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.

Objective To explore the potential mechanism of artemisinin in the treatment of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking technology. Methods The corresponding targets of natural product artemisinin were obtained from PubChem, Swiss Target Prediction and PharmMapper databases, targets related to PCOS were obtained through GeneCards and DisGeNET databases; the intersection target genes of Artemisinin and PCOS were screened by Draw Venn diagram. Then the protein-protein interaction network (PPI) was constructed according to the intersection target genes through the STRING Database, and the core targets were screened by Cytoscape. Besides, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was performed by DAVID Database, and finally the data were analyzed visually by the online platform. Molecular docking of artemisinin and core targets were performed by Chemdraw, Pymol, Auto Dock Tools and RCSB PDB database. Results A total of 229 targets of artemisinin and 1292 targets of PCOS were screened out, 90 overlapping targets were obtained by Draw Venn diagram, and 5 potential core targets, AKT1, ESR1, MMP9, PPARG, MMP2, were mainly act on PI3K Akt, MAPK, RAS, endocrine resistance and other signal pathways. Molecular docking results showed that there were molecular binding sites between artemisinin and core targets. Conclusion It is preliminarily analyzed that artemisinin may play a therapeutic role in PCOS through multiple targets and mechanisms.

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate. Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold. Results The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compound 6f showed attractive anti-C. difficile activity. Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development.

Objective:To analyze the influencing factors related to false-negative results of interferon-γ release assay (IGRA) QFT-GIT in patients with confirmed pulmonary tuberculosis.Methods:Clinical data of 389 patients with bacteriologically confirmed pulmonary tuberculosis who underwent QFT-GIT in Quzhou Hospital Affiliated to Wenzhou Medical University between January 1 and December 31 2020 were retrospectively analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors related to the false-negative results of QFT-GIT.Results:Among 389 confirmed patients, 347 cases had positive QFT-GIT results and 42 cases had negative results. Univariate analysis showed that the false-negative results of QFT-GIT were associated with low BMI, reduced CD4 + T lymphocyte count, decreased lymphocyte count, increased C-reactive protein, negative sputum smear, anemia, diabetes mellitus, malignant tumor and sepsis ( P<0.05 or P<0.01). Multivariate conditional logistic regression analysis showed that BMI <18.5 kg/m 2( OR=1.585, 95% CI 1.076-2.336), complicated with diabetes( OR=5.157, 95% CI 2.340-11.365), malignant tumors ( OR=5.596, 95% CI 2.048-15.295)and sepsis ( OR=4.141, 95% CI 1.042-16.459) were independent risk factors for the false-negative results of QFT-GIT ( P<0.05 or P<0.01). Conclusion:When the pulmonary tuberculosis patients are extreme emaciation, complicated with diabetes, malignant tumor or sepsis, the QFT-GIT results will be false negative.

Objective:To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk.Methods:A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95% CI after adjustment for covariates. Results:The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [ OR (95% CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95% CI: 1.01-1.30), P=0.03. Conclusions:The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.

Objective:To analyze the clinical characteristics of patients with novel coronavirus pneumonia (COVID-19) and the factors influencing mild cases developing into severe cases, so as to provide a basis for clinical screening, prevention and treatment of potential severe cases.Methods:Retrospective analysis was performed on the clinical characteristics of 168 cases who were admitted to two tertiary general hospitals in Anhui province and diagnosed with COVID-19 from January 20 to March 4, 2020. According to the classification criteria in the COVID-19 diagnosis and treatment program (trial version 6) issued by the National Health Commission, the mild and common cases were classified as the mild group ( n=137), and the severe and critical cases were classified as the severe group ( n=31). The general data, epidemiological history, clinical manifestations, laboratory examination and imaging indexes of the two groups were compared. Univariate analysis was performed. Then multivariate Logistic regression analysis was conducted on the factors with statistically significant differences in univariate analysis to obtain independent influencing factors of the occurrence of severe COVID-19. Results:Among the 168 COVID-19 patients, 95 were male and 73 were female, with an average age of 42.6±15.8 years old. The mean age of the mild group was younger than that of the severe group (40.5±15.5 vs 51.6 ±14.1, P<0.01). The proportion of patients combined with hypertension (29.0% vs 10.9%), diabetes (25.8% vs 2.2%, P=0.005) and two or more underlying diseases (29.0% vs 4.4%, P=0.006) in the severe group were significantly higher than those in the mild group. In the severe group, the proportion of patients receiving initial treatment in Medical institutions below secondary hospitals was significantly higher than that in the mild group ( P<0.01), and the time between symptom onset and diagnosis was longer [(8.00±3.27) d vs (6.49±3.90) d, P=0.048]. There was no significant difference in the initial symptoms between the mild group and the severe group. However, the body temperature was higher in the severe group [(38.80±0.67)℃ vs (37.9±0.60)℃, P<0.01]. At the time of admission, the lymphocyte percentage of the severe group was significantly lower than that of the mild group [(18.20±9.13)% vs (24.43±10.43)%, P<0.01], while C-reactive protein, interleukin-6 (IL-6), D-dimer, LDH, aspartate and aminotransferase were significantly higher than that of the mild group ( P<0.01). CT imaging showed that 11 (8%) patients in the mild group had lesions confined to a single lobe of the lung, while all patients in the severe group had multi-lobe lesions ( P<0.01). All the 168 COVID-19 patients in this study were cured, and the length of hospital stay in the severe group was significantly longer than that in the mild group [(24.71±7.72) d vs (20.28±7.67) d, P=0.021]. According to multivariate binary Logistic regression analysis, age ( P=0.042), diabetes ( P=0.021), body temperature at admission ( P=0.001), and IL-6 measured at admission ( P=0.008) were independent factors affecting COVID-19 to severe progress. Conclusions:Strengthening the professional knowledge training of primary hospitals is helpful for early diagnosis of COVID-19. Patients with older age, combined with diabetes, high initial fever and significantly increased IL-6 level are more possibly to develop into severe disease. Early identification and prevention should be carried out.

