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 quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Humans ; Aged ; Processing Speed ; Cross-Sectional Studies ; Cognition ; Hearing Loss/psychology* ; Cohort Studies ; Cognitive Dysfunction

Objective:To analyze the clinical characteristics and predictive factors of SSc associated heart disease.Methods:The clinical data of patients with SSc from January 2016 to December 2021 in Ningbo Medical Center Lihuili Hospital were collected. Aight healthy controls come from the medicial examination center. They were divided into a positive group and a negative group based on whether heart involvement was present or not. The clinical manifestations of the two groups were compared by t test, Wilcoxon signed rank test and χ2 test and Logistic regression or ROC curve was used to analyze the prognostic risk of SSc associated heart disease. Then the transcriptome sequencing was used to analyze the differential gene expression. Results:①A total of 75 SSc patients were treated in our hospital, of which 6 patients with overlap syndrome and 1 patient with congenital heart disease were excluded. The clinical data of 68 patients were analyzed including 16 patients in the positive group and 52 patients in the negative group. Among the 16 patients with cardiac involvement, 12 patients (75.0%) had abnormal electrocardiogram, 9 patients (56.2%) with heart valve disease, 8 patients (50.0%) with abnormal cardiac structure and 8 patients (50.0%) with pericardial effusion. The biomarkers were elevated in 10 cases (83.3%). ②Univariate analysis showed that the positive group had a longer course of disease [120(11.2, 132) months vs 48(24, 90)months, Z=-2.08, P=0.037], and the rate of pulmonary arterial hypertension (50.0% vs 11.5%, χ2=11.07, P<0.001) and renal insufficiency(50.0% vs 3.8%, χ2=20.78, P<0.001) in the positive group were significantly higher than those in the negative group. Further Logistic regression analysis revealed that long course of disease [ OR (95% CI) =1.011 (1.001, 1.021), P=0.031], pulmonary arterial hypertension [ OR (95% CI) =5.431, 95% CI (1.065, 27.710), P=0.042] and renal insufficiency [ OR (95% CI) =30.444 (4.139, 223.938), P<0.001] were risk factors for SSc associated heart disease. ③Nail-fold videocapillaroscopy (NVC) was checked in 63 patients. The difference of abnormal NVC changes between the two groups was statistically significant (93.3% vs 58.3%, χ2=5.87, P=0.013). The total number of capillaries in the positive group was significantly less than that in the negative group [3.5(2, 4.8) vs 6 (5, 7), Z=-2.97, P=0.003]. Further ROC curve analysis showed that the total number of capillaries less than 4.5 predicted the occurrence of cardiac involvement (sensitivity was 80.0%, specificity was 83.8%), and the area under the ROC curve (95% CI) was 0.805 (0.061, 1.000, P=0.003).④The transcriptome of a total of 11 SSc patients (including 6 in the positive group and 5 in the negative group) and 8 healthy controls were analyzed to obtain the synchronously down regulated gene TNFRSF13B. The differences between the three groups were statistically significant ( χ2=11.88, P=0.003), especially in the positive group and the healthy controls( χ2=11.19, P=0.004). Conclusion:SSc patients with long course of disease accompanied by PAH and renal insufficiency are prone to have heart involvement. Early capillary endoscopy is also helpful to predict the risk of heart involvement. Moreover, TNFRSF13B genetic testing is helpful but further study is needed.

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

Objective:To study the macrolides resistance of Mycoplasma pneumoniae(MP) in Suzhou area, and try to explore the relationship between drug resistance and refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods:From a series of hospitalized children who were diagnosed as Mycoplasma pneumoniae pneumonia (MPP) from October 2013 to September 2014 in Suzhou area, 48 children were treated with Azithromycin (10 mg/kg, once a day, intravenous drip for 5-7 days), and the clinical symptoms and chest imaging were still progressing so they were clinically diagnosed as RMPP, and 34 children who were successfully treated with macrolides antibiotics (MA) were clinically diagnosed as general MPP (GMPP). MP DNA was extracted from the airway secretion of children in the two groups, and the point mutations of 2063 and 2064 of 23S rRNA were sequenced, and according to the MP 23S rRNA sequencing results, the children were divided into macrolides antibiotic resistant MP group (MRMP) and macrolides antibiotic sensitive MP group (MSMP). The clinical characteristics of the two groups were compared. Results:In the MRMP group, the incidence of RMPP was 62.2% (46/74 cases), while in MSMP group, the incidence of RMPP was 25.0% (2/8 cases). The point mutation of MP 23S rRNA had no significant effect on the occurrence of RMPP ( χ2=2.719, P=0.099). Compared with MRMP group, MSMP group presented shorter fever time and less glucocorticoid use.No significant differences between the two groups were found in chest imaging examination, as well as some laboratory results, including the total number and classification of white blood cell (WBC), C-reactive protein (CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB). Conclusions:The fever duration of MPP lasted more than 1 week, suggesting the possibility of macrolides resistance of MP, but macrolides resistance did not aggravate the occurrence of RMPP.It is unreliable to judge the MRMP by chest imaging features and laboratory results.

