Familial primary nocturnal enuresis (FPNE) is common in clinical practice and has shown an obvious familial aggregation that is associated with genetic factors.It has been found that chromosomes 4, 8, 12, 13 and 22 are related to the inheritance of enuresis. PRDM13 and EDNRB genes are related to the pathogenesis of enuresis, but the specific functions remain unclear.FPNE accounts for a high proportion in patients with refractory enuresis.Compared with other types of primary enuresis, FPNE is not difficult to be diagnosed, as long as the related family members have enuresis, it can be diagnosed as FPNE.Due to treatment difficulties, FPNE easily lasts into adulthood, serving as a type of intractable enuresis.Therefore, early diagnosis and active intervention should be made for children with FPNE.In this review, the epidemiology, pathogenesis, diagnosis and treatment of FPNE were summarized, aiming to provide references for improving the clinical diagnosis and treatment of FPNE.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.