Application of internal fixation of steel-wire limited loop in early Achilles tendon rupture

Objective:To explore the clinical effect and safety of internal fixation of steel-wire limited loop in early Achilles tendon rupture.Methods:Seventy-six patients respectively with early transected and avulsed types of Achilles tendon rupture were selected and treated with internal fixation of steel-wire limited loop.The patients began to take exercise for their lower limbs through continous passive motion as early as possible after surgical repair,and the loops were removed after 3-5 months.Six months later,the condition of complications including Achilles tendon re-rupture,wound fistula,wound infection and skin necrosis,cutaneous sensation in sural nerve dominance region,time back to preinjury work or learning as well as time to physical activities were observed.One year later,the therapeutic effect was evaluated,and the maximum circumferences of bilateral legs and raptured plane circumferences of Achilles tendon were measured.Results:The wound of all patients healed well,no complications like Achilles tendon re-rupture,wound fistula,wound infection and skin necrosis occured,and the cutaneous sensation in sural nerve dominance region was normal.The mean time back to preinjury work or learning as well as to pysical activities of all patients were respectively 10 and 22 weeks.Seventy out of 76 patients(92.1%) achieved an excellent effect,and 6(7.9%) good effect.The excellent and good rate came up to 100%.The maximum circumference in the affected leg decreased to 2 mm averagely compared with the offside,while the ruptured plane circumferences of Achilles tendon in the affected side increased to 2.2 mm compared with the offside.Conclusions:Kor early Achilles tendon rupture,internal fixation of steel-wire limited loop can recover the ankle function better,return to the preinjury state in the shortest lime,and has few complications.

Measurement of serum cystatin C,creatinine clearance and urea micro-albumin as renal function evaluation indicators in cancer patients during chemotherapy with platinum

Objective:Chemotherapy drugs such as platinum may cause damage to the renal function,creatinine clearance(Ccr),as a "golden standard" indicator in clinical evaluation of renal function,was limited in application due to complicated detection steps.By detecting the expression of serum Cystatin C(Cys C),Ccr and urinary micro-albumin(UMA),this study was designed to analyze and discuss their roles and status in renal function evaluation for cancer patients before and after chemotherapy with platinum.Methods:We retrospectively reviewed 110 patients who receiving platinum-containing protocols or non-platinum-containing ones,and got the expression of Cys C,Ccr(was calculated by Cockcroft-Gault equation) and UMA,then analyzed whether there were differences for Cys C,Ccr and UMA in those patients;for patients with mildly impaired renal function(Ccr between 50-75 mL/min),whether there were differences for Cys C and UMA before and after chemotherapy with platinum.Results:There was statistical significance for Ccr,Cys C and UMA in patients who receiving platinum-containing protocols(85.01 ± 28.40) vs(76.79 ± 26.63) mL/min,(1.49 ± 0.50) vs(1.80 ± 0.84) mg/L and(14.30 ± 9.15) vs(16.90 ± 10.95) mg/L,P = 0.00,0.00 and 0.01),and no statistical significance for those receiving non-platinum-containing ones(89.45 ± 29.69) vs(86.78 ± 27.96) mL/min,(1.51 ± 0.78) vs(1.63 ± 0.73)mg/L and(17.31 ± 10.46) vs(16.59 ± 8.33) mg/L,P = 0.45,0.07 and 0.57);and there were also significant differences for Cys C for patients with mildly impaired renal function before and after chemotherapy(1.68 ± 0.55) vs(2.04 ± 0.68) mg/L,P = 0.03),while no statistical significance for UMA for the same ones(21.11 ± 10.06) vs(21.22 ± 8.81) mg/L,P = 0.93).There were statistical significance both for Cys C and UMA before and after chemotherapy in platinum-containing group,but the AUC for Ccr and Cys C is greater than that for UMA(P < 0.02).Conclusion:Cys C and UMA can both access renal dysfunction early after chemotherapy,but Cys C is more sensitive than UMA in reflecting early renal dysfunction,so Cys C can replace Ccr and become a reliable indicator in the assessment of renal function for cancer patients before and after chemotherapy especially with platinum.

Comparing Design Void Content with Actual Void Content of Laboratory Prepared Pervious Concrete

The goal of this study was to compare the predicted void content with the actual void content of pervious concrete cylinders. All pervious concrete systems are designed with a void content in mind to facilitate a specific permeability;however, due to variable placing techniques and inherent issues with the material, the actual in place void content often varies from designed. This study quantifies this difference and attempts to develop a correction factor, such that design values are more approximate to in place pervious concrete systems. The analysis included multiple mixtures with three design void contents (15%, 25%, 35%), two aggregate types (angular and rounded), and three different water-to-cement ratios (0.33, 0.37, 0.41). These samples were methodically designed to contain a desired void ratio, then casted in the laboratory, in which the compaction of each sample was controlled for consistency. Following casting, the in-place void content was determined using ASTM C1754 and compared to the predicted. The difference was then averaged to create a correction factor requiring more or less cement paste, which was used to redesign the mixtures. The new mixtures were then compared to the predicted void content. The results of this study show that initial designs can vary from 3% - 15% on average from initial designed void content and that a correction factor can be used to obtain within 3% on average of the target void ratios.