Objective:To assess the health status and health service utilization of children born to syphilis infected mothers during pregnancy, in order to prevent mother-to-child transmission of syphilis to the newborns.Methods:Women with maternal syphilis were studied by trained researchers via phone calls, in Shanghai during 2014-2015. Data related to demographics, status of infection and health care, utilization by both mothers and their children were collected through specifically designed questionnaires. Non-parametric tests including chi-square were used to assess the health status and health service utilization of children born to mothers with different demographic and socioeconomic characteristics.Results:A total of 495 children born to mothers with maternal syphilis were recruited from 1 000 syphilis infected parturient women. A total of 61 out of the 495 children were diagnosed as having congenital syphilis (57 children were diagnosed at birth and another 4 were diagnosed during the follow-up period). Children born to women who received syphilis treatment during pregnancy were at lower risk on congenital syphilis ( χ2=7.214, P=0.027). 37.8 % of the children were reported to have had different illnesses in the past three months, mainly involving upper respiratory infections (32.3 %) or diarrhea (3.6 %). Children diagnosed with congenital syphilis showed a higher prevalence of different kinds of diseases, compared to those without congenital syphilis (47.5 % vs. 36.6 %). 81.6 % of the children had received regular child health care services. Subjects with the following factors as: being immigrant, with lower education, unemployed, unmarried and multipara, were related to the less use of regular child healthcare services. Only 39.7 % of the parents would inform the care-takers about the risk of congenital syphilis infection of their own children at the child health care centers. Mothers with residency of Shanghai, having higher education level and employed, were less willing to inform doctors about the risk of congenital syphilis infection of their children. Conclusions:Loss to follow-up among children born to syphilis infected pregnant women remained a serious problem. Few parents would be willing to inform the healthcare takers that their children are at risk of syphilis, when receiving child health care services at the centers. It was necessary to integrate the congenital syphilis follow-up programs into the routine child care services so as to timely diagnose and treat the patients with congenital syphilis.

Objective: To analysis the pathogenic mutation and the clinical characteristics of a three generation family with congenital pulverulent cataract. Methods: A congenital cataract family was chosen from the First Affiliated Hospital of AnHui Medical University, 5 ml peripheral blood was obtained from each family member to extract genomic DNA.Next generation sequencing was used to detect the mutation in proband (Ⅱ5), Ⅱ6 and Ⅲ8, and Sanger sequencing was applied to verify pathogenic mutation in the whole family members.The mutation site was compared with the gene sequence of 10 000 normal Chinese.PolyPhen-2 and SIFT were applied to analysis the alteration on the protein structure and function and its possible pathogenesis.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of AnHui Medical University (NO.PJ2017-5-17). All patients signed informed consent. Results: The pedigree consisted of 19 members of three generations, including 10 patients and 9 normal family members.Heterozygous mutation of GJA3 gene c. 427G>A (p.G143R) was detected in all patients of the pedigree, but was not found in normal members of the pedigree and 10 000 normal Chinese.The score calculated from SIFT and PolyPhen-2 indicated that the mutation probably had malignant effect on normal protein structure, Swiss-model website analysis showed that the mutation likely altered the secondary structure of the protein CX 46 by reducing an α-helix between 107-115 amino acids.Meanwhile, c.1325-1G>T mutation of HSF4 gene were detected in Ⅱ5 and Ⅲ8, which was not found in other family members and 10 000 normal Chinese.HSF and MaxEntScan results showed that the mutation probably had serious effect on the splicing of mRNA.The cataract development rates of Ⅱ5 and Ⅲ8 were faster than that of the same age in the same generation of the pedigree, and the morphology of lens opacity was changed. Conclusions The heterozygous c. 427G>A mutation in GJA3 gene is responsible for pulverulent cataract in this family, meanwhile the c. 1325-1G>T mutation in HSF4 gene may change the type of phacoscotasmus and accelerate the progress of disease.

Objective    To explore the use of comprehensive treatment including drugs, devices and electrophysiology for heart failure patients with surgical indications. Methods    We collected the clinical data of 65 consecutive cardiac surgical patients with chronic left ventricular dysfunction in our department between March 2014 and May 2016. There were 49 males and 16 females with an average age of 61.3±11.4 years ranging from 37 to 80 years. Their left ventricular ejection fraction was less than 40%. Patients with ventricular dysfunction caused by acute myocardial infarction were excluded. A comprehensive treatment strategy was performed according to patients’ individual disease. Results    Fourty patients underwent cardiopulmonary bypass with asisting time of 55-400 (148.1±69.8) min; 35 patients needed cross-clamping with time of 44-203 (95.7±39.6) min. Intra-aortic balloon pump (IABP) was assisted in 3 patients. Two patients died in hospital. During the follow-up of 13.4 months, the patients’ cardiac function significantly improved and the heart size reduced. Two patients died and two were readmitted for heart failure. Four patients underwent cardiac pacemaker implantation. Other patients with unstable symptoms were stabilized after medical dose adjustment. Conclusion    Under the concept of neuroendocrine inhibition, the comprehensive treatment for heart failure can effectively reduce surgical mortality and improve the patient’s quality of life.