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In May 2022, cases of monkeypox were reported in non-monkeypox endemic countries such as Europe and the United States. As of 26 May, a cumulative total of 257 laboratory-confirmed cases and approximately 120 suspected cases had been reported to WHO from non-monkeypox endemic countries. This event immediately caused great concern and alarm to the WHO and national virologists. This paper aims to summarize the epidemiological and clinical features of previous monkeypox virus infections and the current local outbreaks in non-monkeypox endemic countries and propose countermeasures to control the current localized infections in non-monkeypox endemic areas as soon as possible. We reviewed the literature and websites related to monkeypox. We searched Google Scholar, PubMed, Web of Science, Embase, and African Journals Online using the medical subject terms "monkeypox", "monkeypox virus", "monkeypox outbreak", "non-monkeypox endemic areas", "clinical features", "epidemiology", "transmission", and "infection". We found that monkeypox is a zoonotic disease of forest animals that has occurred mainly in West and Central Africa since the first case was reported in the Congo in 1970, with occasional cases spreading to countries such as the United States and Europe. It is common among students, housekeepers, hunters, farmers and housewives. It is more common in males than females, occurs below middle age, and is more common in children under 10. The incubation period is 5 to 21 days, and the rash usually appears within 1 to 3 days after the onset of fever. Clinical manifestations include fever, rash, swollen lymph nodes, headache, muscle pain and unusual weakness. Most patients have mild symptoms that last from 2 to 4 weeks. The source of the sudden outbreak in Europe and the United States is currently unknown and occurs mostly in homosexuals who have sex with men (MSM). Outbreaks of monkeypox virus infection in non-monkeypox endemic areas have received widespread attention and focus. We believe that a scientific response to the transmission route of monkeypox virus and, where necessary, vaccination of high-risk groups against the monkeypox smallpox will control infection in non-monkeypox endemic areas.

Polycystic ovary syndrome (PCOS) is often difficult to diagnose in adolescents. Recent recommendations and concepts regarding the diagnosis and treatment of PCOS in the adolescent girl are considered.The diagnosis of PCOS in adolescents should be primarily based on clinical and biochemical signs of hyperandrogenism and presentation with irregular menses. Because of the similarity of normal pubertal development and features of PCOS, the diagnosis should be deferred until at least 2 years following menarche. For girls who do not fulfill the diagnostic criteria, the focus should be on treatment of symptoms.PCOS is a complex, multifaceted disorder, and should be diagnosed and treated in adolescents after taking into consideration the patient's full diagnostic picture, metabolic risks, and individual concerns, to both avoid overdiagnosis but yet be able to provide early and meaningful interventions.

To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression.MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined.MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6.MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.

Premature adrenarche (PA) has been assumed to be a benign variant of normal pubertal development. Yet, current collective information suggests associations between PA and potential risks for development of polycystic ovary syndrome and adult diseases such as the metabolic syndrome. Adrenarche refers to the increased secretion of the adrenal androgen precursors DHEA, DHEAS, and androstenedione, which normally occurs in children at age 6-8 years. PA may be identified clinically by early pubarche, which is defined as the development of pubic or axillary hair before 8 years in girls or 9 years in boys. This paper will consider adrenal steroidogenesis, genetic markers, neurobiological changes, skeletal maturation, and associations with adult disorders. The differential diagnosis will be reviewed because PA remains a diagnosis of exclusion. Finally, synthesis of current knowledge regarding PA, suggestions for evaluation, management, and treatment are offered.

Objective To investigate the application of the comprehensive use of multiple genetic markers in full and half sibling relationship testing through the identification of a case of suspected sibling relationship. Methods Genomic DNA were extracted from bloodstain samples from 4 subjects （ZHANG-1, ZHANG-2, male; ZHANG-3, ZHANG-4, female）. Autosomal STR loci, X-STR, Y-STR loci and polymorphisms of mtDNA HV-Ⅰ and Ⅱwere genotyped by EX20 STR kit, X19 kit, Data Y24 STR kit, and Sanger sequencing, respectively. Results According to autosomal STR based IBS scoring results, full sibling relationships were indicated among ZHANG-2, ZHANG-3 and ZHANG-4, but those were not indicated between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4. According to autosomal STR based FSI and HSI, with ITO method and discriminant function method, full sibling relationships among ZHANG-2, ZHANG-3 and ZHANG-4 were indicated, and half sibling relationships between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4 were also indicated. X-STR and mtDNA sequencing results showed that all the 4 samples came from a same maternal line, and Y-STR results showed that ZHANG-1 and ZHANG-2 did not come from a same paternal line, which supported the half sibling relationship between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4, verified by parental genotype reconstruction based on autosomal STR genotyping. Conclusion For the identification of sibling relationships, it is effective to have reliable results with the mutual verification and support of multiple genetic markers （autosomal STR, sex chromosomal STR and mtDNA sequence） and calculations （IBS, ITO, discriminant function method and family reconstruction）.应用多种遗传标记甄别全同胞和半同胞关系1例.目的 通过对1例全同胞关系存疑案例的鉴定，探讨多种遗传标记的综合使用在甄别同胞关系中的应用。 方法 提取4名受检者（张1、张2，男性；张3、张4，女性）血痕DNA，使用EX20 STR试剂盒扩增检验常染色体基因座，X19试剂盒扩增检验X-STR基因座，Data Y24 STR试剂盒扩增检验Y-STR基因座，一代测序技术分析线粒体DNA高变区Ⅰ和Ⅱ的SNP多态性。 结果 基于常染色体STR基因分型的IBS评分结果提示：张2、张3、张4之间存在全同胞关系，无法判断张1与张2、张3、张4之间的全同胞关系；基于常染色体STR基因分型的ITO法、判别函数法计算结果，支持张2、张3、张4之间存在全同胞关系，提示张1与张2、张3、张4存在半同胞关系；依据X-STR基因分型和线粒体DNA高变区检测结果，提示张1、张2、张3、张4为同一生母，同时Y-STR基因分型结果排除张1与张2为同一生父，进一步支持张1与张2、张3、张4为同母异父半同胞关系，并得到根据常染色体STR基因分型结果重建父母基因型的验证。 结论 对于同胞关系鉴定，需要综合应用各种遗传标记（包括常染色体STR、性染色体STR、线粒体DNA序列等），综合使用各种分析方法（包括IBS评分、ITO法、判别函数法和家系重建等），互相验证和支持，才能获得可靠的鉴定意见。.法医遗传学；遗传标记；同胞关系；短串联重复；Y-STR；DNA，线粒体.

