Chronic mucocutaneous candidiasis (CMC) is an infectious phenotype characterized by recurrent or persistent infections caused by Candida species that affect the skin, nails, oral, and genital mucosae for a duration exceeding six months. Current research suggests that CMC is an immunodeficiency disease with a complex pathogenesis. Patients with CMC have various defects in nonspecific and/or specific immunity against Candida infection, resulting in the inability of patients to defend themselves against Candida infection. CMC can be stratified into primary CMC and secondary CMC based on etiology. Primary CMC is often associated with genetic mutations leading to immunodeficiencies in T helper cell 17 and interleukin-17, whereas secondary CMC is frequently linked to factors such as human immunodeficiency virus infection, diabetes mellitus, and immunosuppressive therapy. Primary CMC typically manifests as Candida infections, with distinct genetic mutations often correlating to varied concomitant symptoms. Secondary CMC may present with not only superficial mucosal Candida infections and manifestations of the underlying primary disease but also with invasive fungal infections. Diagnosing CMC requires an integration of medical history and clinical presentation, supplemented by the outcomes of auxiliary diagnostic procedures, including microscopic examination of fungal smear, fungal culture, immunological testing, and genetic sequencing and analysis. Furthermore, confirming primary CMC requires exclusion of the aforementioned secondary factors. At present, antifungal drugs such as triazoles, echinocandins, and polyenes are the main treatment for CMC. Moreover, immunotherapy with biologics such as Janus kinase (JAK) inhibitors provides more options for the clinical treatment of patients with CMC. Gene therapy also has potential clinical application value. In this review, we discuss the etiologies, pathogenesis, clinical manifestations, diagnosis, and treatments of CMC, aiming to provide a reference for the clinical diagnosis and treatment of CMC.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To investigate the anatomical basis for the preparation of the profunda artery perforator flap (PAPF) in the posteromedial femoral region and its application in the reconstruction of oral and maxillofacial defects.Methods:Six lower limbs of Chinese adult cadavers were micro-surgically dissected. CT angiography (CTA) data of bilateral lower limbs of 6 patients was also collected retrospectively. The number, external diameter, pedicle length, and distribution of perforators in the posteromedial femoral region were recorded from the specimens and CTA data. Meanwhile, 10 patients with oral squamous cell carcinoma in the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University from August 2018 to June 2021 were treated with the PAPF. At each follow-up, contour and function of recipient and donor site, as well as swallowing and speech function were evaluated.Results:A total of 19 profunda artery perforator were identified in 6 lower limb specimens. The outer diameter at the beginning of the source artery was (2.34±0.25) mm and the total length of the pedicle was (11.12±1.06) cm. CTA data analysis of 12 legs identified 15 perforators of profunda artery in the posteromedial region. Eleven perforators were septocutaneous, including 2 perforators with a common trunk, while the remaining 4 perforators were musculocutaneous. As for different patterns of perforators (septocutaneous perforators, musculocutaneous perforators and perforators with a common trunk), the longitudinal distance to the pubic tubercle was (19.95±2.43), (21.84±2.54) and (19.48±0.55) cm respectively. The horizontal distance to the posterior edge of gracilis was (3.54±1.10), (3.72±0.30) and (3.85±1.48) cm, respectively. The initial diameters of perforators was (2.4±0.4), (2.6±0.6) and 1.9 mm respectively. Ten cases of the profunda artery perforator flaps survived successfully after operation. The flap sizes ranged from 8 cm×6 cm to 12 cm×7 cm. The patients were evaluated at 1, 3 and 6 months, and with 6 months interval ever since. During the follow-up, the shape of the recipient site was ideal, and the swallowing and language functions were not significantly affected. There was only linear scar in the donor area, and the function of the thigh was basically normal.Conclusions:PAPF possessed a good anatomic stability, suitable vascular pedicle length and diameter, minor influence to the donor area, sufficient amount tissue with good quality. It is an ideal choice for head and neck reconstruction.

Objective To explore the role and mechanism of tumor necrosis factor ligand -related molecule 1A (TL1A) in chronic experimental colitis associated intestinal fibrosis .Methods The model of chronic experimental colitis-associated intestinal fibrosis was induced by dextran sodium sulfate (DSS).The mice with high TL1A (L-Tg) expression in lymphoid cells and wild -type mice with the same genetic background were divided into wild type control group, wild type DSS group, transgenic control group and transgenic DSS group.The changes of body mass, length of colon, disease activity index (DAI) and colonic pathological score were compared among different groups .The degree of colonic inflammation was evaluated by Hematoxylin -Eosin (H-E) staining.The degree of intestinal fibrosis was assessed by Masson staining and Sirius red staining .The expression of vimentin, αsmooth muscle actin ( α-SMA), type Ⅰ collagen, Ⅲ collagen and transforming growth factor-β1 ( TGF-β1 ) /Smad3 in colon tissue was examined by immunohistochemistry .T test was performed for statistical analysis.Results The body mass of the transgenic DSS group decreased by (9.6 ± 1.8)％, which was more than wild-type DSS group (6.2 ±1.3)％, the difference was statistically significant (t =3.751, P <0.01).The DAI score and colonic pathological score of transgenic DSS group were both higher than those of wild-type DSS group (7.33 ±0.58 vs.6.00 ±1.00, and 14.00 ±1.05 vs.11.75 ±0.50, respectively), and the differences were statistically significant (t =2.818 and 4.739, both P <0.05).The results of Masson staining and Sirius red staining showed aggravation of intestinal fibrosis .The results of immunohistochemical staining showed that the cumulative positive absorbance values of vimentin , α-SMA, TGF-β1 and Smad3 of wild-type DSS group were lower than those of transgenic DSS group (0.650 ±0.050 vs. 0.800 ±0.020, 0.390 ±0.040 vs.0.600 ±0.040, 0.550 ±0.040 vs.0.730 ±0.040, 0.590 ±0.020 vs. 0.830 ±0.040), and the differences were statistically significant (t =6.823, 9.093, 7.794 and 10.390, all P <0.01).Conclusion TL1A may promote the proliferation and activation of fibroblasts through TGF -β1 /Smad3 pathway, leading to the genesis and development of experimental colitis associated intestinal fibrosis .

