Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Objective To analyze the disease burden of early-onset colorectal cancer (EOCRC) at the global, regional, and national levels from 1990 to 2021, and to predict the disease burden trend from 2022 to 2026. Methods Based on the Global Burden of Disease (GBD) database, the incidence, mortality, and disability-adjusted life year (DALY) rate of EOCRC across 204 countries and regions from 1990 to 2021 were obtained. The time trends of these indicators were assessed by calculating the estimated annual percentage change (EAPC), and the contributions of ten risk factors to the EOCRC burden were analyzed. The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden from 2022 to 2026. Results From 1990 to 2021, the number of new global EOCRC cases increased from 107 310 to 211 890, with the incidence rising from 3.96 to 5.37 per 100 000 people. In 2021, global EOCRC incidence, mortality, and DALY rate increased with age; males had higher rates than females in terms of incidence, mortality, and DALY rate in all age groups. In 2021, East Asia had the highest number of new cases, deaths, and DALY. From 1990 to 2021, the global EAPC for incidence rate was 0.96%, and death rate was –0.38%. ARIMA model indicated that from 2022 to 2026, the global incidence of EOCRC would continue to rise, while mortality and DALY rate would be expected to decline. Conclusions The disease burden of EOCRC has significantly increased globally from 1990 to 2021, with notable regional, age, and sex differences. By 2026, the mortality and DALY rate of EOCRC will decline, while the incidence is expected to further increase, highlighting the urgency of taking active measures to address the growing trend of EOCRC.

Objective To compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Objective To explore the feasibility and clinical value of endoscopic resection of duodenal papilla tumors with a maximum diameter greater than 3 cm. Methods A retrospective analysis was conducted on the clinical data of all 12 patients who underwent endoscopic resection of duodenal papilla tumors at the Endoscopy Center of Zhongshan Hospital (Xuhui Hospital), Fudan University and Rongcheng Hospital of Traditional Chinese Medicine from September 2017 to May 2023. The size of the tumors all exceeded 3 cm. Results All 12 patients successfully completed the operation, with a complete resection rate of 91.7% (11/12) and an en-bloc resection rate of 91.7% (11/12). One patient experienced delayed bleeding due to unclosed wound during operation and received endoscopic hemostasis; 11 cases underwent partial wound closure operation with pancreatic and biliary stent placement, without perforation or postoperative stenosis. Among them, 2 cases (18.2%) experienced delayed bleeding and received endoscopic hemostasis treatment. After operation, 1 case (8.3%) experienced nausea, vomiting, upper abdominal discomfort, and elevated blood amylase levels, who was later treated conservatively. During the mean follow-up period of 30.5 (1.0-69.0) months, 1 patient experienced recurrence and underwent surgical resection. Conclusions Endoscopic resection of duodenal papilla tumors can treat large diameter duodenal papilla tumors exceeding 3 cm, but postoperative complications may occur and require special attention. Postoperative placement of pancreatic and biliary stents and wound closure may reduce the incidence of complications.

To investigate the evaluation and management of gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, a retrospective analysis was performed on 15 patients with gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, who were treated at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2012 to October 2022. All patients were treated successfully after comprehensive treatment. Three patients received metal clipping and gastric tube drainage; 10 patients received gastric tube drainage combined with jejunal nutritional tube placement, and 7 of them had gastric tube directly put into the fistula cavity; 2 patients received covered esophageal stent placement combined with jejunal nutritional tube placement. Five patients received wound tissue glue spraying; 2 patients underwent purse-string suture with nylon loops and metal clips after reduced fistula burned by hot biopsy forcep or argon plasma coagulation. The gastrointestinal fistula after tunnel endoscopic surgery is a complex postoperative complication, which needs early detection, careful evaluation and comprehensive treatment.