MAGEL2 is one of five protein-coding, maternally imprinted, paternally expressed genes in the Prader-Willi syndrome (PWS)-critical domain on chromosome 15q11-q13. Truncating pathogenic variants of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild-type (WT) allele and a paternally inherited Magel2-lacZ knock-in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader-Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism-like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three-chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in-depth investigation of behavioral profiles caused by Magel2 loss-of-function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general.

To investigate the epidemiological features of heatstroke in Shaoxing, China in 2008-2014, and to provide a reference for developing prevention and control measures for heatstroke.The reports on heatstroke in Shaoxing in 2008-2014 were collected from the China Information System for Disease Control and Prevention, and the data were summarized and analyzed.A total of 1 676 heatstroke cases were reported in Shaoxing in 2008-2014, among which 1 485 cases(88.6%) were mild heatstroke and 191 cases(11.4%) were severe heatstroke. Nine persons died of severe heatstroke, and the fatality rate was 0.5%(9/1 676). Among these persons, 4(44.4%, 4/9) were the elderly living at home, 4 (44.4%, 4/9) were farmers (working outdoors), and 1(11.2%, 1/9) was unemployed. The male patients with heatstroke accounted for 66.3%(1 111/1 676), and those with severe heatstroke accounted for 13.1%(146/1 111); the female patients with heatstroke accounted for 33.7%(565/1 676), and those with severe heatstroke accounted for 8.0%(45/565); there were significant differences between male and female patients(χ(2)=9.94, P=0.002). The mean age of patients with heatstroke was 48.7±18.8 years; the mean age of male patients was 49.8±17.9 years, and that of female patients was 46.6±20.3 years, with a significant difference between the male and female patients(t=3.19, P0.001). Most of the patients experiencing heatstroke were in their forties or fifties, each accounting for 19.2%(321/1 676); in male patients who experienced heatstroke, those in their fifties accounted for the highest percentage(21.5%, 239/1 111), and in female patients who experienced heatstroke, those in their twenties accounted for the highest percentage (18.9%, 107/565). Based on stratification by age, the severity of heatstroke differed significantly between male and female patients in their forties, fifties, sixties, seventies, and eighties(P0.05). Most of the cases of heatstroke occurred in June to September, accounting for 98.9%(1 657/1 676), particularly in July and August, accounting for 87.1%(1 460/1 676).In Shaoxing, heatstroke usually occurs in summer, and most cases are mild. Middle-aged and elderly men and farmers(working outdoors) are susceptible to heatstroke, and warnings on heatstroke and emergency treatment of severe heatstroke should be enhanced.

Receptor for advanced glycation end products (RAGE) is considered a major pattern recognition receptor, which plays an important role in the development of sepsis. Increasing evidence showed an association between RAGE polymorphisms and the susceptibility to several inflammatory-related diseases. However, little is known about the clinical relationship between RAGE polymorphisms and sepsis. In this study, we analyzed the association of sepsis with three functional RAGE gene polymorphisms (rs1800624, rs1800625 and rs2070600) in a Chinese Han population (372 sepsis cases and 400 healthy controls). Significant differences were observed in the rs1800624 and rs1800625 genotype/allele distributions between the sepsis and controls, but no significant difference was observed in the rs2070600 genotype/allele. Moreover, our results also revealed a significant difference in the genotype/allele frequencies of the rs1800624 and rs1800625 polymorphisms between the sepsis and severe sepsis subtypes, the rs1800624 TT or rs1800625 TT genotype carriers exhibited a significant increase in RAGE mRNA, sRAGE, TNF-α and IL-6 expression compared with the rs1800624 AT/AA or rs1800625 CT/CC carriers in sepsis patients. Overall, this study might provide valuable clinical evidence between the RAGE gene polymorphisms and the risk or the development of sepsis.

