Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of 45 patients with active CD at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2020 to May 2022 were analyzed. All of the patients received VDZ at the dose of 300 mg per time at 0, 2th, 6th weeks and subsequently once every 8 weeks. The clinical response and remission were evaluated by Crohn′s disease activity index (CDAI) . The endoscopic response and remission were evaluated by simple endoscopic score for Crohn′s disease (SES-CD) . All of the adverse effects occurred during the treatment of VDZ were recorded in order to evaluate the safety. The primary endpoint was the clinical remission rate at 22 weeks after treatment. The secondary endpoints included the clinical response rate at 22 weeks after treatment, the clinical response rate and clinical remission rate at 52 weeks after treatment, the endoscopic response rate and remission rate at (22 ± 8) weeks after treatment. Thirty-one patients who had previously used infliximab (IFX) and adalimumab (ADA) were set as non-Bio-Na?ve group, and 14 patients who had not previously used biologics were set as Bio-Na?ve group. The differences of the primary endpoint and some secondary endpoints between the two groups were compared.Results:At 22 weeks after treatment, the CDAI score of 45 patients decreased from baseline (261.4 ± 98.3) points to (166.6 ± 93.5) points, the difference was statistically significant ( t = 4.6, P<0.01) . Among them, 64.4% (29/45) patients achieved clinical response and 46.7% (21/45) patients achieved clinical remission. There were no significant difference in clinical response rate [71.4% (10/14) vs. 61.3% (19/31) , χ 2 = 0.4, P = 0.4] and clinical remission rate [42.9% (6/14) vs. 48.4% (15/31) , χ 2 = 0.1, P = 0.8] between the Bio-Na?ve group and non-Bio-Na?ve group at 22 weeks after treatment. At 52 weeks after treatment, the CDAI score of 33 patients decreased from baseline (306.9 ± 130.7) points to (126.6 ± 92.7) points, the difference was statistically significant ( t = 8.5, P<0.01) . Among them, 39.4% (13/33) of the patients achieved clinical response, 33.3% (11/33) of the patients achieved clinical remission, but 41.4% (12/29) of the patients had secondary loss of response. At (22 ± 8) weeks after treatment, the SES-CD score of 25 patients in active phase under endoscopy at baseline decreased from baseline 13.0 (7.0, 19.0) points to 8.0 (2.5, 18.5) points, the difference was statistically significant ( Z = -2.6, P<0.05) . Among them, 40.0% (10/25) patients achieved endoscopic response and 20.0% (5/25) patients achieved endoscopic remission. The new facial rash occurred in 1 patient (2.2%) , new joint pain in 2 (4.4%) and there was no new active tuberculosis and hepatitis B virus infection during the treatment of VDZ for 45 patients. Conclusions:Single drug of VDZ has a good effect on inducing remission in patients with mild to moderate CD and has a good safety. The previous use of IFX or ADA does not affect the efficacy of VDZ, but part of patients still have secondary loss of response.

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of 45 patients with active CD at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2020 to May 2022 were analyzed. All of the patients received VDZ at the dose of 300 mg per time at 0, 2th, 6th weeks and subsequently once every 8 weeks. The clinical response and remission were evaluated by Crohn′s disease activity index (CDAI) . The endoscopic response and remission were evaluated by simple endoscopic score for Crohn′s disease (SES-CD) . All of the adverse effects occurred during the treatment of VDZ were recorded in order to evaluate the safety. The primary endpoint was the clinical remission rate at 22 weeks after treatment. The secondary endpoints included the clinical response rate at 22 weeks after treatment, the clinical response rate and clinical remission rate at 52 weeks after treatment, the endoscopic response rate and remission rate at (22 ± 8) weeks after treatment. Thirty-one patients who had previously used infliximab (IFX) and adalimumab (ADA) were set as non-Bio-Na?ve group, and 14 patients who had not previously used biologics were set as Bio-Na?ve group. The differences of the primary endpoint and some secondary endpoints between the two groups were compared.Results:At 22 weeks after treatment, the CDAI score of 45 patients decreased from baseline (261.4 ± 98.3) points to (166.6 ± 93.5) points, the difference was statistically significant ( t = 4.6, P<0.01) . Among them, 64.4% (29/45) patients achieved clinical response and 46.7% (21/45) patients achieved clinical remission. There were no significant difference in clinical response rate [71.4% (10/14) vs. 61.3% (19/31) , χ 2 = 0.4, P = 0.4] and clinical remission rate [42.9% (6/14) vs. 48.4% (15/31) , χ 2 = 0.1, P = 0.8] between the Bio-Na?ve group and non-Bio-Na?ve group at 22 weeks after treatment. At 52 weeks after treatment, the CDAI score of 33 patients decreased from baseline (306.9 ± 130.7) points to (126.6 ± 92.7) points, the difference was statistically significant ( t = 8.5, P<0.01) . Among them, 39.4% (13/33) of the patients achieved clinical response, 33.3% (11/33) of the patients achieved clinical remission, but 41.4% (12/29) of the patients had secondary loss of response. At (22 ± 8) weeks after treatment, the SES-CD score of 25 patients in active phase under endoscopy at baseline decreased from baseline 13.0 (7.0, 19.0) points to 8.0 (2.5, 18.5) points, the difference was statistically significant ( Z = -2.6, P<0.05) . Among them, 40.0% (10/25) patients achieved endoscopic response and 20.0% (5/25) patients achieved endoscopic remission. The new facial rash occurred in 1 patient (2.2%) , new joint pain in 2 (4.4%) and there was no new active tuberculosis and hepatitis B virus infection during the treatment of VDZ for 45 patients. Conclusions:Single drug of VDZ has a good effect on inducing remission in patients with mild to moderate CD and has a good safety. The previous use of IFX or ADA does not affect the efficacy of VDZ, but part of patients still have secondary loss of response.

