Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

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

ObjectiveTo investigate the clinical characteristics of leprosy-related neuritis with bullous pemphigoid after treatment of paucibacillary leprosy. MethodsThe treatment of leprosy reaction combined with bullous pemphigoid of a cured case of leprosy was analysed. ResultsFive years after standard treatment for leprosy， erythema and vesicles appeared in the limbs without obvious inducement， and the disease became more and more severe. With clinical diagnosis and pathological examination， pemphigoid was confirmed， and the patients were given hormone treatment for leprosy reaction and anti-immunotherapy， as well as symptomatic supportive treatment. ConclusionLeprosy reaction and pemphigoid are both related to immunity， but the occurrence of both at the same time is relatively rare， so in the clinical process we should attach great importance to early detection， early diagnosis and prompt treatment to prevent further harm to the patient.

Objective To identify the surface electromyographic (sEMG) characteristics of bilateral stemocleidomastoid muscles in infants with congenital muscular torticollis (CMT) after rehabilitation.Methods One hundred and twenty two infants were enrolled from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2013 and December 2015,including 63 cases receiving rehabilitation (treatment group) and 59 cases without rehabilitation (control group).The sEMG parameters of bilateral sternocleidomastoid muscles in cervical neutral,left and right rotation and stretching posture in the supine position were retrospectively collected before and after treatment/follow-up;and the root mean square (RMS) was analyzed.Results Before treatment,the RMS values of the affected side in cervical neutral position,cervical rotation and stretching posture were significantly lower than those of the unaffected side in both groups(t=15.758 and 11.950,4.871 and 4.746,4.142 and 4.318,P＜0.01).In the follow-up for control group,the RMS values of the affected side in cervical neutral position,cervical rotation and stretching posture were significantly lower than those of the unaffected side (t=10.692,2.198 and 3.239;P＜0.01,=0.03 and ＜0.01).In the treatment group there were no significant differences in the RMS values in cervical neutral position,cervical rotation and stretching posture between affected side and unaffected side after treatment(t=1.647,1.090 and 0.136,P=0.10,0.28 and 0.89).Conclusion Rehabilitation reduces the difference of the RMS values between the affected and unaffected sternocleidomastoid muscles in infants with CMT.

Objective To analyze the effect of haploidentical hematopoietic stem cell transplantation (HID-HSCT) on high-risk acute lymphoblastic leukemia (ALL),and to explore the influence of minimal residual disease (MRD) before transplant on the outcomes.Methods A retrospective analysis was performed on 39 high risk ALL patients receiving HID-HSCT in our hospital from Jan.2013 to Jan.2018.The clinical features,stem cell engraftment,complications,survival and recurrence were compared between patients with pretransplant MRD + and MRD-.Results All the 39 patients presented with successful engraftment.The overall survival (OS) was 54.67％;the disease free survival (DFS) was 40.96％;the incidence rate of acute graft versus host disease (aGVHD) was 53.8％,including 23.1％ Ⅱ-Ⅳ degree aGVHD and 2.6％ Ⅲ-Ⅳ degree aGVHD.There was no significant difference in stem cell engraftment,GVHD,cytomegalovirus infection and hemorrhagic cystitis between MRD + and MRD-patients.DFS and OS in MRD + patients were significantly lower than those in MRD-patients;the cumulative RR rate increased significantly,and there was no significant difference in cumulative TRM.Conclusion HID-HSCT was an effective method to treat high-risk ALL,but MRD + patients had high recurrence rate and poor prognosis.Strategy adjustment should be considered to reduce tumor residual and the transplantation strategy should be optimized for these kinds of high risk patients,so as to improve long-term outcomes.

Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.

Objective: To explore the effects of miR-124-ROCK1 signal pathway in the damages of glomerular endothelial cells (GEnCs) induced by high glucose. Methods: Rat glomerular endothelial cells were cultured in different glucose concentrations: normal control group (NG: 5.5 mmol/L), high glucose group (HG: 30.0 mmol/L), and cells were treated with ROCK1 inhibitor Y27632, miR-124-3p mimic, miR-124-3p inhibitor. The expressions of ROCK1 activity, cell apotosis and tight junction proteins were detected by Western blot. The cell tight junction protein ZO-1 in those groups were assessed by laser scanning confocal microscope. Results: High glucose significantly decreased miR-124 expression (P<0.01), ROCK1 activity (P-MYPT1/MYPT1), and cell apoptosis (Cleaved-Caspase3/pro-Caspase3) were found increased while the tight junction proteins ZO-1and Occludin were found decreased in these cells (P<0.05 all P<0.01), However, when pretreated cells with ROCK1 inhibitor Y27632, these injuries were significantly reversed. In cells transfected with miR-124-3p mimic, p-MYPT1/MYPT1 was decreased. p-MYPT1/MYPT1 was however increased in cells transfected with miR-124-3p inhibitor (P<0.05), indicating that miR-124 could directly inhibit ROCK1 activity. The increased ROCK1 activity and apoptosis, as well as the decreased tight junction proteins induced by high glucose were significantly suppressed as miR-124-3p mimic transfected in GEnCs. Conclusions According to our experiments, high glucose suppressed miR-124 in glomerular endothelial cells, consequenctly activating ROCK1 activity to damage endothelial cells. MiR-124 overexpression could ameliorate these damages induced by high glucose, suggesting that miR-124 might be a new therapeutic target to prevent glomerular endothelial cells injuries in diabetic nephropathy.