Schistosomiasis japonica, caused by Schistosoma japonicum, is still a major public-health concern in China, afflicting thousands of people (Zhou et al., 2007; Li et al., 2009). Since 1992, when the World Bank Loan Project for Schistosomiasis Control was initiated in China, praziquantel-based chemotherapy has been used to control the disease (Chen, 2005). Unfortunately, in the long term, repeated praziquantel treatment may lead to resistance to the drug in some Schistosoma species (Fallon et al., 1995; Ismail et al., 1996; Wang et al., 2010), and the development of new schistosomicidal drugs, as alternatives to praziquantel, is therefore a priority.

Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome. However, limited data exist for pediatric patients. The aim of this study was to describe the clinical characteristics of cryptococcosis in pediatric patients.A retrospective study was conducted at West China Second University Hospital, Sichuan University. Data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis were evaluated. Clinical characteristics associated with cryptococcal meningitis and disseminated cryptococcosis were compared.Twelve cases of cryptococcal meningitis and 11 cases of disseminated cryptococcosis were identified. Seventeen cases had no underlying disease, but 6 cases had malnutrition. Only 6 cases had a history of exposure to pigeon droppings. No cases had pulmonary cryptococcosis alone. Coughing, pulmonary moist rales, swollen lymph nodes, liver and spleen, and skin rashes were seen only in disseminated cryptococcosis. The prevalence of headache and positive meningeal irritation sign was higher in cryptococcal meningitis than disseminated cryptococcosis. The proportion of increase in eosinophils was higher in disseminated cryptococcosis than cryptococcal meningitis. The primary methods used for diagnosis included cerebrospinal fluid ink staining, cerebrospinal fluid culture, blood culture, and lymph node biopsy. Two patients stopped treatment, and 21 patients received antifungal therapy. The mortality rate was 39.13%.Cryptococcosis occurs in non-HIV infected and immunocompetent children. Cryptococcosis lacks specific clinical manifestations. Disseminated cryptococcosis commonly occurs in children. Clinicians should consider a diagnosis of disseminated cryptococcosis for children who present with unexplained long-term fever, mild cough, chest imaging inconsistent with clinical symptoms, lymphadenectasis, hepatosplenomegaly, and eosinophilia.

Objective: Caesarean section rates are increasing dramatically in China. The predominant contributor to the increase in China was the unnecessary Caesarean section. The objective of this study was to estimate the excess economic burden caused by unnecessary Caesarean sections vs. vaginal delivery for Beijing and all China. Methods: The 33 476 obstetric medical case files from randomly selected 17 hospitals of Beijing in 2011 were taken for our descriptive approach. Based on the individual medical files and on a definition of what necessary and unnecessary Caesarean sections are, we sampled also the data for costs and length of stay for comparisons with vaginal deliveries. The Mann-Whitney U test and Pearson chi-square test statistics were used to test for significant difference in the analysis. Results: The Caesarean section rate was 58.5% among all deliveries and that rate of unnecessary Caesarean sections was 71.5% among all the Caesarean sections but 41.8% among all deliveries in Beijing. The hospitalisation expenses of unnecessary Caesarean sections were 472 US$ higher than that of a vaginal delivery on average. The total excess economic burden caused by unnecessary Caesarean sections can be estimated to 38.97 million US$ for Beijing and to 3.29 billion US$ all over China in 2011. This is equivalent to the annual health expenditure of over 139 575 residents in Beijing and of 11 783 120 residents in China, respectively. Conclusion: Socio-economic factors are possible reasons for the increase of unnecessary Caesarean section in China and more analytical attention should be paid to that problem in order to propose fitting practical reactions.

The Food and Drug Administration (FDA) has conducted the Total Diet Stuty (TDS) annually since 1961. The TDS is designed to monitor the US food supply for levels of toxic chemical contaminants (pesticide residues, industrial chemicals and toxic elements) and nutritional elements. Foods are generally collected four times a year, once from each of four regions of the country. The foods are prepared table-ready before being analysed. From the results of the TDS, dietary, intakes of these analytes are estimated for selected age-sex groups in the US population. This paper reports on the dietary intake of 10 nutritional and four toxic elements based on measurements made in foods collected in the TDS between 1991 and late 1996. Average daily intakes were estimated for 14 age-sex groups in the US population, as well as the contribution of specific food groups to total intakes. For most nutritional elements, teenage boys and adult males had the highest daily intakes. Intakes by infants were below the intake references for seven of 10 nutritional elements, and young girls and women had inadequate intakes of at least half the nutritional elements. Intakes by children between 2 and 10 years of age, teenage boys, and adult males met or exceeded the reference intakes for the majority of nutritional elements. Intakes by all population groups were well below the reference intakes for all toxic elements.

