Allogeneic hematopoietic stem cell transplantation for patients with acute leukemia

Objective： The purposes of this study were to assess the efficacy of allogeneic hematopoietic stem cell transplantation （HSCT） for acute leukemia （AL） and analyze the factors affecting the prognosis of these patients. Methods： The clinical and follow-up data of 93 AL patients （median age, 30 years） undergoing allogeneic HSCT in Xiangya Hospital over the past 12 years were collected, and the potential factors affecting the efficacy and prognosis of allogeneic HSCT patients were determined. Results： Hematopoietic reconstitution was achieved in 90 patients. At the last follow-up, the incidences of severe acute graft versus host disease （aGvHD） and extensive chronic GvHD （cGvHD） were 14.0% and 20.0%, the 3-year cumulative incidence of transplantation related mortality （TRM） and relapse rate were 16.8%±6.1% and 21.3%±6.7%, and the estimated 3-year overall survival （OS） and disease-free survival （DFS） of the patients were 64.6%±5.4% and 56.5%±5.5%, respectively. Univariate analysis indicated that age older than 40 years, HLA mismatch, and severe lung infection within the first 100 days after transplantation were risk factors for severe aGvHD, age older than 40 years, HLA mismatch, severe lung infection within the first 100 days after transplantation, and severe aGvHD were risk factors for TRM, high-risk AL and lack of cGvHD were risk factors for relapse （all P〈0.05）. Survival estimation showed that HLA mismatch, severe lung infection occurring within the first 100 days post-transplantation, high-risk AL severe aGvHD and lack of cGvHD were risk factors associated with poor prognosis （all P〈0.05）. Further multivariate analyses revealed that severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD were independent risk factors for unfavorable outcomes （all P〈0.05）. Conclusions： Allogeneic HSCT can improve the DFS of AL patients, and severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD are independent risk factors affecting the prognosis.

Candidiasis Treatment Should Pay Attention to the Immune Changing Patients

The guideline of the Infectious Diseases Society of America (IDSA) about candidiasis is a key standard for clinical doctors to treat patients, and textbook to teach medical students. However, in the progress of clinical treatment and documents checking, the immune changing patients, who suffered candidiasis, may be mismatched to the clinical treatment guidelines. The opinion could be shown by the literature of gastrointestinal system, and respiratory system, which suffered severely fungal infection mostly, mainly connected with the outside world and inside organ systems of the human body. They could show some patients have been excess treatment, and we should pay attention to the immune changing patients.

Biomimetic multi-channel nerve conduits with micro/nanostructures for rapid nerve repair

Peripheral nervous system(PNS)injuries often lead to significant sensory and motor impairments.Traditional artificial nerve conduits,lacking anisotropic structures,have been associated with prolonged repair time and failures in nerve regeneration.This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries(PNI).A 3D oriented fibers scaffold featuring distinct radial(RFs)and longitudinal(LFs)fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques.This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures.The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance,effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold.In a rat model with a 10 mm nerve defect,the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks.These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.

Protonated-chitosan sponge with procoagulation activity for hemostasis in coagulopathy