To investigate the feasibility and safety of endoscopic trans-gastric cholecystolithotomy(ETGC) combined with endoscopic retrograde cholangiopancreatography (ERCP) for cholecystolithiasis and choledocholithiasis. Data of patients with cholecystolithiasis and choledocholithiasis who underwent ETGC after ERCP in Zhongshan Hospital Affiliated to Fudan University from November 2018 to April 2019 were analyzed. Six patients with cholecystolithiasis and choledocholithiasis, 4 males and 2 females, were included in this study.The interval between ERCP and ETGC ranged from 1 to 77 days (median 5 days). All the 6 patients successfully completed ETGC after ERCP, with a surgical success rate of 100%. All the patients had multiple cholecystolithiasis and one patient was complicated with gallbladder polyps.The ETGC operation time was 22-100 min (median 65 min), and the length of hospital stay was 3-9 d (median 6.5 d). Two patients had dull pain in the upper abdomen and increased body temperature after surgery. Abdominal ultrasound in one patient suggested local effusion in the right upper abdomen.Both patients improved after conservative treatment.None of the patients had cholecystitis and cholangitis related symptoms such as right upper abdominal pain or fever during postoperative follow-up, and the follow-up rate was 100%with median follow-up time of 18 month.All the 6 patients underwent abdominal ultrasound examination after surgery. No recurrence occurred in 5 patients. One of the patients showed cholesterol crystals in the gallbladder wall and bile mud deposition.ETGC combined with ERCP is safe and feasible for cholecystolithiasis and choledocholithiasis.

Objective: To evaluate the feasibility and short-term efficacy of a novel and simplified closure method developed by our team for the defect closure after endoscopic full-thickness resection (EFTR) for gastric submucosal tumors (SMT) in the gastric wall. Methods: A prospective single-arm clinical study was used. Inclusion criteria: (1) the lesion was located in the fundus or the greater curvature of the stomach, and was confirmed to originate from the muscularis propria layer; (2) the diameter of the tumor was ≤3.5 cm, and the tumor had no extensive adhesion to the peritoneal tissues and organs in extraperitoneal cavity; (3) the tumor had no malignant features under ultrasound endoscopy; (4) the patient agreed to participate in the study; (5) patients with severe complications were excluded. Based on the above criteria, 20 patients with gastric SMT at the Endoscopy Center of Zhongshan Hospital of Fudan University from January 2015 to March 2018 were enrolled in this study, including 5 males and 15 females with mean age of 61.1 (38 to 70) years. Grasping forceps-assisted endo-loop snare ligation device which is called "Shao-Mai" method was used to close the defect site. All the patients underwent EFTR and "Shao-Mai" method to perform defect closure. After successful tumor resection by EFTR, an endo-loop was anchored onto the edge of the gastric defect with grasping forceps assistance and closed tightly. The observation indicators included tumor size, en bloc resection, operation time, postoperative complications and hospital stay. The follow-up indicators included tumor residual, local recurrence, and metachronous lesions. Results: All the 20 lesions were located in the muscularis propria with a size of 0.5-3.5 (mean 1.4) cm. Three of them were located in the greater curvature of the mid-upper gastric body, 17 were located in the fundus. The endoscopic "Shao-Mai" closure was successfully performed after EFTR in all the 20 cases. Endoscope was used uniquely through the entire process, without laparoscopic assistance. The operative time was 20-100 (mean 43.8) minutes, while the "Shao-Mai" closure procedure took a range of 3-30 (mean 10.1) minutes. The en bloc resection rate was 100%. The pathological diagnosis included 17 gastrointestinal stromal tumors and 3 leiomyomas. No major complications occurred during or after surgery. All the patients were discharged 1-11 (mean 3.1) days after operation. The wounds of all the cases were healed completely six months after operation and only scar was observed without ulcer. No residual lesion, tumor recurrence or metastasis, leakage or fistula of digestive tract were found during the follow-up period of 15-54 (median 41) months. Conclusion The endoscopic "Shao-Mai" closure method is a simplified novel way, which is feasible, effective, and safe for closing the gastric defect after EFTR.

