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: 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.

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Objective·To investigate the expression of miR-146a in peripheral blood CD4+T lymphocytes of patients with rheumatoid arthritis(RA)and its correlation with inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Methods·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua,Shenzhen from August 2019 to July 2021 were selected.Peripheral blood mononuclear cells(PBMCs)and CD4+T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls,respectively.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-146a in peripheral blood CD4+T lymphocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α and IL-6.After transfection of the peripheral blood CD4+T lymphocytes of RA patients with miR-146a mimic,the expression of miR-146a,TNF-α and IL-6 was detected again.The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients,both before and after transfection,were analyzed by using Pearson correlation coefficient.Results·Before transfection with miR-146a mimic,the expression levels of miR-146a,TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients were significantly higher than those of healthy controls(all P＜0.001).After transfection,the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients was significantly higher,and the expression of TNF-α and IL-6 was significantly lower(all P＜0.001).The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients,both before and after transfection,was positively correlated with the expression of TNF-α and IL-6,respectively(r=0.959,P＜0.001;r=0.916,P＜0.001;r=0.971,P＜0.001;r=0.861,P＜0.001).Conclusion·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients,indicating that miR-146a may play a role in the pathogenesis of RA.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Academic exchange is an important part of cultivating young talents,which plays an important role in promo-ting knowledge dissemination,broadening academic horizons,cultivating scientific research thinking,improving innovation abili-ty,strengthening peer review,and conducting interdisciplinary cooperation.Based on the connotation and significance of academ-ic exchange,this paper analyzes the main problems faced by public hospitals in the process of academic exchange,and puts for-ward some promotion strategies,such as strengthening institutional guarantees,increasing funding support,increasing publicity efforts,and standardizing process management,creates a good academic exchange atmosphere,constructs a diverse academic ex-change platform,and provides reference for improving the quality of young talent cultivation in public hospitals.

Objective:To investigate the clinical value of the free fibula flap transplantation in repair of the defect of tibia and soft tissue with the help of augmented reality (AR) technology.Methods:From May, 2017 to May, 2019, 9 patients with tibial and soft tissue defects were treated. Before operation, CTA scan was performed on both shanks to obtain DICOM data of tibial bone defect. Images of the designed fibular flap and its blood supply model were imported into Sina software through computer virtual surgery assistant technology. With the AR technology, information of virtual fibula flap were projected onto the body surface at the donor site, and the operation was carried out under the precise positioning. In this group, the free fibular flap was harvested with an area of 6.0 cm×4.0 cm-12.0 cm×6.0 cm and the length of fibula was 6.0-13.5 cm. The free fibula flap were used to repair the tibial defect with 5.0-12.0 cm in length and soft tissue defect area at 5.0 cm×3.0 cm-10.0 cm×4.5 cm. Patients were followed-up to observe the survival of fibular flap and the functional recovery of the repaired lower limb, and evaluate the clinical effect.Results:All the fibular flaps survived without vascular crisis and without serious complications occurred at both of donor and recipient sites. After 8-12 months of follow-up, the flap was soft in texture and good in blood supply. The appearance of the repair site was not bloated. Callus began to form at the junction of fibula and tibia at 3-5 months and healed well in 8-12 months. No bone resorption, nonunion, loosening or falling off of screws were found. There was no pain in the shank of the recipient area. Patients could stand and walk freely, and the weight-bearing function was close to normal. According to Enneking system, the average score was 27 points; 7 cases were excellent and 2 cases were good.Conclusion:Application of AR technology in the repair of tibial bone defect with fibular flap transplantation has good clinical effect and has certain practical value.

Objective To meet the needs of public health emergency management in the new era, to improve the problems exposed in the public health emergency system after the outbreak of COVID-19, and to provide the government with a list of the gaps in the construction of the public health emergency system. Methods Several methods, including literature review, observation (discussion and questionnaire survey), and comparative and descriptive research, were used to conduct comprehensive analysis through the combination of induction and deduction. The evaluation questions were graded and were translated into some recognition indexes (averages). The golden section method was used for the recognition standard of evaluation problems, and U test method was used for statistical test. Results Five aspects of problem evaluation and suggestions were determined, including early warning, emergency plan, emergency management department, linkage between systems and epidemic situation judgment. The recognition indexes were 0.916, 0.905, 0.571, 1.000 and 1.190, respectively, all of which met the recognition standard, and there was no significant difference between them(P=0.357). The corresponding measures and suggestions were as follows: early warning trigger mechanism, modular emergency plan, government public health emergency agencies, collaborative emergency drill system of various industries, and expert epidemic situation judgment mechanism. Conclusion It is determined that the proposed measures to complement the weaknesses of public health emergency system in Suzhou are suitable for the locality and objectivity after the three steps of literature review, management staff discussion and professional questionnaire survey. The present study provides an objective basis for the health administrative department to propose the public health emergency system construction project to the government.

Objective:To discusses effectiveness of CTA in the classification of first plantar metatarsal artery and its application value in thumb reconstruction.Methods:Thirty-six cases who underwent thumb reconstruction with free second toe or hallucis flap between December, 2015 and December, 2018 were retrospectively analyzed. Among these cases, 22 cases were injured by machine stranding, 7 cases by heavy objects, and 7 cases were injured by rolling. Exact first plantar metatarsal arteries of all these cases were evaluated by using CTA preoperatively. And compared with intraoperative findings at the donor sites. Free first or second toe flap for thumb reconstruction were designed preoperatively based on branching pattern of first plantar metatarsal arteries.Results:The origin, course, 3-dimensional (3D) anatomical relationship with surrounding tissues and branching pattern of all these feet first plantar metatarsal arteries of 35 cases (70 feet)were well displayed in CTA images, and 1 case (2 feet) were showed poor vascular continuity and artifacts in CTA (2.78%). According to the branching pattern of first plantar metatarsal arteries, 29 cases (58 feet, 80.56%) were ramifying type, 5 cases (10 feet, 13.88%) were main trunk type, and 1 case (2 feet, 2.78%) were tiny branch type. Preoperative CTA images and intraoperative findings at the donor site of 35 cases were remarkably consistent. According to CTA images, 27 cases underwent thumb reconstruction with hallucis flap, 8 cases underwent thumb reconstruction with second toe, and 1 case of poor vascular continuity and artifacts in CTA underwent thumb reconstruction with hallucis flap eventually. All these cases were followed-up for 6-24 (average 12) months, and all reconstructed thumbs survived. The clinical outcomes of all these reconstructed thumbs were good with satisfactory appearance, sensory recovery, excellent motion. The donor feet of all cases recovered well.Conclusion:High-quality 3D images of first plantar metatarsal arteries could be obtained by CTA, allowing preoperative assessment of blood supply and planning of donor site. Therefore, success rate of reconstructed operation could be improved with low disability rate of donor site.