[Abstract] Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1（TGIF1）axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24, 5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_ 0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assayconfirmedthatthereisatargetingrelationshipbetweencirc_0001429andmiR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.

Ojbective To predicte the HLAⅠrestricted CTL epitopes and B cell antigen epitopes derived from tumor antigen SCCAg. Methods The linear B cell epitopes and conformational B cell epitopes of tumor antigen SCCAg were predicted by Ellipro program. In addition, the HLAⅠrestricted CTL epitopes of SCCAg were predicted by NetCTL, Prot-Param and so on. Results B cell epitopes analysis revealed that SCCAg had 10 potential linear B cell epitopes and 5 conformational B cell epitopes; Combined with peptide HLAⅠbinding, proteasomal C - terminal cleavage and TAP transport efficiency, the NetCTL predicts that multiple HLAⅠrestricted CTL epitopes were present in the tumor antigen SCCAg. Conclusion The B cell epitopes and HLAⅠrestricted CTL epitopes can be predicted by multiple methods, which may lay the foundation for the further research on immunotherapy for targeting SCCAg.

Objective To investigate the effect of knockdown or overexpression of G6PD on proliferation, growth and migration of human hepatocellular carcinoma cell PLC/PRF/5. Methods Lentivirus-mediated knock-down or overexpression of G6PD was achieved in human hepatocellular carcinoma cell line PLC/PRF/5. RT-PCR and Western blotting assay were used to detect the overexpression or knockdown of G6PD.Cell proliferation and mi-gration curves were recorded by real-time cell analysis system(RTCA),the cell proportion in the DNA replication phase can be directly displayed with EDU experiment,cell growth ability was detected by colony forming assay. Results The doubling time of cells in G6PD knockdown group was longer than that of the control group,and the cell growth rate decreased significantly,the proportion of cells in proliferative phase(43.2%)was lower than that in the control group,but the rates colony formation and migration were significantly decreased(P<0.05,respective-ly),and the migration curves separated apparently.While no significant differences in proliferation,growth and mi-gration of PLC/PRF/5 cells were found between the over-expressed strain and the control group. Conclusion The reduction of G6PD expression in HCC cells inhibits the proliferation and growth of HCC,which may lay a foun-dation for the further study of the pathogenesis and treatment of HCC.