Most of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug eruptions. There is currently no established treatment due to a lack of controlled/blinded studies. High-dose glucocorticoids and intravenous immunoglobulins (IVIG) therapy have been widely used, but these approaches remain controversial. This study introduces a novel method by which to treat severe SJS/TEN patients who were refractory to glucocorticoids and IVIG.Seven patients with SJS and three patients with TEN were enrolled in this non-blinded, uncontrolled study. The average patient age was 8.1 years. The male to female ratio was 1:1. Hemoperfusion was conducted daily using a HA280 resin sorbent column until new skin lesions ceased appearing and the skin started healing with visible re-epithelialization.The average BSA involvement in SJS and TEN was 8.57% and 75%, respectively. The number of hemoperfusion sessions ranged from 3 to 5. Hemoperfusion led to prompt improvements in general health and halted the disease progression. All children were discharged and recovered completely. The average length of stay was 14.4 days. Four patients experienced adverse reactions: femoral vein thrombosis (N = 2), hypotension (N = 1), and cardiac palpitation (N = 1).Hemoperfusion may be a useful adjunct treatment for patients with severe SJS/TEN if the initial treatment with glucocorticoids and IVIG fails.

Genomic full-length sequences of HLA-A*03:01:01:01 and A*03:02:01, were identified in two Chinese donors.

The FDA has conducted the Total Dietary Study (TDS), a yearly market basket programme, since 1961. It is designed to monitor the levels of toxic chemical contaminants (pesticide residues, industrial and elemental contaminants) and essential nutrients in the US food supply. It also provides information on trends in dietary concentrations and exposures for the general population. Foods are collected from retail stores once a year from each of four geographic areas of the US and are analysed either after preparation/cooking or as ready-to-eat. The latest TDS (1991-1997) data show that arsenic (inorganic and organic, > or = 0.03 ppm) was found in 63 (24%) of the 261-264 foods/mixed dishes analysed. The highest concentration was found in seafood, followed by rice/rice cereal, mushrooms, and poultry. Based on the United States Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey, the estimated daily total arsenic average intakes, in microgram/day, are: 2 for infants, 23 for toddlers, 20 for 6-year-old children, 13 for 10-year-old children, 15 for 14-16-year-old boys, 21 for 14-16-year-old girls, 57 for 25-30-year-old men, 28 for 25-30-year-old women, 47 for 40-45-year-old men, 37 for 40-45-year-old women, 92 for 60-65-year-old men, 72 for 60-65-year-old women, 69 for 70-year-old men, and 42 for 70-year-old women. Of the estimated total arsenic intakes for infants, 42% arise from seafood and 31% from rice/rice cereals. Of the estimated total arsenic intakes, seafood contributes 76-90% for children (2-10-year olds), 79-85% for 14-16-year olds, and 89-96% for adults (> or = 25-30-year olds); rice/rice cereals contributes 4-8% for children, 8% for 14-16-year olds, and 1-4% for adults (> or = 25-30-year olds).

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-β1 (TGF-β1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12–15 days earlier with proteolipid protein in complete Freund’s adjuvant, were injected with 3 × 106cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-β1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-β1. The transduced cells secreted 2–4 ng/ml of latent TGF-β1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-γ were similar before and after transduction; interleukin-4 and -10 were absent. TGF-β1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-β1-transduced, antigen-activated cells, contained detectable amounts of TGF-β1 cDNA. We conclude that latent TGF-β1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.

Germanium-containing dietary supplements became popular in the 1970s in Japan and later in other countries, as elixirs for certain diseases (e.g., cancer and AIDS). Germanium is not an essential element. Its acute toxicity is low. However, at least 31 reported human cases linked prolonged intake of germanium products with renal failure and even death. Signs of kidney dysfunction, kidney tubular degeneration, and germanium accumulation were observed. Other adverse effects were anemia, muscle weakness, and peripheral neuropathy. Recovery of renal function is slow and incomplete even long after germanium intake was stopped. The total dose of ingested germanium (as dioxide, carboxyethyl germanium sesquioxide, germanium-lactate-citrate, or unspecified forms) varied from 15 to over 300 g; the exposure duration varied from 2 to 36 months. In laboratory animals, elevated germanium in tissues and impaired kidney and liver function were observed in a life-time drinking water (5 ppm germanium) study. Other toxicities associated with ingested germanium products in human cases were also demonstrated in animal studies with germanium dioxide and sometimes other germanium compounds. Based on the evidence of persistent renal toxicity associated with germanium dioxide, the lack of conclusive findings of differential nephrotoxicity of organic germanium compounds, and the possibility of contamination of the organic germanium products with inorganic germanium, it is clear that germanium products present a potential human health hazard.

Insulin-like growth factor-1 receptor (IGF-1R) regulates carcinogenesis and tumor development and is expressed in normal endometrium. Vascular endothelial growth factor C (VEGF-C) promotes lymph node metastasis. We investigated IGF-1R, VEGF-C and D2-40 in endometrial adenocarcinoma and the association between IGF-1R and lymphatic metastasis, using an immunohistochemical S-P method with 40 cases of endometrial adenocarcinoma and 14 of normal endometrium. IGF-1R expression differed significantly between normal endometrium and adenocarcinoma; it was associated with histological grade but not surgical stage. IGF-1R overexpression was associated with metastasis, but expression was not. VEGF-C expression was greater in normal endometrium than in adenocarcinoma and was associated with metastasis but not with surgical stage or histological grade. IGF-IR and VEGF-C expression were correlated in endometrial adenocarcinoma, and lymphatic vessel density was closely related to both. Abnormal IGF-IR and VEGF-C expression may be important in lymph node metastasis of endometrial adenocarcinoma and might be used to evaluate the prognosis.

