OBJECTIVETo obtain the polymorphic data of short tandem repeat(STR) loci of D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the association of these four STR loci with insulin-dependent diabetes mellitus(IDDM).

METHODSThe polymorphisms of the four STRs were studied by polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients with IDDM.

RESULTSSeven alleles at D15S657 locus, 5 alleles at D11S1369 locus, 7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and allele A(4) at D6S2420 locus were increased significantly in patients with IDDM, compared to those in the control group.

CONCLUSIONThe four STRs, used as genetic markers, were suitable for case-control study, forensic medicine identification and population genetic study. There is an association between the polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.

Adult ; Aged ; China ; ethnology ; Diabetes Mellitus, Type 1 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Tandem Repeat Sequences

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.
Male ; Humans ; Female ; alpha-Fetoproteins ; Stomach Neoplasms/genetics* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Adenocarcinoma/pathology* ; Biomarkers, Tumor/genetics* ; DNA Helicases/genetics* ; Nuclear Proteins ; Transcription Factors/genetics* ; Glypicans

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.
Male ; Female ; Humans ; Middle Aged ; Adult ; Aged ; Aged, 80 and over ; Gastrointestinal Stromal Tumors/surgery* ; Receptor, Platelet-Derived Growth Factor alpha/genetics* ; Retrospective Studies ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-kit/genetics*

In clinical follow-up studies, hazard ratio (HR) is routinely used to quantify the differences between-groups, however, it is being estimated by the Cox procedure. HR, the ratio of two hazard functions has abstract meaning only and is in lack of the context to give an intuitive explanation of the survival of patients and the assumption of proportional hazards (PH) must be satisfied. Under this context, the restricted mean survival time (RMST) can be used as a relatively effective measure or index of statistics. This paper introduces the RMST-based statistical analysis methods, including estimation of RMST and its difference, hypothesis testing and regression analysis. The application of RMST in data analysis is also introduced. All the evidence demonstrates that RMST can be used as an effective analytical tool with straightforward interpretation. RMST is also more effective than HR in comparing differences between groups, when non-PH is observed. Therefore, RMST is suggested to be stated along with HR in the process of disease efficacy evaluation and prognosis analysis. Cooperation and complement of the two, a precise reflection on the characteristics of data can be expected.
Clinical Trials as Topic ; Endpoint Determination/methods* ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Survival Rate/trends* ; Treatment Outcome

Acute Lung Injury ; Animals ; Autophagy ; Explosions ; Lung ; Rats ; Rats, Sprague-Dawley

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ²=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.
Humans ; Prognosis ; Retrospective Studies ; Neoplasm Staging ; Extranodal Extension/pathology* ; Survival Analysis ; Rectal Neoplasms/surgery* ; Lymph Nodes/pathology*

Humans ; Frozen Sections ; Adenoma/diagnosis* ; Bronchial Neoplasms/surgery*

Humans ; Lung Transplantation/adverse effects* ; Risk Factors

Objective: Total mesorectal resection (TME) is difficult to perform for rectal cancer patients with anatomical confines of the pelvis or thick mesorectal fat. This study aimed to evaluate the ability of pelvic dimensions to predict the difficulty of TME, and establish a nomogram for predicting its difficulty. Methods: The inclusion criteria for this retrospective study were as follows: (1) tumor within 15 cm of the anal verge; (2) rectal cancer confirmed by preoperative pathological examination; (3) adequate preoperative MRI data; (4) depth of tumor invasion T1-4a; and (5) grade of surgical difficulty available. Patients who had undergone non-TME surgery were excluded. A total of 88 patients with rectal cancer who underwent TME between March 2019 and November 2021 were eligible for this study. The system for scaling difficulty was as follows: Grade I, easy procedure, no difficulties; Grade II, difficult procedure, but no impact on specimen quality (complete TME); Grade III, difficult procedure, with a slight impact on specimen quality (near-complete TME); Grade IV: very difficult procedure, with remarkable impact on specimen quality (incomplete TME). We classified Grades I-II as no surgical difficulty and grades III-IV as surgical difficulty. Pelvic parameters included pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the difficulty of TME, and a nomogram predicting the difficulty of the procedure was established. Results: The study cohort comprised 88 patients, 30 (34.1%) of whom were classified as having undergone difficult procedures and 58 (65.9%) non-difficult procedures. The median age was 64 years (56-70), 51 patients were male and 64 received neoadjuvant therapy. The median pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance were 12.0 cm, 11.0 cm, 8.6 cm, 4.9 cm, 12.6 cm, 3.7 cm, 3.0 cm, 13.3 cm, 10.2 cm, and 12.2 cm, respectively. Multivariable analyses showed that preoperative chemoradiotherapy (OR=4.97,95% CI: 1.25-19.71, P=0.023), distance between the tumor and the anal verge (OR=1.31, 95% CI: 1.02-1.67, P=0.035) and pubic tubercle height (OR=3.36, 95% CI: 1.56-7.25, P=0.002) were associated with surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC = 0.795, 95%CI: 0.696-0.895). Conclusion: Our research demonstrated that our system for scaling surgical difficulty of TME is useful and practical. Preoperative chemoradiotherapy, distance between tumor and anal verge, and pubic tubercle height are risk factors for surgical difficulty. These data may aid surgeons in planning appropriate surgical procedures.
Humans ; Male ; Middle Aged ; Female ; Retrospective Studies ; Laparoscopy/methods* ; Pelvis/pathology* ; Rectal Neoplasms/pathology* ; Magnetic Resonance Imaging ; Treatment Outcome