As evidence-based medicine advances and the number of published acupuncture clinical trials in international journals increases,the quality of these trials has become a major focus.The inherent diversity,complexity,and individualization of acupuncture treatments pose unique challenges for quality control in multicenter clinical studies,particularly in Investigator-Initiated Trial(IIT).Refined quality control is essential for the successful conduct of multicenter clinical trials in acupuncture.This study uses the multicenter clinical trials of acupuncture led by our research group as a case study to summarize the quality control experiences throughout the entire process of multicenter IITs.It synthesizes quality control strategies across the trial lifecycle,examines the management of key elements such as participants,materials,data,and specimens,and discusses project design,process management,protocol adherence,and subject safety.These insights are intended to enhance the scientific rigor and reliability of the trials,providing a reference and point of view for researchers in future similar studies.

As evidence-based medicine advances and the number of published acupuncture clinical trials in international journals increases,the quality of these trials has become a major focus.The inherent diversity,complexity,and individualization of acupuncture treatments pose unique challenges for quality control in multicenter clinical studies,particularly in Investigator-Initiated Trial(IIT).Refined quality control is essential for the successful conduct of multicenter clinical trials in acupuncture.This study uses the multicenter clinical trials of acupuncture led by our research group as a case study to summarize the quality control experiences throughout the entire process of multicenter IITs.It synthesizes quality control strategies across the trial lifecycle,examines the management of key elements such as participants,materials,data,and specimens,and discusses project design,process management,protocol adherence,and subject safety.These insights are intended to enhance the scientific rigor and reliability of the trials,providing a reference and point of view for researchers in future similar studies.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.

To achieve better results of the goal of training students' abilities in medical education,formative assessment has been implemented in medical immunology teaching for grade 2014 clinical medicine students.The evaluation indexes of medical immunology teaching have been constructed.Formative assessment has been implemented in classroom teaching,self-learning and group discussion,experimental teaching and network exams by following the principles of feedback,guidance and encouragement.Compared with summative assessment,formative assessment can dynamically reflect the learning progress of immunology and improve the learning effect.The deficiencies andpuzzlesin implementing the formative assessment have also been rethought and discussed deeply.

Aim To investigate the promoting apoptosis effect of artesunate( ART) on human colon cancer Lovo cells and its mechanisms. Methods MTT assay was performed to determine the anti-proliferative effect of artesunate. Flow cytometry assay and electron micros-copy( EM) were used to evaluate the apoptotic effect of artesunate. Luciferase reporter assay was introduced to measure the activation of Wnt/β-catenin pathway. Western blot was used to detect the pathway-related protein levels of β-catenin, GSK-3β,c-Myc and apop-tosis-related protein level of casepase-3 . Results Compared with the control group, the inhibitory rate of cell proliferation at 72 h and 320 μmol·L-1 ART was (78. 99 ± 1. 95 )% ( F =898. 301, P =0. 000 ); the cell apoptotic rate at 24 h and 160 μmol · L-1 ART was(19. 00 ± 0. 05)% and morphological signs of cell apoptosis were found by EM;the transcriptional activi-ty of TCF4/LEF at 24 h and 160 μmol·L-1 ART was (0. 36 ± 0. 30)%(F =470. 954,P <0. 01); the ex-pressions of caspase-3 and GSK-3β were significantly increased, whileβ-catenin and c-Myc were significant-ly decreased when treated with different concentrations of ART for 48 h ( P <0. 01 ) . Conclusion ART may significantly inhibit proliferation and promote apoptosis of Lovo cells probably by inactivating Wnt/β-catenin pathway.

Curcumin can suppress the proliferation of esophageal cancer cells by inducing cell cycle arrest and blocking Notch signaling pathway,and can inhibit the invasiveness of esophageal cancer cells by inhibiting the nuclear factor-κB (NF-κB) signaling pathway and suppressing the formation of tumor blood vessels and inhibiting matrix metalloproteinase (MMP).Curcumin can also regulate apoptosis of esophageal cancer cells by changing the expression and localization of nucleophosmin.

OBJECTIVETo explore the different effects of systolic blood pressure (SBP) and low density lipoprotein on carotid plaques (LDL-C).

