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 investigate the effects of brusatol on the malignant biological behavior of ovarian cancer cells by regulating the sphingosine kinase 1 （SPHK1）/sphingosine-1-phosphate （S1P）/sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway. METHODS Human ovarian cancer cell strain SKOV-3 were randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， brusatol+SPHK1 overexpression group. The cell viability， colony formation rate， the number of migration and invasion， apoptosis rate， the expressions of cell proliferation-related proteins [myelocytomatosis viral oncogene homolog （C-myc）]， apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）]， epithelial mesenchymal transition （EMT）-related proteins （E-cadherin， N-cadherin） and SPHK1， S1P， S1PR3 proteins were all detected in each group. Transplanted tumor model of nude mice was constructed by using SKOV-3 cells and randomly separated into control group， brusatol low-dose， medium-dose and high-dose groups， SPHK1 overexpression group， high- dose brusatol+blank load group， and high-dose brusatol+SPHK1 overexpression group； the growth of transplanted tumors were detected. The nude mice model of SKOV-3 transplantation tumor was randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， and brusatol+SPHK1 overexpression group； the proliferation and apoptosis of transplanted tumor tissue， the expressions of EMT-related Δ 基金项目江西省中医药管理局科技计划项目（No.2023B0762） ＊第一作者 副主任药师 。研究方向 ：药学研究及药理学 。E- proteins and SPHK1/S1P/S1PR3 signaling pathway proteins mail：jsgj2023@126.com were detected in each group. RESULTS Cell experiments in # 通信作者 主任医师，硕士。研究方向：妇科及妇科肿瘤学。E- vitro had shown that compared with the control group， the cell mail：11638199@qq.com viability， clone formation rate， migration number， invasion 中国药房 2024年第35卷第16期 China Pharmacy 2024 Vol. 35 No. 16 · 1991 · number， protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 were decreased significantly in brusatol group （P＜0.05）， while the apoptosis rate， protein expressions of Bax and E-cadherin were increased significantly （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in SKOV-3 cells. Mice experiments in vivo had shown that compared with the control group， the transplanted tumor volumes of nude mice in the brusatol low-dose， medium- dose and high-dose groups were decreased significantly in a dose-dependent manner after 21 days of intervention （P＜0.05）. Brusatol of high dose could also significantly reduce the protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 in transplanted tumor tissue of nude mice （P＜0.05）， and significantly increase the protein expressions of Bax and E- cadherin （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in transplanted tumor tissue of nude mice. CONCLUSIONS Brusatol can inhibit the proliferation， cloning， EMT， migration and invasion of ovarian cancer cells， and induce their apoptosis by down-regulating the expression of SPHK1/S1P/S1PR3 signaling pathway. It can also inhibit the growth of ovarian cancer cells in nude mice， ultimately suppressing their malignant biological behavior and exerting significant anti-cancer effects on ovarian cancer.

Objective To explore the role of ATM/hnRNPK signaling in the adriamycin resistance of acute myeloid leukemia.Methods Expression of ATM was examined in the adriamycin resistant and sensitive leukemia cell strains with Western blot.ATM expression was down-regulated by RNAi and ATM inhibitor in the adriamycin resist-ant cell strains.Expression level of hnRNPK and LC3Ⅰ/Ⅱ was detected by Western blot and adriamycin sensitivity was measured by CCK8 assay before and after modulation of ATM expression.Results ATM was overex-pressed in adriamycin resistant leukemia cell strains.The decreased expression of ATM restored the sensitivity to adriamycin.Expression level of LC3Ⅱ and hnRNPK was consistent with the modulation of ATM expression.Conclusions The ATM/hnRNPK signaling pathway may play a role in the occurrence of adriamycin resistance in acute myeloid leukemia by regulating autophagy.

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 explore the necessity and safety of selective endoscopy to detect gastrointestinal (GI) malignancy during the outbreak of coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was carried out to analyze the clinical data of selective endoscopy performed at the Endoscopic Center, Zhongshan Hospital of Fudan University from February 20 to March 6, 2020. Clinical data included epidemiological questionnaire, chief complaints, endoscopic findings and biopsy pathology results, etc. All medical staff had blood test for IgM/IgG antibodies of COVID-19. Patients and their families were followed up by phone to determine whether they were infected with COVID-19. Meanwhile, the clinical data of selective endoscopy during the same period from February 20 to March 6, 2019 were collected as the control group to compare the overall results of endoscopy examinations during the epidemic and the detection rate of GI malignancy.Results:A total of 911 patients underwent endoscopy in the epidemic period group, and a total of 5746 cases in the control group, which was 6.3 times over the epidemic period group. In the epidemic period group, 544 cases received gastroscopy and 367 cases received colonoscopy, while 3433 cases received gastroscopy and 2313 cases received colonoscopy in the control group, which were both 6.3 times of epidemic period group. Gastroscopy revealed that 39 patients (7.2%) were diagnosed with upper GI malignancies in the epidemic period group and 77 patients (2.2%) in the control group with significant difference (χ 2=40.243, P<0.001). The detection rate of gastric cancer in these two groups was 3.3% ( n=18) and 1.7% ( n=59) respectively with significant difference (χ 2=6.254, P=0.012). The detection rate of esophageal cancer was 3.7% ( n=20) and 0.5% ( n=18) respectively with significant difference (χ 2=49.303, P<0.001). Colonoscopy revealed that colorectal cancer was found in 32 cases (8.7%) of the epidemic period group and 88 cases (3.8%) of the control group with significant difference (χ 2=17.888, P<0.001). During the epidemic period, no infection of medical staff was found through the blood test of IgM/IgG antibodies on COVID-19. No patient and family members were infected with COVID-19 by phone follow-up. Conclusion:Compared with the same period in 2019, the number of selective endoscopy decreases sharply during the epidemic period, while the detection rate of various GI malignant tumors increases significantly, which indicates that patients with high-risk symptoms of GI malignancies should still receive endoscopy as soon as possible. Provided strict adherence to the epidemic prevention standards formulated by the state and professional societies, it is necessary to carry out clinical diagnosis and treatment as soon as possible.