Currently, praziquantel is virtually the only drug used for the treatment of human schistosomiases (WHO, 2002). Although there is little direct evidence of the existence of praziquantel resistance in field isolates of schistosomes, decreased sensitivity to the drug has been reported in some Schistosoma species from several endemic areas (Tchuem–Tchuente et al., 2001; Alonso et al., 2006; Melman et al., 2009). The screening and development of novel antischistosomal drugs, as alternatives to praziquantel, therefore need to be given high priority. One derivative of artemisinin, dihydroartemisinin, shows activity against many parasites and, when administered orally to mammals, is rapidly absorbed, widely distributed and promptly excreted and metabolised (Tu, 2009). Single oral doses of dihydroartemisinin have recently been found effective against the 7-day-old schistosomula and 35-day-old adult worms of Schistosoma japonicum (Li et al., 2011). The aim of the present study was to explore the effects of multiple doses of dihydroartemisinin and of combined treatments with dihydroartemisinin and praziquantel against S. japonicum in experimentally infected mice, mainly to see if such treatments led to increased efficacy.

Praziquantel (PZQ) is now widely used for the treatment of human schistosomiasis. However, in recent years, there has been a growing concern about the resistance of Schistosoma to PZQ. The mechanisms of PZQ action against Schistosoma and resistance of Schistosoma to PZQ are poorly understood. Here, we report differential susceptibilities to PZQ between male and female cercariae in the PZQ-susceptible and PZQ-resistant isolates of Schistosoma mansoni, using tail loss as a measurement of PZQ action. The miracidia were collected by hatching eggs collected from faeces of infected mice. Single-sex cercaria lines were made by infecting a single Biomphalaria glabrata snail with a single miracidium. The sex of each single-sex cercaria line was identified by a direct W1-specific polymerase chain reaction (PCR) technique. Single-sex cercariae of two isolates were exposed to four different concentrations of PZQ, respectively. The tail shedding of cercariae was observed under a dissecting microscope for five time points up to 100 min after adding PZQ. The results showed that male cercariae have higher tail-shedding rates than that of female cercariae when PZQ-susceptible isolates of S. mansoni are exposed to the same concentration of PZQ. But this phenomenon was not observed in the PZQ-resistant isolates. This sexual differential resistance phenomenon of S. mansoni suggests that resistance to PZQ is induced by decreasing the PZQ susceptibility of male worms. The experiment described here may also be useful for developing tests to detect PZQ resistance in the field.

A 53-years-old woman was admitted to our hospital because of pleural effusion. She underwent pleural biopsy and diagnosed as mesothelioma. Right extrapleuralpneumonectomy was performed. We counted asbestos bodies in the resected lung. 443,571 asbestos bodies were counted in 1 gram of dry lung. We thought that she was heavily exposed to asbestos. Since high risk of incidence of mesothelioma is suggested among her fellow worker, special investigation is necessary for asbestos exposure.

We planned an intervention study to investigate the late outcome of limited surgery for cStage IA lung cancer by several video-assisted thoracic surgery (VATS) procedures.VATS partial resection was done for non-solid tumors less than 1.5 cm in maximum diameter with non-solid component on high resolution computed tomography (HRCT) [group A]. VATS segmentectomy with minor thoracotomy with ND1 + alpha lymph node dissection was done for tumors less than 2.0 cm in maximum diameter that was not included in the group A (group B). Tumors of less than 3.0 cm in diameter that did not fit into the other 2 groups were treated by VATS lobectomy with minor thoracotomy plus ND2 lymph node dissection (group C).A total of 159 patients were enrolled during the 5-year enrollment period (group A: 21 patients, group B: 43 patients, group C: 95 patients). The recurrence-free 5-year survival rate was 100% in the group A, 82.8% in the group B, and 78.4% in the group C, showing no significant differences between the groups. Twenty-eight % of patients was switched to surgical techniques involving more extensive resection in the group A and B. while 6% of the patients was switched to thoracotomy overall. The overall recurrence rate was 10.7% (n=17), while the locoregional and distant recurrence rate was 5.7% (n=9) and 5.0% (n=8), respectively.This controlled intervention study suggested that limited surgery by VATS approaches for cStage IA lung cancer are acceptable as cancer operation.

The present study investigates the effects of Ni{sup 2+} and other components of nickel electroplating water on the survival and reproductive capacity of the cladoceran Moina macrocopa, a common inhabitant of small ponds and rice paddies in Hong Kong and Southern China.

