Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Neurofibrosarcoma ; Neurofibromatosis 1 ; Histones ; Genes, p53 ; Nerve Sheath Neoplasms

Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.
Male ; Female ; Humans ; Child ; Child, Preschool ; Pseudarthrosis/congenital* ; Follow-Up Studies ; Retrospective Studies ; Tibia/surgery* ; Neurofibromatosis 1 ; Tibial Fractures/surgery*

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*

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

Background: Intertrochanteric hip fractures are among the most common and most expensive diagnoses in the Medicare population. Liposomal bupivacaine is a novel preparation of a commonly used analgesic agent that, when used intraoperatively, decreases narcotic requirements and hospital length of stay and increases the likelihood of discharge to home. The purpose of this investigation was to determine whether there was an economic benefit to utilizing intraoperative liposomal bupivacaine in patients with fragility intertrochanteric hip fractures in comparison to a group of patients who did not receive liposomal bupivacaine. Methods: This is a retrospective observational study performed at two academic medical centers. Fifty-six patients with intertrochanteric hip fractures treated with cephalomedullary nail implant who received standard hip fracture pain management protocol were compared to a cohort of 46 patients with intertrochanteric hip fractures who received additional intraoperative injections of liposomal bupivacaine. All other standards of care were identical. A cost analysis was completed including the cost of liposomal bupivacaine, operating room costs, and discharge destination. Statistical significance was set at p < 0.05. Results: Although the length of hospital stay was similar between the two groups (3.2 days vs. 3.8 days, p = 0.08), patients receiving intraoperative liposomal bupivacaine had a lower likelihood of discharge to a skilled nursing facility (84.8% vs. 96.4%, p = 0.002) and a longer operative time (73.4 minutes vs 67.2 minutes, p = 0.004). The cost-benefit analysis indicated that for an investment of $334.18 in the administration of 266 mg of liposomal bupivacaine, there was a relative saving of $1,323.21 compared to the control group. The benefit-cost ratio was 3.95, indicating a $3.95 benefit for each $1 spent in liposomal bupivacaine. Conclusions Despite the increased initial cost, intraoperative use of liposomal bupivacaine was found to be a cost-effective intervention due to the higher likelihood of discharge to home during the postoperative management of patients with intertrochanteric hip fractures.

Animals ; Benzo(a)pyrene/toxicity* ; Cytokines ; Dibutyl Phthalate/toxicity* ; Female ; Liver ; Male ; NF-kappa B ; Rats ; Rats, Sprague-Dawley

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: To understand the characteristics of HIV infected persons without long term disease progress [also known as long term non-progressors (LTNPs)], and related factors in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data of persons living with HIV and receiving no antiretroviral therapy in Guangxi by the end of 2016 were collected from the national HIV/AIDS comprehensive control and prevention information system of China. Results: By the end of 2016, there were 313 LTNPs in Guangxi, accounting for 2.3% of those being reported for more than 10 years, 5.4% of those being reported for more than 10 years and surviving, and 26.6% of those being reported for more than 10 years, surviving and receiving no antiretroviral therapy. Among the LTNPs, 87.2%(273) were men, 94.9% (297) were aged ≤ 40 years, 32.3% (101) were farmers, 55.6% (174) were single, divorced or widowed, 69.3% (217) were of Han ethnic group, 68.1% (213) were injecting drug users, and 52.1% (163) were from custody facilities. Multiple logistic regression analysis indicated that factors associated with delayed disease progression included age ≤40 years (compared with age >40 years, aOR=1.55, 95%CI: 1.31-3.12) and injection drug use (compared with sexual transmission, aOR=1.23, 95%CI: 1.10-1.74). Conclusions: A number of LTNPs existed in HIV-infected individuals in Guangxi. Further research are needed to identify the related factors, and it is necessary to conduct large sample size studies on host immunology, genetics and the virology of HIV to explore the related mechanism.
Adolescent ; Adult ; Age Distribution ; China/epidemiology* ; Drug Users/statistics & numerical data* ; Ethnicity/statistics & numerical data* ; HIV Infections/ethnology* ; Humans ; Male ; Socioeconomic Factors

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.
Adenoma/prevention & control* ; Aged ; China/epidemiology* ; Colonoscopy/statistics & numerical data* ; Colorectal Neoplasms/prevention & control* ; Early Detection of Cancer/methods* ; Female ; Humans ; Immunochemistry ; Male ; Mass Screening/statistics & numerical data* ; Middle Aged ; Occult Blood ; Predictive Value of Tests