Objective:To investigate the induction of tanshinoneⅡA (TanⅡA) on the differentiation of human placenta-derived mesenchymal stem cells (hPDMSCs) into cardiomyocytes, and to provide an experimental basis for TanⅡA as a cardiomyocyte differentiation inducer.Methods:The hPDMSCs were treated with different concentrations of TanⅡA (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0mg·L-1) , and the nontoxic dose of TanⅡA (0.1mg·L-1) was screened by MTT assay for experiment.The hPDMSCs were divided into control group, 5-aza induction (10μmol·L-1) group, and TanⅡA induction (0.1mg·L-1) group.After culture for 20d, the expressions ofα-sarcomeric actin (α-SCA) in the cells in various groups were detected with immunohistochemistry;the positive expression rates of cardiac troponin I (cTnI) in the cells in various groups were detected with immunofluorescence, and the differentation rates of cardiomyocytes were calculated.The expression levels of GATA-binding protein 4 (GATA4) , atrial natriuretic factor (ANF) , cTnI, glycogen synthase kinase-3β (GSK-3β) andβ-catenin in the cells were detected with Western blotting method.Results:The biological characteristics of hPDMSCs accorded with the mesenchymal stem cells.The MTT results showed that when the concentration of TanⅡA was more than 0.1mg·L-1, the cell survival rates were decreased with the increase of concentration;the cells in control group showed a rapid growth trend before 12d, and the proliferation activities of the cells began to decrease on the 12th day.Compared with control group, the cell activities in 5-aza induction group and TanⅡA induction group were significantly decreased (P＜0.05) .The immunohistochemistry staining results showed that the cells in control group didn't expressα-SCA, and the cells in 5-aza induction group and TanⅡA induction group expressedα-SCA, especially in TanⅡA induction group.Compared with control group, the expression levels of GATA4 (t5-aza=2.937, P5-aza＜0.05;tTanⅡA=4.769, PTanⅡA＜0.05) , ANF (t5-aza=3.728, P5-aza＜0.05;tTanⅡA=5.912, PTanⅡA＜0.05) , cTnI (t5-aza=3.623, P5-aza＜0.05;tTanⅡA=7.153, PTanⅡA＜0.05) and GSK-3β (t5-aza=2.995, P5-aza＜0.05;tTanⅡA=5.420, PTanⅡA＜0.05) proteins in the cells in 5-aza induction group and TanⅡA induction group were significantly increased, and the expression levels ofβ-catenin (t5-aza=2.985, P5-aza＜0.05;tTanⅡA=6.951, PTanⅡA＜0.05) protein were significantly decreased;compared with 5-aza induction group, the expression levels of GATA4, ANF, and GSK-3βproteins in TanⅡA induction group were increased (P＜0.05) .Conclusion:TanⅡA can induce the differentiation of hPDMSCs into cardiomyocytes, which has better effect than 5-aza, and its mechanism may be related to inhibiting the Wnt/β-catenin signaling pathway.

Objective To investigate the clinical efficacy of laparoscopic-assisted linea alba reconstruction for postpartum diastasis recti.Methods The retrospective cross-sectional study was conducted.The clinical data of 14 patients with postpartum diastasis recti who were admitted to Ruijin Hospital of Shanghai Jiaotong University School of Medicine between June 2016 and June 2018 were collected.Patients underwent laparoscopic-assisted linea alba reconstruction.Observation indicators:(1) intra-and post-operative recovery situations;(2) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative long-term complications,diastasis recti and umbilical hernia recurrence up to September 2018.Measurement data with normal distribution were represented as (x)±s and measurement data with skewed distribution were described as M (P25,P75).Results (1) Intra-and post-operative situations:14 patients underwent successful laparoscopic-assisted linea alba reconstruction and 8 complicated with umbilical hernia area of (6± 3) cm2 were sutured and closed.The mesh area,operation time,visual analogue score for pain at the first day after operation,time of postoperative drainage-tube removal and duration of postoperative hospital stay were respectively (214±26) cm2,(74 ± 14) minutes,3.7 ± 0.6,(3.3 ± 0.7) days and (4.1 ± 1.2) days.No patient required administration of analgesics and had postoperative complication.(2) Follow-up:14 patients were followed up for 17 months (5 months,21 months).During the follow-up,1 patient returned visit at postoperative day 10 due to surgical incision drainage and cured after dressing change.The other patients had no complications,without diastasis recti and umbilical hernia recurrence.Conclusion Laparoscopic-assisted linea alba reconstruction for postpartum diastasis recti is safe and effective.