A method was developed for the rapud screenung and confurmatuon of 18 perfluorunated compounds ( PFCs) and 21 precursors un fush muscle by solud phase extractuon and luquud chromatography coupled wuth quadrupole/exactuve orbutrap mass spectrometry (LC-Q Exactuve Orbutrap MS). In thus method, the sample was furstly extracted wuth acetonutrule-water (90∶10, V/V), cleaned-up by solud-phase extractuon usung Oasus PRuME HLB column. Then, 39 target compounds were separated on a BEH C18(2. 1 mm×100 mm, 1. 7 μm) column, and the background unterference caused by LC system was elumunated by a short C18 HPLC column located between the muxer and the auto sampler. In the process of quantufucatuon and qualufucatuon, a full MS/dd-MS2 experument was adopted un mass spectrometry acquusutuon, accompanued wuth the full scan MS date for quantufucatuon, as well as the date dependent MS2 product uon spectra for qualufucatuon. The mass accuracy error was less than 3×10-6, and the calubratuon curves were lunear well wuth correlatuon coeffucuent over 0. 99. The lumuts of detectuon ranged from 0. 02 to 0. 50 μg/kg. The average spuked recoverues for 39 target compounds were between 61 . 7% and 122 . 0%, wuth relatuve standard deruvatuons ( RSDs ) from 6 . 9% to 18 . 8%. The developed method was successfully applued to the sumultaneous determunatuon of 18 PFCs and 21 precursors un fush muscle wuth satusfactory results.

Objective: To identify Aconitum pendulum Busch. and Aconitum kongboense Lauener. Methods: Aconitum pendulum Busch. and Aconitum kongboense Lauener were identified by microscopical identification and TLC. And the contents of aconitine in the two herbs were determined by HPLC. Results:Microscopical identification showed they were different from each other, and aconitine was used as the reference component. Using the solution consisting of hexane ∶ethyl acetate ∶diethylamine (10 ∶6 ∶0. 8) as the developing solvent, the compositions in the two herbs were different in TLC. The content of aconitine in Aconitum pendulum Busch was 0. 71 mg· g-1 , while that in Aconitum kongboense Lauener was only 0. 03 mg·g-1 . Conclusion:Aconitum pendulum Busch. and Aconitum kong-boense Lauener Identified by microscopical identification, TLC and HPLC,SHOW NOTABLE differences between them, and Aconitum kongboense Lauener should not be used as Aconitum pendulum Busch.

Objective To evaluate the safety and efficacy of Voriconazole on invasive fungal infections in very elderly patients.Methods Clinical data of 24 very elderly patients with invasive fungal infections who had sought treatment at the Department of Geriatrics of our hospital from April 2013 to April 2014 were retrospectively investigated.The classifications and quantities of fungi,accompanying symptoms,adverse reactions,blood tests,and liver and kidney function indicators were recorded and analyzed before and after treatment.Results Each of the 24 cases was found to have been infected with one or more of 17 fungal strains belonging to the genus of Candida.The rate of complete fungal elimination after treatment was 70％ (12/17).Of the 24 cases,5 achieved a full recovery(20.8 ％),10 (41.7 ％) had significant improvement,5 (20.8 ％) had some improvement,and 4 cases(16.7％)showed no therapeutic benefits,with a total effectiveness rate of 62.5 ％.There was no significant difference in liver and kidney function before and after treatment(P＞0.05).A transient increase in serum creatinine occurred in 1 case and defective vision in another patient during Voriconazole treatment.Conclusions The incidence of invasive fungal infections is high in very elderly patients,with Candida as the main pathogen.Voriconazole is effective in treating invasive fungal infections in very elderly patients,and close monitoring of liver and kidney function is required during voriconazole treatment.