Objective To evaluate the safety and efficacy of dental floss traction?assisted endoscopic submucosal dissection (DFS?ESD) for rectal neuroendocrine neoplasm (NEN). Methods A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital ,Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled,including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1,and the mean size was 0.8±0.2(0.5?1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS?ESD treatment (DFS?ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS?ESD group,after the mucosa was partly incised along the marker dots ,the endoscopy was extracted,and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted,the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time,modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS?ESD group),en bloc resection rate,R0 resection rate, morbidity of operative complication,recurrence and metastasis were compared between two groups. Results The average tumor size was (0.8±0.2) cm in DFS?ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425,P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm,13 were G1 and 4 were G2 in DFS?ESD group,while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative,the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS?ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS?ESD group (t=1.776,P=0.084). The modified operation time of DFS?ESD group was (11.9±2.8) minutes,which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3 ± 0.6) days and (2.0 ± 0.5) days in conventional ESD group and DFS?ESD group,respectively,without significant difference (t=1.436,P=0.160). No patient was transferred to surgery,and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor?related death,and all the patients recovered well during a follow?up period of 14(1?24) months. Conclusion Dental floss traction?assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Objective To evaluate the clinical value of dual channel dual curved endoscope in the endoscopic submucosal dissection (ESD) for gastric angle mucosal lesions. Methods A descriptive cohort study was carried out. Clinicopathological data of 20 cases with gastric angle mucosal lesions undergoing ESD by dual channel dual curved endoscope in our center from October 2016 to August 2018 were collected and analyzed retrospectively. Inclusion criteria: (1) the lesion was located in the gastric angle confirmed by gastroscopy before ESD. (2) CT examination showed no distant metastasis. (3) pathological biopsy confirmed precancerous lesion or early cancerous lesion without submucosal invasion. (4) the whole operation was performed by the same endoscopist with ESD experience of about 2000 cases. Patients with previous ESD history of gastric angle and other serious diseases were excluded. The dual channel dual curved endoscopy (Olympus, GIF?2TQ260M) and other conventional endoscopic surgical instruments were used in all the cases. Complete tumor resection rate, pathological results, intraoperative and postoperative complications, operation time and hospitalization time were observed. Follow?up parameters included residual tumor, local recurrence and heterogeneous lesion. Results Of 20 patients, 14 were male and 6 were female with an average of 55.6 years (range, 37 to 75). All the tumors located in gastric angle. Specimen size ranged from 1.2 to 5.5 (average 2.9) cm. Operation time ranged from 50 to 120 (average 85.8) minutes. Hospital stay ranged from 3 to 7 (average 5.1) days. The en bloc excision was performed successfully in all 20 cases. There was no perforation or bleeding during or after operation. Pathological results showed curative or nearly curative resection stage in all the cases. No tumor residual or recurrence was found during follow?up for 8 to 30 (average 18.5) months. Conclusion Dual channel dual curved endoscope can provide good vision and easy control in removing the lesion completely and avoiding complications during the ESD procedure in gastric angle mucosal lesions with good long?term efficacy.

Objective To evaluate the safety and efficacy of dental floss traction?assisted endoscopic submucosal dissection (DFS?ESD) for rectal neuroendocrine neoplasm (NEN). Methods A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital ,Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled,including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1,and the mean size was 0.8±0.2(0.5?1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS?ESD treatment (DFS?ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS?ESD group,after the mucosa was partly incised along the marker dots ,the endoscopy was extracted,and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted,the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time,modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS?ESD group),en bloc resection rate,R0 resection rate, morbidity of operative complication,recurrence and metastasis were compared between two groups. Results The average tumor size was (0.8±0.2) cm in DFS?ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425,P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm,13 were G1 and 4 were G2 in DFS?ESD group,while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative,the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS?ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS?ESD group (t=1.776,P=0.084). The modified operation time of DFS?ESD group was (11.9±2.8) minutes,which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3 ± 0.6) days and (2.0 ± 0.5) days in conventional ESD group and DFS?ESD group,respectively,without significant difference (t=1.436,P=0.160). No patient was transferred to surgery,and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor?related death,and all the patients recovered well during a follow?up period of 14(1?24) months. Conclusion Dental floss traction?assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.