI sealants, could contribute to the decrease in sealant prevalence. The decrease in caries among children without sealants could suggest the increased use of GI sealants. However, we could not rule out that the decrease in caries could be attributable to increased fluoride treatment delivery.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Safety and efficacy of the Low-Profile Visualized Intraluminal Support stent in treating intracranial atherosclerotic stenosis.

PURPOSE: The performance of the Low-Profile Visualized Intraluminal Support (LVIS) stent deployed following balloon angioplasty is unknown in treating intracranial atherosclerotic stenosis, and this study was to investigate the safety and efficacy of the LVIS stent in treating intracranial atherosclerotic stenosis in the middle cerebral artery M1 segment. METHODS: Thirty-five patients were enrolled with 35 atherosclerotic stenoses at the M1 segment. The stenosis was about 75% in 16 patients, 80% in 15, and 90% in the rest four. The LVIS stent was used to treat these patients. RESULTS: The success rate of stenting was 97.1%. The stenting procedure was failed in one patient because of intraprocedural dissection of the stenotic (75%) segment, resulting in a 30-day periprocedural complication rate of 2.9% (1/35). Before stenting, the stenosis rate ranged 75%-90% (mean 78.9%±4.7%), and after stenting, the diameter of the stented segment was significantly (P<0.0001) increased to 1.5-3.4mm (mean 2.1±0.32mm) ranging 68.2%-100% (mean 94.0%±5.8%) of the normal arterial diameter, with the residual stenosis ranging 0-31.8% (median 4.8%, IQR 2.4%-7.3%). Follow-up was performed at 6-20 months (mean 8.5) after stenting. One patient (2.9%) had occlusion of the stented M1 segment with no symptoms, and two patients (5.7%) had slight asymptomatic instent stenosis (40%) at the M1 segment, with the instent restenosis and occlusion rate of 8.6% (3/35). CONCLUSION: The braided LVIS stent can be safely applied for treatment of intracranial atherosclerotic stenosis in the middle cerebral artery with good safety and efficacy immediately after stenting and at follow-up.

Safety and efficacy of the Low-Profile Visualized Intraluminal Support stent in treating intracranial atherosclerotic stenosis / Seguridad y efectividad del stent LVIS™ en el tratamiento de estenosis intracraneales ateroscleróticas

Purpose: The performance of the Low-Profile Visualized Intraluminal Support (LVIS) stentdeployed following balloon angioplasty is unknown in treating intracranial atherosclerotic stenosis, and this study was to investigate the safety and efficacy of the LVIS stent in treatingintracranial atherosclerotic stenosis in the middle cerebral artery M1 segment.Methods: Thirty-five patients were enrolled with 35 atherosclerotic stenoses at the M1 segment. The stenosis was about 75% in 16 patients, 80% in 15, and 90% in the rest four. The LVISstent was used to treat these patients. Results: The success rate of stenting was 97.1%. The stenting procedure was failed in onepatient because of intraprocedural dissection of the stenotic (75%) segment, resulting in a 30-day periprocedural complication rate of 2.9% (1/35). Before stenting, the stenosis rate ranged75%—90% (mean 78.9% ± 4.7%), and after stenting, the diameter of the stented segment wassignificantly (P < 0.0001) increased to 1.5—3.4 mm (mean 2.1 ± 0.32 mm) ranging 68.2%—100%(mean 94.0% ± 5.8%) of the normal arterial diameter, with the residual stenosis ranging 0—31.8%(median 4.8%, IQR 2.4%—7.3%). Follow-up was performed at 6—20 months (mean 8.5) afterstenting. One patient (2.9%) had occlusion of the stented M1 segment with no symptoms, andtwo patients (5.7%) had slight asymptomatic instent stenosis (40%) at the M1 segment, with theinstent restenosis and occlusion rate of 8.6% (3/35). Conclusion: The braided LVIS stent can be safely applied for treatment of intracranialatherosclerotic stenosis in the middle cerebral artery with good safety and efficacy immediatelyafter stenting and at follow-up.(AU)