Objective To evaluate the corneal wound quality of different corneal lamellar-cut depths with the femtosecond laser for fem-tosecond laser-assisted lamellar anterior keratoplasty so as to provide theoretical basis for the appliation of femtosecond laser.Methods Full lamellar cuts were made on 20 human cadaver corneas through femtosecond laser.The 20 human cadaver corneas were divided into 5 groups according to the relative cutting depth which means ratio of the actual cutting depth and the central cornea thickness of 17% to 21%(100 μm,n =3),31% (n =5),35% (n =5),38% to 40% (n =4),and 45% to 48% (n =3).Scanning electron microscopy images of the cap and bed surfaces were graded for ridge and roughness with a scale of 1 to 5 point (1 =best,5 =worst).And the graft-host match was evaluated by photography and optical coherence tomography in a simulated procedure.Results The ridge scores was correlated with the rela-tive cutting depth (P =0.000 24,R =0.73).The 17% to 21% group had the shallowest cutting depth and the fewest ridges (1.25 point). The score of the 31% group was 2.15 point which was significantly lower than the other groups with deeper cutting depth.The roughness score ranged from 2.19 to 3.08 among the 5 group without singnificant difference (P >0.05).Conclusion The femtosecond laser produced more ridges in deeper lamellar cuts and the relative cutting depth of 31% might produce an adequate surface quality for femtosecondlaser-as-sisted lamellar anterior keratoplasty.

Objective To investigate the activation state of and expressions of surface co-stimulatory molecules on peripheral CD4+ T cells from patients with pemphigus and healthy human controls.Methods Ninety patients with pemphigus including 24 patients with first-onset pemphigus,51 with quiescent pemphigus and 15 with recurrent pemphigus,as well as 30 healthy human controls were enrolled in this study.Peripheral blood samples were obtained from these subjects followed by lymphocyte isolation.Flow cytometry was performed to detect the expressions of CD69,intercellular adhesion molecule-1 (ICAM-1),inducible co-stimulatory molecule (ICOS),CD40 ligand (CD40L) and OX40 on CD4+ T cells.Statistical analysis was done by Mann-Whitney test using Graphpad 5.0 software.Results The expression rate of CD69 on peripheral CD4+ T cells from the healthy human controls was significantly lower than that from patients with pemphigus,patients with first-onset pemphigus,patients with quiescent pemphigus,and patients with recurrent pemphigus ((1.26 ± 0.19)％ vs.(2.46 ± 0.19)％,(2.77 ± 0.40)％,(2.15 ± 0.25)％ and (2.36 ± 0.35)％,all P ＜ 0.05).The patients with pemphigus also showed a significant increase in the expression rates of ICAM-1,CD40L and OX40 compared with the healthy human controls ((55.88 ± 1.67)％ vs.(47.75 ± 2.52)％,P＜ 0.05; (2.23 ± 0.22)％ vs.(0.73 ± 0.07)％,P＜ 0.01; (2.55 ± 0.29)％vs.(0.62 ± 0.17)％,P ＜ 0.01).No significant differences were observed between patients with different stages of pemphigus in the expression rates of CD69,ICAM-1,CD40L or OX40 (all P ＞ 0.05).The percentage of ICOS-expressing CD4+ T cells was significantly up-regulated in only patients with first-onset pemphigus as compared to the healthy controls ((3.73 ± 0.60)％ vs.(2.39 ± 0.16)％,P ＜ 0.05).Conclusions The peripheral blood CD4+ T cells from patients with pemphigus are in a relatively active state with up-regulated surface expressions of many costimulatory molecules,suggesting that CD4+ T cells are involved in the initiation and progression of pemphigus by interacting with B cells through co-stimulatory molecules.

Objective To investigate in vivo the protective effects of intraocular injection of ?-crystallin after optic nerve injury.Methods Sixteen rats were divided into normal control group,and 2-week,4-week,6-week groups after optic nerve lesion.?-crystallin and bovine serum albumin(BSA) was respectively injected into the right and left corpus vitreums after the optic nerve crush injury.CTB conjugates were injected into the vitreous of all the rats at 48 h before observing optic nerve with confocal microscope(488 nm).Results It could be seen the normal stripe of the nerve fiber in the injuried optic nerve stained with CTB conjugates and some dots and lumps of fluorescence could be seen in the optic nerve.The fluorescence intensity of the ?-crystallin group was notably higher than the BSA group.Conclusion CTB conjugates anterograde labeling is a reliable and convenient method to observe the optical nerve fiber after optic nerve lesion.?-crystallin administered intraocularly at the lesion time can protect the optic nerve fiber.