The aim of this study was to assess if the entire mediastinum (M), the bilateral supraclavicular area (S), and the left gastric area (L) should be all included in the irradiation volume. The clinical data of 204 patients with thoracic esophageal squamous cell carcinoma who had undergone prophylactic postoperative radiotherapy after radical surgery were retrospectively reviewed. They were classified into four groups: group A, 26 patients with irradiated M alone; group B, 139 patients with irradiated M + S; group C, 10 patients with irradiated M + L; and group D, 29 patients with irradiated M + S + L. The 5-year disease-free survival rates were 36% in group A, 31% in group B, 40% in group C and 44% in group D (chi2=3.05, P =0.39), respectively. Multivariate analysis revealed that the irradiated extent was not a significant influential factor (hazard ratio=0.84, 95% confidence interval, 0.69-1.03, P =0.10). None of 43 patients without the L irradiated and with disease in the upper and middle upper thirds (defined in middle third but with upper third invaded), and one of 83 patients without the L irradiated and with disease in the middle third only thoracic esophagus were shown to have abdominal lymph node metastasis. Supraclavicular lymph node metastasis in patients in the lower and middle lower thirds (defined in middle third but with lower third invaded) were, respectively, 1/43 and 1/18 whether the S was irradiated or not. It seems unnecessary that the L be irradiated when the primary site is in the upper, middle, and middle upper thirds of the thoracic esophagus after radical surgery. Similarly, S may be unnecessarily irradiated in the lower and middle lower thirds.

Patients with Peutz-Jeghers syndrome (PJS) are known to be at risk of gastric cancer (GC), and the STK11 gene is a susceptibility gene for PJS. However, as no cases of PJS with GC in which a STK11 germline mutation has been identified have ever been reported and other susceptibility genes have also been suggested to be involved in PJS, the relation between STK11 germline mutations and GC in PJS is still unknown. In this study, we used sequencing analysis to investigate the STK11, CDH1, and TP53 loci for a germline mutation in two siblings with PJS with primary GC. A novel type of the STK11 germline mutation, c.890delG, encoding a truncated protein (p.Arg297fsX38) was identified, but no germline mutations of the CDH1 and TP53 genes were detected. No inactivation of the wild-type allele by somatic mutation or chromosomal deletion or hypermethylation at the 5'-CpG site of STK11 was detected in the GC. This is the first report of a STK11 germline mutation in a PJS patient with GC and should contribute to establishing correlations between the STK11 germline mutations and GC in PJS patients.

A reversed-phase high performance liquid chromatographic method was established for determination of intestinal trefoil factor (ITF) in burned rats. The analysis was carried out on a Hypersil C4 column (30 nm, 5 microns, 4.6 mm i.d. x 250 mm) with gradient elution of acetonitrile-trifluoroacetic acid-water solution at a flow rate of 1 mL/min and detected by a UV detector at 214 nm. The volume proportion of trifluoroacetic acid in water is 0.1% and the volume proportion of acetonitrile in mobile phase ranged from 19.5% to 42.0%. The linear range of the method was 1 mg/L-100 mg/L with relative coefficient of 0.9989. The minimum detection limit was 0.5 mg/L. The recovery of ITF added ranged between 93.95% and 105.90%. The intra-day and inter-day RSD of ITF were less than 5.33% and 6.10% respectively. This method is precise, accurate and can be used for the determination of ITF in intestinal mucosal of burned rats. Therefore, it is helpful in the research of comparing the effects of enteral feeding and parenteral nutrition on ITF expression.

To study the expression and significance of transforming growth factor-beta 1(TGF-beta 1) in nasal polyps.Expression of TGF-beta 1 in nasal polyps from 34 patients and middle turbinates from 30 patients with deviation of nasal septum were prospectively studied with immunohistochemistry. Each tissue section was observed under optical microscope.1. The TGF-beta 1 positivity in extracellular matrix and in cells in the stroma was significantly higher in nasal polyps than in middle turbinates (P0.01). 2. The distribution and shape of TGF-beta 1 expressing cells in nasal polyps was similar to that of eosinophil, their positivities were significantly correlative (P0.05). 3. The positivity of TGF-beta 1 did not correlate with clinical type of nasal polyps (P0.05), eosinophil infiltration correlated significantly with clinical type of nasal polyps(P0.05).1. The TGF-beta 1 may contribute to some of the pathologic changes observed in nasal polyps, such as thickening of the epithelial basement membrane and stromal fibrosis. 2. Eosinophils in nasal polyps represent a major source of TGF-beta 1. 3. Eosinophils infiltration may play a prominent role in the development and recurrence of nasal polyps.

To investigate approaches of diagnosis and therapy to hemangioma of external ear and improve the effects of diagnosis and therapy.Eight cases of hemangioma of external ear were analyzed retrospectively. All patients were unilateral hemangioma. 5 were performed digital subtraction angiography (DSA) before operation, of which 3 were performed embolization simultaneously. 7 were operated, 1 was not done. Racemose hemangioma was 5 and cavernous hemangioma was 2 according to pathologic diagnosis.All patients have followed up 1 to 5 years, 5 were healed, 2 were controlled, and 1 was not treated.Surgery was effective approach to hemangioma of adults. It suggested that it was the key of controlling bleeding during operation that DSA and embolization before operation or ligating artery of blood supply during operation.