Objetivo: Nos propusimos analizar la seguridad y efectividad de la colocación de un stentlow-profile visualized intraluminal support (LVIS TM ) tras angioplastia con balón en pacientescon estenosis ateroscleróticas intracraneales en el segmento M1 de la arteria cerebral media(ACM). Métodos: Incluimos 35 pacientes con estenosis ateroscleróticas en el segmento M1 de la ACM;la estenosis era del 75% en 16 pacientes, del 80% en 15 y del 90% en los 4 restantes. En todoslos casos el tratamiento se basó en la colocación de un stent LVIS TM . Resultados: El stent se implantó con éxito en el 97,1% de los casos; en un paciente, el procedimiento no se pudo llevar a cabo a causa de una disección del segmento estenótico (estenosisdel 75%) durante la operación, lo que supone una tasa de complicaciones perioperatorias a los30 días del 2,9%. Antes de la colocación del stent, el grado de estenosis oscilaba entre el 75 yel 90% (media [DS]: 78,9% [4,7%]). Tras el procedimiento, el diámetro del segmento en el quese había colocado el stent aumentó de forma significativa (P < 0,0001) hasta los 1,5-3,4 mm(media: 2,1 mm [0,32]), logrando un 68,2-100% (media: 94,0% [5,8%]) del diámetro normal dela arteria, y una estenosis residual del 0 al 31,8% (mediana: 4,8%; p25-p75, 2,4-7,3%). Se realizóun seguimiento de entre 6 y 20 meses (media: 8,5) tras el procedimiento. Un paciente (2,9%)presentó una oclusión asintomática del segmento M1 intervenido, y 2 pacientes (5,7%) presentaron estenosis intrastent asintomáticas leves (40%) en M1, por lo que la tasa de reestenosisintrastent y oclusión fue del 8,6%. Conclusión: El stent LVIS TM es un tratamiento seguro y efectivo para las estenosis ateroscleróticas intracraneales en la ACM.(AU)

[Untargeted metabolomics study of dexamethasone-induced congenital cleft palate in New Zealand rabbits].

Objective: To investigate the metabolic disorders in placental tissues of dexamethasone induced cleft palate mode. Methods: Twelve pregnant rabbits were randomly divided into dexamethasone group (experimental group, 8) and saline control group (4), and a certain amount of dexamethasone and saline were administered intramuscularly to the experimental and control groups respectively from embryonic days (ED) 13 to 16, and placental tissue samples were collected on day 21 of gestation. The corresponding profiles of the embryonic placental tissue samples were obtained by liquid chromatography-triple tandem quadrupole(LC-MS), and the metabolites of the embryonic placental tissues were characterized by principal component analysis among the dexamethasone-treated group with cleft palate (D-CP group), the dexamethasone-treated group without cleft palate (D-NCP group) and the control group. Results: There were significant metabolic differences among the D-CP group, D-NCP group and control group, with a total of 133 differential metabolites (VIP>1, P<0.05) involving in important metabolic pathways including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism, and galactose metabolism. The four metabolites, vitamin B6, galactose, lysine and urea, differed among the three groups (P<0.05). There were significant differences in vitamin B6 (0.960±0.249, 0.856±0.368, 1.319±0.322), galactose (0.888±0.171, 1.033±0.182, 1.127±0.127), lysine (1.551±0.924, 1.789±1.435, 0.541±0.424) and urea (0.743±0.142, 1.137±0.301, 1.171±0.457, respectively) levels among control group, D-NCP group and D-CP group (F=5.90, P=0.008; F=5.59, P=0.009; F=4.26, P=0.025; F=5.29, P=0.012). Conclusions: The results indicated that dexamethasone induced cleft palate may be highly correlated with metabolic disorders including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism and galactose metabolism.

Evaluating the Effectiveness of Digital Content Marketing Under Mixed Reality Training Platform on the Online Purchase Intention.