Hemostatic materials are essential for managing acute bleeding in medical settings.Chitosan(CS)shows promise in hemostasis but its underlying mechanism remains incompletely understood.We unexpectedly discovered that certain protonated-chitosan(PCS)rapidly assembled plasma proteins to form protein membrane(PM)upon contact with platelet-poor plasma(PPP).We hypothesized that the novel observation was intricately related to the procoagulant effect of chitosan.Herein,the study aimed to elucidate the conditions necessary and mechanism for PM formation,identify the proteins within the PM and PCS's procoagulant action at the molecule levels.We confirmed that the amount of–NH3+groups(>4.9 mmol/g)on PCS molecules played a crucial role in promoting coagulation.The–NH3+group interacted with blood's multiple active components to exert hemostatic effects:assembling plasma proteins including coagulation factors such as FII,FV,FX,activating blood cells and promoting the secretion of coagulation-related substances(FV,ADP,etc)by platelets.Notably,the hemostatic mechanism can be extended to protonated-chitosan derivatives like quaternized,alkylated,and catechol-chitosan.In the blood clotting index(BCI)experiment,compared to other groups,PCS95 achieved the lowest BCI value(∼6%)within 30 s.Protonated-chitosan exhibited excellent biocompatibility and antibacterial properties,with PCS95 demonstrating inhibition effectiveness of over 95%against Escherichia coli(E.coil)and Staphylococcus aureus(S.aureus).Moreover,PCS performed enhanced hemostatic effectiveness over chitosan-based commercially agents(Celox™and ChitoGauze®XR)in diverse bleeding models.In particular,PCS95 reduced bleeding time by 70%in rabbit models of coagulopathy.Overall,this study investigated the coagulation mechanism of materials at the molecular level,paving the way for innovative approaches in designing new hemostatic materials.

A review on the pathogenesis theory of cancerous toxin from the viewpoint of system theory

In recent years,traditional Chinese medicine(TCM)has made great progress in the prevention and treatment of cancer.It has gradually revealed its characteristics and advantages in clinical practice,including alleviating clinical symptoms,prolonging survival time,decreasing the adverse effects of chemotherapy,and improving living quality.However,clinical TCM treatment of cancer lacks systematic theoretical guidance,because ancient TCM has not formed a recognized theoretical system of cognitive cancer,and there still are different opinions on the pathogenesis of cancer.Due to the complexity of cancer,the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors,such as pathogenic wind,cold,dampness,summer heat,dryness,and fire.Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin.In the 1990s,the thought of cancerous toxin was first proposed by Prof Zhou Zhongying,a TCMmaster based onmore than 60 years of clinical practice,who used“pandemic Qi(Li-Qi)is a specific pathogenic factor of epidemic disease”in Wenyi Lun(Treatise on Pestilence)for references.The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin.It holds that the cancerous toxin,a special pathogenic factor of cancer,is the key pathogenesis of the occurrence of malignant tumors.According to the pathogenesis theory of cancerous toxin,the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin,and the deficiency of the vital Qi(Zheng-Qi).Therefore,the treatment principle involves eliminating pathogenic factors,resolving cancerous toxin,and supporting the vital Qi.The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward.System theory has much in common with the concepts in the theory system of TCM,such as the universal relation theory,asking for a concrete analysis of concrete conditions,the humanism thought,and so on.This article aims to describe,review,and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.

Chinese expert consensus on the management of chimeric antigen receptor T cell therapy-associated coagulopathy

Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted.Attention should be paid to the safety of CAR-T therapy.The main adverse effects of CAR-T therapy are cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS).[4]

Synergy effects of Asperosaponin Ⅵ and bioactive factor BMP-2 on osteogenesis and anti-osteoclastogenesis

Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function.Inhibiting bone resorption and accelerating the new bone formation is a promising strategy to repair the bone defect of osteoporosis.In this study,we first systematically investigated the roles of Chinese medicine Asperosaponin Ⅵ(ASP Ⅵ)on osteogenic mineralization of BMSCs and osteoclastogenesis of BMMs,and then explored the synergistic effect of ASP Ⅵ and BS(BMP-2 immobilized in 2-N,6-O-sulfated chitosan)on bone formation.The result showed that ASP Ⅵ with the concentration lower than 10^(-4) M contributed to the expression of osteogenic gene and inhibited osteoclastic genes RANKL of BMSCs.Simultaneously,ASP Ⅵ significantly reduced the differentiation of mononuclear osteoclasts in the process of osteoclast formation induced by M-CSF and RANKL.Furthermore,by stimulating the SMADs,TGF-β1,VEGFA,and OPG/RANKL signaling pathways,ASBS(ASP Ⅵ and BS)substantially enhanced osteogenesis,greatly promoted angiogenesis,and suppressed osteoclastogenesis.The findings provide a new perspective on osteoporosis care and prevention.