Objective:To investigate the expression changes of SKOV3 and MRTFA in ovarian cancer and their effects on tumor cell proliferation and invasion.Methods:91 cases of patients with ovarian cancer admitted to our hospital from Jun. 2017 to May. 2019 were enrolled in this study. The relationship between MRTFA mRNA expression and clinical characteristics in ovarian cancer tissues was analyzed. The ovarian cancer SKOV3 cells were cultured and grouped, and the proliferation activity of ovarian cancer SKOV3 cells was detected by MTT. The invasive ability of SKOV3 cells was determined by Transwell method, and the expression of MRTFA protein in SKOV3 cells was determined by Western blot.Results:The relative expression of MRTFA mRNA in ovarian cancer tissues was significantly higher than that in adjacent tissues ( P<0.05) . The relative expression of MRTFA mRNA in ovarian cancer tissues with tumor diameter <10 cm, FIGO stage I-II stage, moderately high differentiation and no lymph node metastasis was lower than that with tumor diameter≥10cm, FIGO stage III-IV stage, poor differentiation, lymph node metastasis in patients with ovarian cancer ( P<0.05) . The absorbance values of ovarian cancer SKOV3 cells in MRTFA intervention group were lower than those in the control group and the negative control group at 24 h, 48 h, 72 h and 96 h ( P<0.05) . Conclusions:The expression of MRTFA is abnormally increased in ovarian cancer. The specific inhibition of MRTFA protein expression can block the proliferation and invasion of SKOV3 cells. The mechanism of action may be related to the transformation process of SRF induced epithelial mesenchyme.