METHODSA total of 101 510 serving and retired workers of a company who participated in the health examination in 2006-2009, 5852 participants were selected as study subjects by stratified random sampling according to the age and sex ratio. These subjects took their health examination in 2010-2011 including the carotid ultrasound. Finally, 5361 eligible participants with complete data were included in the analysis. The detection and weighted rates of carotid plaques were calculated for four groups: normal SBP and LDL-C group (3524 subjects), normal SBP and high LDL-C group (356 subjects), elevated SBP and normal LDL-C group (1308 subjects) and elevated SBP and high LDL-C group (173 subjects). The effects of different baseline SBP and LDL-C on detection rates of the carotid artery plaques were analyzed by logistic regression.

RESULTSThe detection rate of carotid plaques in normal SBP and LDL-C group, normal SBP and high LDL-C group, elevated SBP and normal LDL-C group, elevated SBP and high LDL-C group was 33.7% (1186/3524), 41.3% (147/356), 64.8% (847/1308), 68.8% (119/173) (χ(2) = 425.75, P < 0.05) and the weighted detection rate was 36.0%, 42.0%, 64.5% and 68.3% respectively. For men, the detection rate was 44.2% (877/1985), 51.1% (97/190), 70.6% (657/930), 71.3% (82/115) (χ(2) = 194.02, P < 0.05) and the weighted detection rate was 31.2%, 36.1%, 49.8% and 50.3% respectively. For women, the detection rate was 20.1% (309/1539), 30.1% (50/166), 50.3% (190/378), 63.8% (37/58) (χ(2) = 180.17, P < 0.05) and the weighted detection rate was 30.9%, 46.3%, 70.3%, and 88.1% respectively. After adjusted for other risk factors, the OR (95%CI) value was 1.37 (1.05 - 1.78), 2.05 (1.74 - 2.43) and 2.12 (1.45 - 3.12) for normal SBP and high LDL-C group, elevated SBP and normal LDL-C group and elevated SBP and high LDL-C group respectively compared with normal SBP and LDL-C group.

CONCLUSIONElevated SBP and high LDL-C were risk factors of the carotid artery plaques. Compared with high LDL-C, elevated SBP may add a higher risk for carotid plaques.

Adult ; Aged ; Blood Pressure ; Carotid Stenosis ; blood ; epidemiology ; physiopathology ; Cholesterol, LDL ; blood ; Dyslipidemias ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Systole

Objective To study the putative mechanisms underlying fetal alcohol syndrome by comparative protein-profile analysis between normal and ethanol-treated zebrafish embryo with twodimensional electrophoresis (2-DE).Methods Zebrafish embryos were exposed in 400 mmol/L ethanol at dome stage for 3 hours,and then ethanol-induced abnormalities were observed.Proteomes of zebrafish embryos at early stages including zygote stage,dome stage,shield stage and 5-somite stage,were separated by 2-DE.The subtraction analysis method was applied to eliminate the interference from maternal derived proteins.The ethanol-treated embryos at 5-somite stage was analyzed by 2-DE,and the protein profile was compared with that generated from control embryos at the same stage.The data obtained from 2-DE analysis were verified by in-situ hybridization.Results 400 mmol/L ethanol treatment caused axial malformation (62%) and cyclopia (60%) in zebrafish embryos.The 2-DE analysis showed that the expression of Collagen2al (Col2a1) and TAR DNA binding protein (TDP) was decreased in 12 hours post fertilization (12 hpf) ethanol-treated embryos by 81% and 73%,respectively.The in-situ hybridization also demonstrated that the expression of Col2al in axial mesoderm was reduced by ethanol treatment at the same stage.But for 24 hpf ethanoltreated embryos,the expression of Col2al in axis recovered to a comparable level to that in control embryos,while the structure of neural tube was disrupted severely by ethanol exposure.Conclusions It is suggested that the expressions of Col2al and TDP were disrupted by ethanol during early stage,which might induce the zebrafish developmental abnormalities.The ethanol interference on early expression of Col2al is supposed to be one of the major reasons leading to later abnormalities of axis and neutral tube.