Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective To investigate the frequency and dose of X-ray computed tomography (CT) medical exposure in Shantou City, and to evaluate the collective effective dose burden of residents caused by CT medical exposure. Methods The study subjects were selected using the stratified random sampling method from CT scanners in all medical institutions in Shantou City in 2020. CT application units were divided into the four tiers of municipal hospitals, district hospitals, subdistrict hospitals, and private hospitals, and 50% of the hospitals in each tier were randomly selected according to the number of hospitals in the tier. The study analyzed CT dose index results, CT scanning standard conditions, and the distribution of characteristic doses of medical exposure to evaluate the dose burden of residents in Shantou City caused by CT medical exposure. Results There were 51 CT scanners in medical institutions in Shantou City. By the end of 2020, the average number of CT scanners per million population was 9.30, and the frequency of CT medical exposure was 135.24 per 1000 population. Jinping District had the highest number of CT scanners per million population (23.2), while Chaoyang District had the lowest number of CT scanners per million population (3.6). The median and range of effective doses for different scan regions were 1.65 (0.76, 4.49) mSv in the head, 4.12 (1.90, 53.21) mSv in the chest, 5.96 (2.68, 10.25) mSv in the abdomen, and 10.30 (4.12, 12.67) mSv in the lumbar spine. By the end of 2020, the effective dose to the public in Shantou City was 6080.67 Sv·person, and the average annual effective dose per person was 1.10 mSv. Conclusion Medical exposure is the most important factor affecting resident dose burden, particularly the overuse of medical exposure examinations. CT examination is the most significant component of medical exposure causing resident dose burden. Reducing unnecessary medical exposure, ensuring the rational use of CT examination, and properly utilizing personal protective equipment are effective measures to minimize the dose burden on examinees.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

BACKGROUND:Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence.The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys.Therefore,it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE:To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS:First,the active ingredients and targets of semen cuscutae were screened in TCMSP,and the genes related to osteoarthritis were collected in the disease databases GeneCard's,OMIM and TTD.The intersected genes were taken and then subjected to a series of analyses and screened for hub genes.Through the enrichment analysis of hub genes,the pathway of semen cuscutae acting on osteoarthritis was selected.The role of hub genes was verified by molecular docking.Therefore,the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION:There were 11 active ingredients of semen cuscutae,66 intersection target genes of semen cuscutae and osteoarthritis,and 12 hub genes,including tumor necrosis factor,interleukin 1B,TP53,RAC-alpha serine/threonine protein kinase(AKT1),vascular endothelial growth factor A,matrix metalloproteinase 9,prostaglandin peroxidase 2,cystatinase 3,epidermal growth factor,peroxisome proliferator-activated receptor gamma,interleukin 10,vascular cell adhesion factor 1.After the enrichment analysis of the hub genes,the classical inflammatory pathway,nuclear factor-κB signaling pathway,was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation.Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2,sesamin with the highest affinity was selected for subsequent cell experiments,and the experimental results confirmed that sesamin,the active ingredient of semen cuscutae,could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β.To conclude,sesamin,the active ingredient of semen cuscutae,reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β,thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis.

Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

BACKGROUND:Synovitis plays a leading role in the early progression of knee osteoarthritis and is a potential early therapeutic target.However,the mechanism of synovitis remains unclear.In animal models,increased systemic iron and intracellular iron uptake can induce and exacerbate osteoarthritis,but the association with ferroptosis in synovitis remains unclear.Further studies are needed to investigate the role of ferroptosis in the development and progression of synovitis in osteoarthritis. OBJECTIVE:To investigate the role of ferroptosis mediated by glutathione peroxidase 4(GPX4)in the development of synovitis in knee osteoarthritis. METHODS:The synovial tissues of 43 patients with osteoarthritis who underwent arthroscopic or joint replacement surgery and 10 patients undergoing arthroscopic treatment of meniscal injury or ligament tear were collected and divided into three groups according to the Kellgren-Lawrence grading of X-ray images:normal control group(KLG 0,n=10),early knee osteoarthritis group(KLG 1,2,n=20)and late knee osteoarthritis group(KLG 3,4,n=23).Hematoxylin-eosin staining was used to observe the severity of synovitis in each group,and iron deposition in the synovium in each group was evaluated by Prussian blue staining.The expressions of Acyl-CoA Synthetase Long Chain Family Member 4(ACSL4),GPX4,cyclooxygenase 2 and tumor necrosis factor α in the synovium were detected by immunohistochemical staining.Western blot and immunofluorescence were used to detect the expression of ferroptosis-related proteins ACSL4 and GPX4. RESULTS AND CONCLUSION:Compared with the normal control group,iron content in synovial tissue was increased in the knee osteoarthritis groups,and iron deposition in the late knee osteoarthritis group was higher than that in the early osteoarthritis group.ACSL4 was highly expressed in the synovial tissue of knee osteoarthritis compared with the normal control group(P＜0.01),and GPX4 was lowly expressed in the synovial tissue of knee osteoarthritis(P＜0.01).The expression level of ACSL4 increased with the progression of osteoarthritis,while the expression level of GPX4 decreased with the progression of osteoarthritis.The expression of cyclooxygenase 2 in the synovium of osteoarthritis was significantly higher than that in the normal synovium,and the expression was the highest in the early stage of osteoarthritis,which was significantly different from that in the advanced stage of osteoarthritis(P＜0.01).The expression of tumor necrosis factor α in the synovium of osteoarthritis was significantly higher than that in the normal synovium,but there was no significant difference between early and late osteoarthritis groups(P＞0.05).To conclude,the deposition of iron exists in the synovial tissue of osteoarthritis and ferroptosis is involved in the occurrence and progression of synovitis in knee osteoarthritis.

BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo. OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them. METHODS:The first author searched PubMed and Web of Science databases by using"cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells"as English search terms,and searched CNKI and Wanfang databases by using"myocardial patch,biological 3D printing,myocardial"as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis. RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial patches mainly include:making myocardial patches after co-cultivation of multiple cells,improving the ink formulation and scaffold composition in biological 3D printing technology,improving the therapeutic effect of myocardial patches,suppressing immune rejection after transplantation,and perfecting the differentiation and cultivation protocols of stem cells.(4)There is no optimal cell source or method for making myocardial patches,and myocardial patches obtained from a particular cell or technique alone often do not achieve the desired therapeutic effect.Therefore,researchers need to choose the appropriate strategy for making myocardial patches based on the desired therapeutic effect before making them.