The purpose of this research is to investigate the effectiveness of Digital Content Marketing (DCM) on a Mixed Reality (MR) training platform environment with the consideration of online purchase intention (OPI) through social media. E-commerce today encounters several common issues that cause customers to have reservations to purchase online. With the absence of physical contact points, customers often perceive more risks when making purchase decisions. Furthermore, online retailers often find it hard to engage customers and develop long-term relationships. In this research, a Structural Equation Model (SEM) is proposed to examine the efficacy of DCM from both immediate and long-term OPI. The results examine whether adopting DCM on an MR training platform environment through social media brings positive results in OPI. Empirical research was carried out through online questionnaires collected in 2021 and 2022. A total of 374 questionnaires were qualified for data analysis in this study, conducted with IBM SPSS and AMOS. The results imply that DCM is critical to stimulating both immediate and long-term OPI. The immediate OPI is positively affected by increasing perceived value through MR in DCM. Regarding the long-term OPI, increased customer engagement with DCM under MR environment can cultivate brand trust and significantly affect the long-term OPI.

A preliminary study of peripheral T-cell subsets in porokeratosis patients with MVK or MVD variants.

Background: Porokeratosis (PK) is considered a skin-specific autoinflammatory keratinization disease. Intriguingly, four causative genes of PK are in turn arranged in mevalonate pathway, with MVD variants being the commonest followed by MVK variants in a cohort of Chinese patients. Evidence indicates that mevalonate metabolites induce trained immunity in human monocytes and regulate T cells at multiple levels. Of note, γδT cells are dually regulated by intracellular and extracellular mevalonate metabolism. Aims: To identify the possible differences in T-cell between MVK or MVD variants from PK patients. Materials & Methods: Targeted exome sequencing and exonic CNV screening were performed in 26 patients with PK. Sanger sequencing was used to validate all identified variants. Among them, 22 patients were identified with MVK or MVD variants. PBMCs from 22 PK patients and 27 normal controls (NCs) were analysed by flow cytometry for the frequencies of T cells subsets, including IFN-γ-, and TNF-α-producing T cells. Results: There were 14 mutations identified in the 26 PK patients, including 6 novel mutations (MVK: c.118_226+1337dup, c.388_392delGATATinsC, c.613A>T, c.768G>C, and MVD: c.250C>T, c.988T>G). In contrast to NCs, significantly decreased frequencies of CD8+ and Vγ9Vδ2 T cells were observed in the PK patients with MVD variants. Moreover, it was found that dysregulated secretion of pro-inflammatory cytokines by T cells in both PK patients with MVK and MVD variants. Conclusions: Our findings enriched the Human Gene Mutation Databases and showed probable differences in peripheral T cells subsets between PK patients and controls.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

[Arthroscopic-assisted fracture reduction combined with robot-navigated nail placement to treat talar neck fractures].

This study aims to explore the clinical efficacy of arthroscopic-assisted reduction combined with robot-navigated nail placement in the treatment of talar neck fractures. The clinical data of 13 patients with talar neck fracture in Xuzhou Benevolent Hospital from January 2018 to January 2021 were analyzed in the retrospective study. Among them, there were 9 males and 4 females, aged (36±12) years; there were 8 cases suffered on the right and 5 cases on the left. All patients were reset under arthroscopy and cannulated screws were placed in combination with three-dimensional navigation and positioning of orthopedic robot. The wounds and complications were observed in the postoperative follow-up. The activities of bilateral ankle dorsiflexion and plantar flexion were measured in the last follow-up. The visual analogue scale score (VAS) of pain in the affected feet before operation were compared with that at the last follow-up. The ankle and hind foot work energy scale of American Foot and Ankle Association (AOFAS) was used to assess the ankle function. The results showed that the wounds of 13 patients healed in one stage. The operation time was (95±45) min and the blood lose was (45±10) ml. All the patients were followed-up for (15.0±3.5) months. Two cases developed subtalar arthritis without talus necrosis and fracture nonunion. At the last follow-up, there was no significant difference in the dorsal extension and plantar flexion of the ankle between the affected side and the healthy side (25.8°±1.9° vs 26.2°±2.3°, 44.2°±2.7° vs 44.7°±2.8°, both P>0.05). The VAS score of pain in the affected foot at the last follow-up was 0.53±0.18, it was significantly lower than that before operation (0.87±0.29) (P<0.001). The mean AOFAS ankle and hind foot energy scale of the ankle function was 93.5 at the last follow-up. It's showed that treatment of talus neck fracture with arthroscopy assisted and robot guided nail placement is satisfactory and is worthy of clinical promotion.

[Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy].

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.