Background Sclera remodeling process in axial elongation is one of the main pathological mechanisms of axial myopia progression.Studies confirmed that transforming growth factor-β1(TGF-β1) participates in the sclera remodeling process,and Smad3 is one of TGF-β1 downstream signal gene transcriptive factors,so to explore its role in sclera remodeling process of myopic eyes is of great significance for pathogenesis and prevention research of myopia.Objective This study was to investigate the expressions of type Ⅰ collagen and Smad3,a TGF-31 downstream target,in sclera of form deprivation myopic (FDM) eyes and explore the impact of TGF-β1-Smad3-type Ⅰ collagen signaling pathway on collagen remodeling in myopic sclera.Methods Seventy-five 1-week-old guinea pigs were randomly divided into normal control group (25 guinea pigs) and FDM group (50 guinea pigs).Monocular FDM was induced by occluding the left eyes of guinea pigs in FDM group with translucent latex balloons for 2,4,6 weeks,respectively,and consecutive occluding for 4 weeks followed by uncovering for 1 week (4/-1 weeks).The refractive power was detected by retinoscopy and axial length was measured with A-type ultrasound.Immunohistochemistry and reverse transcription-PCR were employed to detect the dynamic expressions of type Ⅰ collagen and Smad3 protein ad mRNA in the sclera of guinea pigs with emmetropia and experimental myopia,ard the relationship between collagen Ⅰ and Smad3 levels was analyzed.Results The refraction was hypermetropic in both normal control group and FDM group before occluding of eyes (P＞0.05),and the hypermetropic power was gradually reduced over time in the normal control group.In the FDM group,the refractive power was gradually changed from (+2.09 ± 0.31)D before occluding to (-1.23±0.69),(-4.17±0.59),(-7.07±0.56) and (-4.30±0.58)D,and the axial length was increased from (5.93-±0.39)mm to (6.62±0.36),(7.30±0.34),(7.99--0.32),and (7.21 ±0.36) mm at weeks 2,4,6,and 4/-1 after occluding,respectively,indicating significant differences in refractive power and axial length over time in the FDM group from normal control group and self-control group (all at P＜0.05).The expressions of Smad3 and type Ⅰ collagen protein and mRNA in the sclera of the FDM group was significantly lower than those of the control group and self-control group in various time points (all at P＜0.05).The positive correlation were found in the expression of Smad3 on the myopic sclera with that of type Ⅰ collagen in both protein and mRNA levels (protein:r=0.993,P＜0.05;mRNA:r=0.954,P＜0.05).Conclusions The myopic power and ocular axis increase dependent upon occluding time,and the expressions of Smad3 and type Ⅰ collagen in the sclera are correspondingly weakened in FDM eyes.A consistent expression trend is found between Smad3 and type Ⅰ collage,suggesting Smad3 and type Ⅰ collagen participate in the regulation of sclera remodeling in myopia by TGF-β1-Smad3-Collagen Ⅰ signaling pathway.

Objective To identify the role of phosphatidylinositol-3-kinase(PI3K) in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) and the involved mechanism.Methods Knockdown of p110α,receptor-interacting protein 1(RIP1) or both p110αand RIP1 was mediated by the specific short hairpin RNA (shRNA) lentivirus and verified by RT-PCR or Western blotting .In addition , Western blotting was used to detect phosphorylation of mixed lineage kinase domain-like protein(MLKL) and protein kinase B(AKT) or tetramerization of MLKL.Cell death was measured by micros-copy and flow cytometry.Results AKT phosphorylation and TNFα-induced necroptosis of L929 cells were suppressed by the inhibitors of PI3K or AKT, as well as p110αknockdown.Moreover, RIP1 knockdown did not inhibit L929 cell death induced by TNFαplus Z-VAD, but the RIP1-independent necroptosis was inhibited by p 110αknockdown.In addition, p110αknockdown suppressed MLKL phosphorylation and tetramerization induced by TNFαwith Z-VAD in L929 cells. Conclusion PI3K mediates necroptosis of L929 cells induced by TNFαby activating AKT and MLKL, respectively.

AIM:To analyze the correlation between serum angiotensin-converting enzyme 2 (ACE2) levels and different stages of coronary heart disease (CHD), and to explore the change of serum ACE2 level during the development of CHD.METHODS:The control group included 85 non-CHD samples, and 174 CHD samples were divided into light stenosis (ls-CHD, stenosis degree <50%) group, moderate stenosis (ms-CHD, stenosis degree 50%~75%) group and severe stenosis (ss-CHD, stenosis degree ≥75%) group.The ACE2 level in each serum sample was detected by ELISA.The relationship between the ACE2 level and the development of coronary heart disease was explored by statistical analysis of serum ACE2 levels in different stages of CHD.RESULTS:The serum ACE2 levels in ls-CHD group, ms-CHD group and ss-CHD group were all higher than that in control group.The more severe the coronary artery stenosis existed, the higher the ACE2 level was observed.The serum ACE2 level in the males was higher than that in the females.In a single sex, the serum ACE2 levels in ls-CHD group, ms-CHD group and ss-CHD group were higher than that in control group with significant differences.Regression analysis found that sex, diabetes and CHD were associated with the serum ACE2 levels.Among them, sex and CHD were the independent factors to affect serum ACE2 levels.CONCLUSION:The serum ACE2 level of males was higher than that of females.Compared with the non-CHD samples, the serum ACE2 level of CHD patients was higher than that of the non-CHD samples.During the development of coronary heart disease, the serum ACE2 level increased constantly.