To study the relations of chemotherapy-induced tumor necrosis to plasma concentration of platin and primary tumor temperature in hyperthermic isolation limb perfusion (HILP) with cisplatin, and to investigate the correlation between the tumor necrosis rate and the relapse-free survival (RFS).Fifteen patients with II B osteosarcoma in the lower extremities were treated with neoadjuvant chemotherapy. Among them, 10 were male and 5 female. The average age was 18 years (ranging from 13 to 29). Chemotherapy included a single bonus dose of HILP with cisplatin (CDDP, 15 mg/m(2)). The plasma concentration of platin and the tumor temperature in the affected limb were measured during the course of the HILP with CDDP. Limb salvage surgery was performed in 9 patients and amputation in 6. After surgery, serial sections of the excised tumor specimens were made to determine the tumor necrosis rate. All of the patients were followed up for more than 5 years.The highest attained tumor temperature was between 41.4 degrees C - 43.0 degrees C (mean 42.3 degrees C +/- 0.46 degrees C), and the platin concentration ranged from 4.56 microg/mL to 14.66 microg/mL (mean 8.93 microg/mL +/- 3.16 microg/mL) during the course of HILP with CDDP. Thirteen patients with a necrosis rate of over 90% were well responded, and the remaining two with a necrosis rate 87.2% and 86.3% were poor responded. Eight patients remained tumor-free for 5 years. Primary tumor temperature and platin concentration were significantly related to the tumor necrosis rate (P = 0.001 and P0.001, respectively). No significant correlation was noted between the long-term survival rate and the three parameters in the regression analysis.HILP with CDDP is useful in the treatment of primary osteosarcoma. Increased tumor necrosis ensure a successful surgical excision of tumor. HILP however is still limited to the patients who are not candidates for lime salvage surgery, because the same condition of high temperature and high concentration of platin are not applicable to distant metastasis.

To determine whether tumor angiogenesis correlates with progression of gastric carcinoma.Microvessel counts (MVC) of 131 specimens resected from patients with gastric carcinoma were investigated by immunohistological staining with a monoclonal antibody against F-VIII RAg, counting the mean number of microvessels in the five areas of highest vascular density under 200 times magnification microscopy. Correlation among MVC, various clinicopathologic factors, and prognosis was studied.MVC increased with TNM stage, the MVC of patients with advanced stage disease was significantly higher than that of early stage patients (P0.01). MVC was significantly higher in tumors with deep penetration (P0.05), lymph node metastasis (P0.001) and distant metastasis (P0.05) than in those without invasion and such metastasis. The recurrence rate after curative resection in hypervascular group (MVCor 16) was 58.4%, which was significantly higher (P0.05) than that in the hypovascular group (MVC16). Moreover, the prognosis of patients with a high MVC was significantly poorer than that of those with a low MVC. The probability of 5 year survival rate was estimated by P = e(1.6231-0.1036 x MVC)/1 + e(1.6231-0.1036 x MVC). Multivariate analysis indicated that MVC is an independent prognostic factor in gastric cancer.Angiogenesis within gastric cancer is an indicator of tumor behavior and may identify patients at higher risk for recurrence and poorer prognosis.

The idiotypic determinant (Id) of the immunoglobulin expressed by a B-cell malignancy can serve as an effective tumor-specific antigen but is only weakly immunogenic. This study demonstrates that the immunogenicity of the tumor Id protein can be dramatically increased by directing it to antigen-presenting cells (APCs). Cytotoxic T-lymphocyte antigen 4 (CTLA-4) present on activated T cells has a strong binding affinity to both B7-1 and B7-2 molecules, which are primarily expressed on APCs. After construction of a fusion protein consisting of Id and CTLA-4 (Id-CTLA4), mice immunized with the fusion protein induced high titers of Id-specific antibody and T-cell proliferative responses without adjuvants and were protected from lethal tumor challenge. The Id-CTLA4 fusion protein was so potent that even low doses (down to 0.1 microg) of the immunogen were able to elicit strong antibody responses. By using an Id-CTLA4 mutant protein, the ability to bind B7 molecules on APCs was shown to be required for the enhanced immunogenicity of Id-CTLA4. These findings demonstrate that fusing CTLA-4 to a potential tumor antigen represents an effective approach to prime antitumor immunities in vivo and may be applicable to the design of vaccines for a variety of other diseases. (Blood. 2000;96:3663-3670)

A liposome containing diverse synthetic lipid derivatives of polyethylene glycol (PEG) results in smaller distribution volume and longer circulation time in blood and, thus, may improve drug targeting. The characteristics and therapeutic efficacy of immunoliposomes with similar liposomal formulation have never been studied in lymphoma models. We have developed immunoliposomes conjugated with S5A8 monoclonal antibody, an anti-idiotype antibody to 38C13 murine B-cell lymphoma, and loaded them with doxorubicin using an ammonium sulfate gradient. Purified antibodies were covalently coupled to the termini of PEG on the surface of small unilamellar liposomes. Cell binding and internalization ability of these immunoliposomes were estimated by a fluorescence assay using a pH-sensitive fluorescent dye (HPTS). The in vitro cytotoxicity of doxorubicin encapsulated in immunoliposomes was greater for idiotype-positive 38C13 cells than for the idiotype-negative variant of this cell line. In syngeneic C3H/HeN mice, doxorubicin encapsulated in immunoliposomes exhibited a long circulation time and was more effective at prolonging survival of mice bearing 38C13 tumor than non-targeted liposomal doxorubicin or free doxorubicin plus empty immunoliposomes. Our results demonstrate the superiority of targeted therapy with these immunoliposomes and its potential in lymphoma treatment.

