Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.

Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.
Azoospermia/genetics* ; Chromosome Aberrations ; Humans ; Infertility, Male/genetics* ; Male ; Oligospermia/genetics* ; Translocation, Genetic

Objective To investigate the application value of the modified Overlap esophagojejunostomy in totally laparoscopic total gastrectomy (TLTG).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 32 patients who underwent TLTG with modified Overlap esophagojejunostomy in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine between January 2015 and December 2017 were collected.The main points of the modified Overlap method:surgeons stood on the right of patients when digestive tract reconstruction,suspension of left half liver and clockwise rotation before esophageal transection were performed,regulating esophageal opening position and building jejunal loop,and then closing openings using 45.0 mm Endo-GIA and barbed wire.Patients who were diagnosed as Ⅰ A stage by postoperative pathological examination were followed up;patients with lymph node metastases underwent chemotherapy of XELOX regimen and patients in Ⅰ B and Ⅱ stages without lymph node metastases underwent oral S-1 single agent.Observation indicators:(1) surgical and postoperative recovery situations;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative adjuvant therapy,long-term complications and survival up to March 2018.Measurement data with normal distribution were represented as x±s,and measurement data with skewed distribution were described as M(range).Results (1) Surgical and postoperative recovery situations:all the 32 patients underwent successful TLTG and modified Overlap esophagojejunostomy.The operation time,esophagojejunostomy time,volume of intraoperative blood loss,time to initial anal exsufflation,time for initial fluid diet intake,time for initial semifluid diet intake and time of postoperative drainage-tube removal were respectively (227 ± 19) minutes,(22 ±7)minutes,(69±11)mL,(2.1±0.5) days,(3.4±0.4) days,(4.9±0.6) days and (7.5±1.7) days.There was no anastomotic stoma-related complication in 32 patients.One patient was complicated with duodenal stump leakage at 5 days postoperatively and was cured by continuous three-cavity irrigation and conservative treatment.Results of postoperative pathological examination:number of lymph node dissected in 32 patients was 32±4.TNM staging:1,5,7,11,6,1 and 1 patients were detected respectively in Ⅰ A,Ⅰ B,Ⅱ A,Ⅱ B,ⅢA,ⅢB and ⅢC.Duration of postoperative hospital stay of 32 patients was (8.1 ±2.1)days.(2) Follow-up and survival situations:32 patients were followed up for 3-38 months,with a median time of 18 months.During the follow-up,in addition to 1 patient in IA stage,31 patients underwent postoperative adjuvant therapy;patients can take the common soft food,without symptoms of choking and burning feelings,and gastroscopy reexamination was performed at 6 months postoperatively and showed anastomosis patency.One patient died of malignant tumor of maxillary sinus at 9 months postoperatively,1 was detected liver metastasis at 20 months postopeartively and survived with tumor,the other patients had no tumor recurrence or metastasis.Conlusion The modified Overlap esophagojejunostomy is safe and feasible in TLTG,with good short-term outcomes.

Super hydrophobic interface modified with silver nanoparticles was fabricated for the detection of pesticide residues.By using a chemical reduction method,silver nanoparticles were deposited on the substrate surfaces with different microscopic pore structures.Two kinds of composite substrates,including regular stainless steel mesh and cellulose polyester film,were used.The pre-treatment of the substrate with fluoridated reagents was used to form a super hydrophobic interface,which made the target molecules on the surface concentrate effectively.The surface with the cellulose polyester substrate was used to detect Rhodamine 6G (R 6G) effectively with surface enhanced Raman scattering (SERS) technique.The results showed that the detection hmit was 10-16 mol/L.In addition,the surfaces based on the stainless steel mesh and cellulose polyester substrate were used to detect trichlorfon pesticide with detection limits of 1 × 10-15 mol/L and 1 × 10-16 mol/L,respectively.

OBJECTIVETo evaluate the clinical significance of low ligation of inferior mesenteric artery (IMA) and preservation of left colic artery in laparoscopic radical operation for rectal cancer.

METHODSClinical data of 103 rectal cancer patients undergoing laparoscopic radical operation in Ruijin Hospital from May 2015 to January 2016 were retrospectively analyzed, including 61 cases with preservation of left colic artery (low ligation group, LL group) and 42 cases without preservation of left colic artery (high ligation group, HL group). Clinical conditions during operation and after operation were compared between the two groups.

RESULTSAll the patients underwent operation successfully without transferring to laparotomy, intra-operative or post-operative death, and severe intra-operative or anesthetic complications. Age, gender, BMI, ASA score, tumor size and tumor location were not significantly different between the two groups. Four cases(9.5%) in HL group presented ischemic changes in colonic stump during operation, receiving additional colonic resection and no such ischemic changes were found in LL group (P=0.025). The number of harvested lymph node was 16.1±6.8 in HL group and 15.5±7.2 in LL group, number of harvest lymph node in the root of IMA was 4.2±1.7 in HL group with positive rate of 9.5%(4/42) and 4.3±1.7 in LL group with positive rate of 4.9%(3/61), both were not significantly different between the two groups. Lower margin was (2.2±1.4) cm in LL group and (2.8±1.7) cm in HL group, and difference was not significant as well(all P>0.05). There were no significant differences in terms of operation time, blood loss, post-operative complication, recovery of bowel movement and hospital stay. Median follow-up time was 4.5 months(2 to 10 months) and no long-term complications and local recurrence were found.

CONCLUSIONLow ligation of IMA with preservation of left colic artery in laparoscopic radical operation for rectal cancer can provide better blood supply for proximal colon and anastomosis, and can achieve same radical clearance of lymph nodes as high ligation without prolonged operation time, which is worth clinical promotion.

Colon ; Female ; Humans ; Laparoscopy ; Length of Stay ; Ligation ; Lymph Node Excision ; Lymph Nodes ; Male ; Mesenteric Artery, Inferior ; Mesenteric Artery, Superior ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Complications ; Rectal Neoplasms ; surgery ; Retrospective Studies