Malignant peripheral nerve sheath tumor: a clinicopathological analysis / 中华病理学杂志

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.

Epidemiologic survey on the prevalence and distribution of infants' common gastrointestinal symptoms in 7 cities in China: a population-based study / 中华流行病学杂志

Objective: Regurgitation, infantile colic, and functional constipation are common gastrointestinal symptoms in childhood, the aim of this study was to explore the prevalence and distribution of these symptoms in China. Methods: A screening program in infants aged 0 to 3 years selected through stratified cluster random sampling was carried out in 7 cities in China. Questionnaires were filled, and then diagnosis were made according to Rome Ⅳ criteria. Areas, (urban-rural), age and gender distribution of prevalence of childhood common gastrointestinal symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged 0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with age, and differences among different age groups showed significant. For infantile colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of infantile colic was 7.3%. The prevalence of infantile colic was the highest in infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of all the infants, functional constipation was diagnosed in 1 755 infants with the prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3 months (6.2%), and the highest prevalence was in infants aged 30 to 36 months (10.0%). The differences in different age group were significant. Conclusion: Symptoms of regurgitation, infantile colic, and functional constipation are common in infants in China, with age specific difference in prevalence of the symptoms.

A study on the burden and causes of hospitalization and deaths in Shenzhen, between 1995 and 2014 / 中华流行病学杂志

Objective: Data from the surveillance program was collected, to analyze the situation of hospitalization and cases of death with recorded causes, in Shenzhen, from 1995 to 2014. Situation of hospitalization and causes of deaths were studied in Shenzhen which had been a fast-developing city with growing number of immigrants so as to provide reference for decision-making on related prevention and control strategies. Methods: Data on hospitalizations and deaths collected from the surveillance program, were classified by both International Classification of Diseases (ICD)- 9 and ICD-10. A database was constructed with methods on related descriptive and trend analysis. Results: Around 6.3 million inpatients were seen in the past two decades in Shenzhen. The top five diseases for hospitalization were pregnancy childbirth and puerperium complications, respiratory diseases, injury and poisoning, digestive system diseases and circulatory system diseases, that accounting for 68.4% of all the hospitalization burden. The number of inpatients increased annually, with an 11 times increase during the past two decades. Proportions for pregnancy childbirth and puerperium complications, circulatory system diseases and urinary system diseases all showed increasing (χ(2)=53 806.94, 6 893.95 and 15 383.14, P<0.01), while proportions for injuries and poisoning, respiratory diseases, digestive system diseases showed a declining trend (χ(2)=131 480.09,1 711.84 and 11 367.66, P<0.01). Number of cumulative inpatient deaths exceeded 60 000, with the top five causes as malignant tumor, circulatory system diseases, injury and poisoning, respiratory system diseases and digestive system diseases, that accounting for 82.28% of all the inpatient deaths. Deaths due to circulatory system diseases, injury and poisoning increased and then decreased. Malignant tumor and respiratory diseases-induced deaths showed an increasing trend (χ(2)=1 546.48, 309.55, P<0.01), while induced deaths from disease of the other systems showed slight changes. The overall case fatality rate showed an annual decline (χ(2)=4 378.63, P<0.01), from 2.23% in 1995 to 0.74% in 2014, with mortality attribute to tumor, circulatory system disease decreased significantly. Conclusions: Shenzhen had been under an ageing transition, with relatively young population living in the city. Chronic diseases such as tumor gradually had become the major causes for heavy hospitalization burden on the population of Shenzhen.

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues.</p><p><b>DATA SOURCES</b>This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation."</p><p><b>STUDY SELECTION</b>Original articles and critical reviews on the topics were selected.</p><p><b>RESULTS</b>Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified.</p><p><b>CONCLUSIONS</b>In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.</p>