A 15-year-old female was admitted because of the superior mediastinum mass on chest X-rays and sensory loss of ulnar side of the left arm. Computed tomographic scanning and magnetic resonance imaging revealed that the tumor was dumbbell-shaped and invaded the vertebral canal through the intervertebral foramen between C 7 and Th 1. At first laminectomy of vertebrae (C 6-Th 1) was made in a prone position and intra-spinal portion of the tumor was resected. Then the patient was placed in a supine position and the chest was opened by left hemicollar incision and sternotomy to the 2nd intercostal space. The tumor was divided into two parts at the level of 1st rib and completely removed. The pathological diagnosis was schwannoma. This procedure is safe and useful for dumbbell type tumor located in superior mediastinum, especially in case of large tumor from neck to the thoracic cavity.

Anti-idiotype (Id) antibodies (Abs) have been shown to be effective in treatment of B-cell lymphoma in animal models and in clinical trials. The combination of interleukin-2 (IL-2) can augment the therapeutic effect of anti-Id Abs. To further improve the power of the combined therapy, a monoclonal anti-Id Ab, S5A8, specifically recognizing a murine B-cell lymphoma 38C13, was genetically modified to contain the IL-2 domain and thus use the unique targeting ability of Abs to direct IL-2 to the tumor site. Two forms of the anti-Id-IL-2 fusion proteins were constructed: one configuration consisting of mouse-human chimeric IgG (chS5A8-IL-2) and the other containing only the variable light (VL) and variable heavy (VH) Ab domains covalently connected by a peptide linker (scFvS5A8-IL-2). Both forms of the anti-Id-IL-2 fusion proteins retained IL-2 biological activities and were equivalent in potentiating tumor cell lysis in vitro. In contrast, the antigen-binding ability of scFvS5A8-IL-2 was 30- to 40-fold lower than that of the bivalent chS5A8-IL-2. Pharmacokinetic analysis showed that scFvS5A8-IL-2 was eliminated about 20 times faster than chS5A8-IL-2. Finally, it was shown that chS5A8-IL-2 was very proficient in inhibiting 38C13 tumor growth in vivo, more effectively than a combined therapy with anti-Id Abs and IL-2, whereas scFvS5A8-IL-2 did not show any therapeutic effect. These results demonstrate that the anti-Id-IL-2 fusion protein represents a potent reagent for treatment for B-cell lymphoma and that the intact IgG fusion protein is far more effective than its single-chain counterpart.

In this study, we provide direct evidence that the magnitude and nature of the immune response to a DNA vaccine can be differentially regulated by codelivery of various mouse cytokine genes. Mice immunized with a hepatitis B virus (HBV) DNA vaccine and the IL-12 or IFN-gamma gene exhibited a significant enhancement of Th1 cells and increased production of anti-HBV surface IgG2a Ab, as well as a marked inhibition of Th2 cells and decreased production of IgG1 Ab. In contrast, coinjection of the IL-4 gene significantly enhanced the development of specific Th2 cells and increased production of IgG1 Ab, whereas Th1 differentiation and IgG2a production were suppressed. Coinjection of the IL-2 or the granulocyte-macrophage-CSF gene enhanced the development of Th1 cells, while the development of Th2 cells was not affected, and the production of IgG1 and IgG2a Ab were both increased. The CTL activity induced by HBV DNA vaccination was most significantly enhanced by codelivery of the IL-12 or IFN-gamma gene, followed by the IL-2 or granulocyte-macrophage-CSF gene, whereas codelivery of the IL-4 gene suppressed the activity. When challenged with HBV surface Ag (HBsAg)-expressing syngeneic tumors, significant reduction of tumor growth was observed in mice that were coadministered the IL-12 gene but not the IL-4 gene. Taken together, these results demonstrate that application of a cytokine gene in a DNA vaccine formulation can influence the differentiation of Th cells as well as the nature of an immune response and may thus provide a strategy to improve its prophylactic and therapeutic efficacy.

Four biomaterials including pork fat (PF), glutaradehyde crosslinked pork peritonium (GCP), glutaradehyde cross-linked human amnion (GCA) and freeze-dried human amnion (FDA) dura were compared for their ability to prevent the dura from adhesion in 24 dogs. Noncontiguous laminectomies were performed on each dog. Laminectomized areas where the above mentioned 4 materials put randomly were served as experimental groups while laminectomized areas with autologous fat transplants put in place were served as standard control and empty control was set with the area left untreated. The formation of fibrosis and the adhesion of the dura were evaluated at 1, 2, 3, 4, 6, 12 weeks after operation by using a double-blind protocol. Methods of observation included gross anatomical evaluation, histological evaluation, computer-assisted image analysis, fibroblasts counting and measurement of SCEP. The results showed: 1. The epidural scar arose from the raw surface of erector spinal muscles and the bony edges created by the procedure; 2. Putting a suitable obstructor between the dura and the erector spinae muscle would make dura be exempted from adhesion; 3. The interpositional membrane should be tucked in between the bony edges in close proximity to the bony surface without leaving any room; 4. GCA seems to be efficient in preventing dural adhesion and reducing the invasion of the scar tissue in the spinal canal.