Objective:To explore abnormal microstructural changes of white matter in patients with white matter lesions(WML) using diffusion tensor imaging(DTI), and to determine the association of such abnormalities of DTI parameters with executive function.Methods:Totally 34 patients with WML were recruited from the department of Neurology, Beijing Tiantan Hospital, Capital Medical University from March 2012 to May 2019.All patients with WML were scored with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA), and assessed with Montreal cognitive assessment (MoCA) and clinical dementia rating(CDR). They were divided into WML-cognitive normal group, WML-vascular cognitive impairment-non dementia group and WML-Dementia group.The Stroop color and word test (SCWT), trail making test-A (TMTA), digit symbol test and verbal fluency test were carried out to evaluate executive function.In addition, the healthy elderly without WML lesions were selected as the control group after they were examined by MRI, and all brains of the subjects went through DTI with Siemens 3.0 T MR.The data were collected and analyzed by voxel based analysis (VBA). The anisotropy and mean diffusion coefficient of DTI in the region of interest (ROI) and other regions in the brain were studied in the four groups, and their correlation with scores of executive function in WML patients was analyzed.Results:(1)In these executive function test, there were significant differences between the patients with cognitive impairment (WML-VAD group, WML-VCIND group) and normal cognition group(WML-CN group, NC group), such as SCWT(B)(65.54±6.24 vs 43.67±0.95, 76.75±2.13 vs 43.67±0. 95, 65.54±6.24 vs 43.66±1.81, 76.75±2.13 vs 43.66±1.81), SCWT(C)(88.58±6.76 vs 61.63±1.31, 96.37±1.47 vs 61 63±1.31, 88.58±6.76 vs 66.31±8.19, 96.37±1.47 vs 66.31±8.19), TMTA(40.47±2.76 vs 30.92±0.47, 44.24±1.43 vs 30.92±0.47, 44.24±1.43 vs 31.99±2.07, 40.47±2.76 vs 31.99±2.07), TMTB(88.66±6.55 vs 80.34±0.61, 96.70±1.72 vs 80.34±0.61, 88.66±6.55 vs 83.10±5.91, 96.70±1.72 vs 83. 10±5.91), Digit Symbol Test(39.25±5.63 vs 47.00±2.55, 31.27±3.93 vs 47.00±2.5, 39.25±5.63 vs 48.86±4.34, 31.27±3.93 vs 48.86±4.34) and Verbal Fluency Test(8.94±1.00 vs 11.71±0.47, 6.64±0.81 vs 11.71±0.47, 8.94±1.00 vs 10.86±0.69, 6.64±0.81 vs 10.86±0.69) scores ( P<0.05); In the patients with cognitive impairment, there were significant differences between WML-VAD group and WML-VCIND group, such as SCWT(B), SCWT(C), TMTA, TMTB, digit symbol test and verbal fluency test scores ( P<0.05); There were significant differences between WML-CN patients and NC group in the scores of SCWT (C), verbal fluency test( P<0.05). (2)FA values in the genu of corpus callosum and the inferior longitudinal fasciculus were negatively correlated with the time of SCWT (B), SCWT (C) and the TMTA( r=-0.436--0.471), but positively correlated with the scores of digit symbol test and verbal fluency test( r=0.428-0.573). MD values in the genu of corpus callosum, the superior/inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus were positively correlated with the time of SCWT (B), SCWT (C) and TMTA( r=0.432~0.609), but negatively correlated with the scores of digit symbol test and verbal fluency test( r=-0.424--0.630, all P<0.003125 after emendation). Conclusion:The executive function of patients with WML-Dementia decreases significantly.The more serious the damage of white matter microstructure, the more serious the damage of executive of function.

Objective To assess the safety of infliximab (IFX) treatment in patients with Crohn's disease(CD).Methods From January 2009 to May 2018,at inflammatory bowel disease (IBD) center of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,486 CD patients received the treatment of IFX were enrolled and their clinical data were collected.Univariate and multivariate regression of binary logistic were performed for statistical analysis.Results The median follow-up duration was 31.1 months (12.0 months to 40.0 months).The median duration of IFX therapy was 13.0 months (7.0 months to 21.0 months).Among 486 patients,98 (20.16％) patients reported adverse effects,and 12 (2.47％) patients discontinued the therapy because of adverse effects.Acute infusion reaction was the most common adverse effect in CD patients who received IFX treatment accounting for 41.84％ (41/98) of all the adverse effects,and the incidence was 8.44％.Thirty-nine patients had mild and moderate infusion reaction,and all improved after symptomatic treatment (eight patients discontinued IFX therapy because of recurrent infusion reaction).Two patients developed severe infusion reaction as allergic shock,and both relieved after emergency rescue.Four patients developed late-phase allergic reactions.Among 486 patients,39 (8.02％) patients had infections,including infections of Clostridium difficile,cytomegalovirus,herpeszoster virus,Mycobacterium tuberculosis,and other opportunistic pathogens.There was no cases of infection related death.Thirty-six patients continued with IFX treatment after infection controlled.Among 486 patients,14 (2.88％) patients had severe infection,and all the cases improved after anti-infection treatment.Twenty-seven CD patients with hepatitis B virus (HBV) infection received anti-viral treatments,no active HBV infection was observed.Colon adenocarcinoma was found in one patient under colonoscopy at 22 months after discontinuation of IFX therapy.There were six patients with the history of benign tumors,and no evidence of recurrence,progress or malignancy during treatment.In terms of other rare adverse effects in 486 patients,there were eight (1.64％) patients with liver function injury,two (0.41％) patients with anemia,one (0.21％) patient with peripheral neuropathy,and four (0.82％) patients with skin lesion.Prolonged duration of IFX therapy,without combination of immune-suppressors and with increased baseline body mass index (BMI) were the risk factors of acute infusion reactions.Prolonged duration of IFX therapy and with low baseline albumin level were the risk factors of infections.Conclusions IFX is generally safe as the treatment for CD patients,and its adverse effects can be clinically controlled.Screening before therapy and monitoring during therapy may reduce the risks of adverse effects.