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy:China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies.In this study,we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n=3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression,which included the following variables: male patients,induction chemotherapy for newly diagnosed or relapsed disease,neutropenia,neutropenia longer than 10 days,hypoalbuminemia,central-venous catheter,and history of IFD.The patients were classified into three groups,which had low (0-10,~1.2%),intermediate (11-15,6.4%),and high risk (> 15,17.5%) of IFD.In the validation set (n=1389),the IFD incidences of the groups were ~1.4%,5.0%,and 21.4%.In addition,we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients,whereas benefits were documented in intermediate (2.1% vs.6.6%,P=0.007) and high-risk patients (8.4% vs.23.3%,P=0.007).To make the risk score applicable for clinical settings,a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established,and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD.In conclusion,an objective,weighted risk score for IFD was developed,and it may be useful in guiding antifungal prophylaxis.

Metabolism pathways of arachidonic acids:mechanisms and potential therapeutic targets

The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.

Characterization of DNA damage response deficiency in pancreatic cancer patients from China

To the editor,Pancreatic ductal adenocarcinoma(PDAC)has the worst prognosis among all common malignant solid tumors,with a 5-year overall survival(OS)rate of less than 10%[1].Few effective targets for anticancer ther-apy have been confirmed in pancreatic cancer.Recently,it was substantiated that pancreatic cancer patients carry-ing deleterious mutations of the DNA damage response(DDR)genes are more likely to benefit from platinum-based chemotherapy[2]and poly(adenosine diphosphate-ribose)polymerase(PARP)inhibitor[3].

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy

Background:CSF1R-related leukoencephalopathy,also known as hereditary diffuse leukoencephalopathy with spheroids(HDLS),is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor(CSF1R)gene mutation.Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown.Methods:In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations,we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases.Next generation sequencing was conducted for 10 probands to confirm the diagnosis.Sanger sequencing,segregation analysis and phenotypic reevaluation were utilized to substantiate findings.Functional examination of identified mutations was further explored.Results:Clinical and neuroimaging characteristics were summarized.The average age at onset was 35.9±6.4 years(range 24–46 years old).Younger age of onset was observed in female than male(34.2 vs.39.2 years).The most common initial symptoms were speech dysfunction,cognitive decline and parkinsonian symptoms.One patient also had marked peripheral neuropathy.Brain biopsy of two cases showed typical pathological changes,including myelin loss,axonal spheroids,phosphorylated neurofilament and activated macrophages.Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons.A total of 7 pathogenic variants(4 novel,3 documented)were identified with autophosphorylation deficiency,among which c.2342C>T remained partial function of autophosphorylation.Western blotting disclosed the significantly lower level of c.2026C>T(p.R676*)than wild type.The level of microtubule associated protein 1 light chain 3-II(LC3-II),a classical marker of autophagy,was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining.Conclusions:Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis.Autophagy abnormality may play a role in the disease.Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future.However,whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled.

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies:a prospective single-arm phase Ⅱ study

Post-transplantation cyclophosphamide(PT-Cy)alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation.Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting.Thus,we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease(GVHD)prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies.This single-arm phase Ⅱ clinical trial(NCT01435447)involving 31 adult patients was conducted from January 2013 to June 2018.The donor-type neutrophil engraftment rate was 100%,and the overall incidence of grade Ⅱ to Ⅳ and grade Ⅲ to Ⅳ acute GVHD was 39%and 24%,respectively.The cumulative incidence rates of chronic GVHD(35%),including moderate to severe forms(10%),were reduced compared with those of the historical group(P=0.03 and P=0.04,respectively).With a median follow-up of 18 months,the estimated 2-year overall and event-free survival was 64.8%(95%confidence interval:47.8%–86.7%)and 58.4%(95%CI:41.9%–81.7%),respectively.The 2-year cumulative incidence rate of relapse was 19.5%(95%CI:9.0%–35.8%),whereas the non-relapse mortality rate was 21.8%(95%CI:11.3%–38.1%).These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting.This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group.A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

Arsenic in the treatment of newly diagnosed acute promyelocytic leukemia:current status and future research direction

Acute promyelocytic leukemia(APL)is a subtype of acute myeloid leukemia.In past decades,intensive studies on the biology and treatment of this disease have resulted in a remarkably thorough understanding of its pathogenesis and improvement of treatment outcomes.In particular,the introduction of all-trans retinoic acid to conventional chemotherapy improved dramatically the remission and survival rates of APL patients and consequently became the major treatment modality for it.In the last decade,the groundbreaking development of arsenic further improved the survival rate of APL patients.As the most active agent in APL,arsenic directly degrades the PML-RARαfusion transcript,leading to the differentiation and apoptosis of leukemia cells and the potential eradication of APL leukemiainitiating cells(LICs),thus making the disease a potentially curable type of leukemia.More notably,the recent development of oral arsenic compounds may further enhance not only clinical outcomes but also the convenience of patients,which may dramatically change the APL clinical scenario in the near future.