Postoperative UFT-/Tegafur-based Chemotherapy Versus Postoperative Radiotherapy for Early-stage Non-small Cell Lung Cancer:A Systematic Review and Network Meta-analysis

Background:Both of UFT-/Tegafur-based postoperative chemotherapy and postoperative radiotherapy have made large progress in treatment of early-stage non-small cell lung cancer.While it is unclear that,whether UFT-/Tegafur-based postoperative chemotherapy is superior to postoperative radiotherapy for early-stage non-small cell lung cancer with no direct evidence.Methods:Electronic databases(Pubmed,embase,cochrane library and clinicaltrials.gov)were searched to obtain relevant studies.This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis(PRISMA)Statement and was registered at International Prospective Register of Systematic Reviews(number CRD42018095979).Sensitive analysis was conducted by excluding overweight studies.Funnel plot and egger’s test were performed to conduct publication bias.Results:Twenty-one randomized control trials were included.Our results suggested UFT-/Tegafur-based postoperative chemotherapy could improve overall survival over postoperative radiotherapy[HR=0.69(0.59-0.80),p=0.000].But subgroup analysis about stage showed there was no significant difference between them,no matter of stage I,II and III.As to chemotherapy regime,both UFT-/Tegafur+platinum+vinca alkaloid[HR=0.68(0.56-0.82),p=0.000]and UFT-/Tegafur only[HR=0.66(0.54-0.79),p=0.000]were superior to radiotherapy.Subgroup analysis about radiotherapy delivery method and dose showed,significant improvement of chemotherapy over radiotherapy for Cobalt-60 only[HR=0.54(0.39-0.75),p=0.000],Cobalt-60 and linac[HR=0.69(0.59-0.81),p=0.000]and≥45 Gy[HR=0.64(0.54-0.75),p=0.000],but not for linac only[HR=0.78(0.60-1.03),p=0.081]and≥45 Gy[HR=0.86(0.67-1.11),p=0.241].Conclusion:UFT-/Tegafur-based postoperative chemotherapy was superior to postoperative radiotherapy for improving overall survival of early-stage non-small cell lung cancer,but it is not always so under certain circumstance,such as RT delivery method and radiation dose.Of course,it is imperative to further explore differences in specific stage,such as I A and I B.

Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes

The regeneration of sweat glands(SwGs)plays a pivotal role in the functional recovery of extensive skin wounds.Recent research has illuminated the possibility of reprogramming human epidermal ker-atinocytes(HEKs)into induced SwG cells through the ectopic expression of ectodysplasin A.However,the clinical application of this genetic manipulation approach is inherently limited.In this study,we pre-sent findings demonstrating that a combination of six compounds can effectively and speedily reprogram HEKs in culture into fully functional SwG cells.These chemically induced SwG-like cells(ciSGCs)closely resemble the morphology,phenotypes,and functional properties of human primary SwG ductal cells.Furthermore,ciSGCs can be stimulated to differentiate into mature SwG cell types in vitro.In a 3D culture system,they can also generate SwG organoids that exhibit structural and biological features akin to native SwGs.Upon transplantation into scalded mouse paw skin,ciSGCs significantly expedited cuta-neous wound healing and completely restored the structural and functional aspects of the SwGs.In con-clusion,the small molecule cocktail-directed SwG reprogramming offers a non-transgenic and controllable strategy for producing high-quality,clinical-grade SwG cells,showing immense potential for the treatment of burn patients.

Functional hair follicle regeneration:an updated review

The hair follicle(HF)is a highly conserved sensory organ associated with the immune response against pathogens,thermoregulation,sebum production,angiogenesis,neurogenesis and wound healing.Although recent advances in lineage-tracing techniques and the ability to profile gene expression in small populations of cells have increased the understanding of how stem cells operate during hair growth and regeneration,the construction of functional follicles with cycling activity is still a great challenge for the hair research field and for translational and clinical applications.Given that hair formation and cycling rely on tightly coordinated epithelial-mesenchymal interactions,we thus review potential cell sources with HF-inducive capacities and summarize current bioengineering strategies for HF regeneration with functional restoration.

Cellular rejuvenation:molecular mechanisms and potential therapeutic interventions for diseases

The ageing process is a systemic decline from cellular dysfunction to organ degeneration,with more predisposition to deteriorated disorders.Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques,such as cellular reprogramming and epigenetic regulation.The great leaps in cellular rejuvenation prove that ageing is not a one-way street,and many rejuvenative interventions have emerged to delay and even reverse the ageing process.Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies.Here,we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation,and the targeted cells and core mechanisms involved in this process.Then,we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation.Various rejuvenation methods also provide insights for treating specific ageing-related diseases,including cellular reprogramming,the removal of senescence cells(SCs)and suppression of senescence-associated secretory phenotype(SASP),metabolic manipulation,stem cells-associated therapy,dietary restriction,immune rejuvenation and heterochronic transplantation,etc.The potential applications of rejuvenation therapy also extend to cancer treatment.Finally,we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology.Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.

Sebaceous gland reprogramming with a single gene, PPARG, and small molecules

Dear Editor,Sebaceous glands(SG)contribute to 90%of the skin surface lipid production and play critical roles in regulating proper skin functions including epidermal barrier maintenance,dermal immune responses,and global body anti-microbial activities.1 Reduced sebaceous lipid has been implicated in diverse skin diseases,including scarring alopecia,inflammation,chronic itch,as well as premature aging of the skin.2 Especially,scar repair after deep burns or large-scale skin defect often leads to irreversible loss of appendages.Due to lacking SG,the regenerated tissues cannot fully recapitulate the structural and functional integrity of normal skin.Therefore,generation of expandable SG cells with developmental and lipid-producing potentials represents a promising approach for treating diseased,damaged,or aged skin with better quality of life.Recently,direct cellular reprogramming has been widely used for obtaining difficult-to-maintain human cells by cell type-specific transcription factors(TFs).