Objective:To explore the necessity and safety of selective endoscopy to detect gastrointestinal (GI) malignancy during the outbreak of coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was carried out to analyze the clinical data of selective endoscopy performed at the Endoscopic Center, Zhongshan Hospital of Fudan University from February 20 to March 6, 2020. Clinical data included epidemiological questionnaire, chief complaints, endoscopic findings and biopsy pathology results, etc. All medical staff had blood test for IgM/IgG antibodies of COVID-19. Patients and their families were followed up by phone to determine whether they were infected with COVID-19. Meanwhile, the clinical data of selective endoscopy during the same period from February 20 to March 6, 2019 were collected as the control group to compare the overall results of endoscopy examinations during the epidemic and the detection rate of GI malignancy.Results:A total of 911 patients underwent endoscopy in the epidemic period group, and a total of 5746 cases in the control group, which was 6.3 times over the epidemic period group. In the epidemic period group, 544 cases received gastroscopy and 367 cases received colonoscopy, while 3433 cases received gastroscopy and 2313 cases received colonoscopy in the control group, which were both 6.3 times of epidemic period group. Gastroscopy revealed that 39 patients (7.2%) were diagnosed with upper GI malignancies in the epidemic period group and 77 patients (2.2%) in the control group with significant difference (χ 2=40.243, P<0.001). The detection rate of gastric cancer in these two groups was 3.3% ( n=18) and 1.7% ( n=59) respectively with significant difference (χ 2=6.254, P=0.012). The detection rate of esophageal cancer was 3.7% ( n=20) and 0.5% ( n=18) respectively with significant difference (χ 2=49.303, P<0.001). Colonoscopy revealed that colorectal cancer was found in 32 cases (8.7%) of the epidemic period group and 88 cases (3.8%) of the control group with significant difference (χ 2=17.888, P<0.001). During the epidemic period, no infection of medical staff was found through the blood test of IgM/IgG antibodies on COVID-19. No patient and family members were infected with COVID-19 by phone follow-up. Conclusion:Compared with the same period in 2019, the number of selective endoscopy decreases sharply during the epidemic period, while the detection rate of various GI malignant tumors increases significantly, which indicates that patients with high-risk symptoms of GI malignancies should still receive endoscopy as soon as possible. Provided strict adherence to the epidemic prevention standards formulated by the state and professional societies, it is necessary to carry out clinical diagnosis and treatment as soon as possible.

Objective: To investigate the feasibility and safety of endoscopic trans-gastric gallbladder-preserving cholecystolithotomy (ETGC) for gallstones. Methods: The clinical data of 84 cholecystolithiasis patients, who received ETGC at Endoscopic Center of Zhongshan Hospital from March 2017 to May 2019 were analyzed retrospectively. The operation completion rate, operation time, complications and recurrence of calculus were summarized. Results: In the 84 cases of cholecystolithiasis, there were 19 cases (22.6%) of single stone, 53 cases (63.1%) of multiple stones, and 12 cases (14.3%) of gallstones with gallbladder polyps. A total of 82 patients (97.6%) successfully completed ETGC with median operation time of 88 min. Ten patients (12.2%) suffered from abdominal pain after operation, of which 6 patients relieved after conservative treatments. The other 4 cases, including 2 cases of hemoperitoneum, 1 case of biliary fistula, and 1 case of choledocholithiasis with obstructive jaundice, were recovered after corresponding interventions. As of June 14, 2019, 5 cases were lost to follow-up (follow-up rate was 93.9%, 77/82). Residual stones were found in 2 cases (2.6%, 2/77). Stone recurrence was discovered in 4 cases (5.2%, 4/7), and 2 cases (2.6%, 2/77) had cholesterol crystallization in gallbladder. Conclusion ETGC is minimally invasive, feasible and safe in treatment of cholecystolithiasis, and can retain the function of gallbladder. However, how to completely remove the stones and avoid residue by ETGC still needs further exploration, and its long-term efficacy still needs further observation.

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.