Analysis of reproductive damage in earthworms (Amynthas corticis) exposed to cypermethrin.

Cypermethrin contamination was a potential threat to soil organisms. In the present work, reproductive damage in earthworms (Amynthas corticis) exposed to cypermethrin was investigated. It was found that earthworms could absorb and accumulate residual cypermethrin in soil, and also earthworm activities helped accelerate the degradation of cypermethrin in soil. The accumulation of cypermethrin in earthworms induced sperm damage, and cypermethrin not only caused the imbalance of calcium homeostasis in earthworm sperm cells by inhibiting earthworm sperm Ca2+-ATP and Ca2+-Mg2+-ATP enzyme activities but also caused barriers in acrosome reaction. It also affected sperm energy supply of earthworms by inhibiting the activity of Na+-K+-ATPase and Mg2+-ATPase of earthworm sperm. Meanwhile, the inhibition of acrosome enzyme activity of earthworm sperm by cypermethrin led to hinder fertilization and reduced cocoon production of earthworms, and the damage of cypermethrin to sperm of earthworm was a significant cause of its reproductive toxicity. The results of the evaluation of IBR index showed that reproductive toxicity of cypermethrin to earthworms reduced with the increasing time. The decreased reproductive toxicity of cypermethrin to earthworms at the later stage of exposure (42-56 d) might be due to a combination of reduced absorption of cypermethrin in soil by earthworms, decreased accumulation of cypermethrin in the body, and improved sperm capacitation.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

[The clinicopathologic features and differential diagnosis of ocular Kimura disease and epithelioid hemangioma].

Objective: To investigate the clinicopathologic features and differential diagnosis of ocular Kimura disease (KD) and epithelioid hemangioma. Methods: It was a retrospective case series study. The data of 10 patients with ocular KD and 3 patients with ocular epithelioid hemangioma from the Pathology Department of Eye & ENT Hospital of Fudan University from January 2010 to December 2019 were retrospectively analyzed, including clinical manifestations, morphology and immunophenotypes. Results: Among patients with ocular KD, there were 9 males and 1 female with an age from 7 to 75 years (mean, 30 years). There were 6 unilateral cases and 4 bilateral cases. The disease mainly involved the orbit in 3 patients, the lacrimal gland in 5 patients and the eyelid in 2 patients. The ophthalmic presentation included a palpable periorbital or eyelid mass with eyelid swelling and ptosis, proptosis and displacement of the eyeball, and ocular dysmotility. Three patients had a history of lymphadenopathy. The disease course ranged from 6 months to 7 years (mean, 34 months). All the patients had elevated peripheral blood eosinophilia. Three patients of ocular epithelioid hemangioma were all males with age from 25 to 60 years old. They were all unilateral cases with 1 right eye and 2 left eyes. The disease respectively involved eyelid and orbit, the eyebrow skin and the inner canthus skin. They presented with eyelid swelling, orbital mass or subcutaneous nodule for 5 months to 2 years. All patients (11 eyes) with KD underwent incisional or excisional biopsy. The histopathology revealed follicular hyperplasia of lymphoid tissue with active germinal centers in orbital fibroadipose tissue. There were massive interfollicular eosinophils with eosinophilic microabscesses. Some swelling endothelial cells of proliferating vessels were seen. All the 3 patients (3 eyes) with ocular epithelioid hemangioma underwent excision of the lesions. Histopathological examination showed proliferation of small and medium blood vessels. The vessels were lined by endothelial cells with abundant eosinophilic cytoplasm which protruded into the lumen. The endothelial cells were positive for CD31, factor Ⅷ-related antigen and E26 transformation-specific related gene immunohistochemically. There was a moderate amount of lymphocytes, plasma cells and eosinophils surrounding blood vessels without eosinophilic microabscess. Conclusions: Both ocular KD and epithelioid hemangioma are more commonly seen in males and share the common histopathological features of vascular proliferation, swelling endothelial cells and eosinophilic infiltration. KD is an allergic benign lymphoid tissue proliferation characteristic of massive eosinophilic infiltration, whereas epithelioid hemangioma is a benign neoplasm of blood vessels with plump and epithelioid endothelial cells. (Chin J Ophthalmol, 2021, 57: 689-695).

[Intraocular perivascular epithelioid cell tumor: report of two cases].

Two male patients presented with painless vision loss to blindness in one eye, and the radiography examinations revealed an intraocular mass suspicious for choroidal melanoma. They underwent enucleation. The histopathological and immunohistochemical findings were compatible with the diagnosis of intraocular perivascular epithelioid cell tumor. Because of its rarity, intraocular perivascular epithelioid cell tumor is easy to be confused with other intraocular tumors on histopathological and immunohistochemical examinations. (Chin J Ophthalmol, 2021, 57: 857-860).

Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages.

BACKGROUND: Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum. OBJECTIVE: To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. METHODS: The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum-treated macrophages were investigated through experiments using human monocytic cell line (THP-1)-derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage-treponeme mixtures. RESULTS: Activation of autophagy and phagocytosis in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The percentage of spirochete-positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1. Inoculation of macrophage-treponeme mixtures into rabbits showed a 3.00-day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ2  = 5.406, P = 0.020] in the control compared with the si-Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin-1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group (P < 0.001)] and reduced the percentage of spirochete-positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). CONCLUSION: Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro. These data may be useful for understanding the host-pathogen relationship and establish the groundwork for strategies to combat syphilis.

[SMARCA4-deficient primary thoracic sarcoma:a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological characteristics of SMARCA4- deficient thoracic sarcomas. Methods: The clinical features and CT scans of SMARCA4-deficient thoracic sarcomas (n=5) diagnosed at Fudan University Cancer Hospital from December 2016 to October 2018 were reviewed. Hematoxylin-eosin staining, immunohistochemistry and targeted next generation sequencing were performed in available cases along with a literature review. Results: All 5 patients were males with age ranging from 32 to 65 years (average 54 years; median 61 years). Four patients were smokers except one with unknown smoking history. The average maximum diameter of tumor was 5.6 cm. Tumor primary sites included thoracic wall,thoracic cavity,lung and mediastinum. Histologically,tumor cells formed solid sheets or anastomosing islands with brisk mitotic figures accompanying with large areas of necrosis. Three cases focally exhibited rhabdoid morphology and vesicular chromatin. Immunohistochemically, SMARCA4, SMARCA2 and Claudin-4 were negative in all cases and all tumors demonstrated SOX2 and SMARCB1 nuclear positive staining. Among 3 cases analyzed by targeted next generation sequencing, concurrent SMARCA4 and p53 mutation was detected in all three cases. Mutations of STK11, ERBB4, NF2, GNAS, MTOR,MET and FGFR1 amplification were also detected among the three cases. The follow-up information was available in all 5 cases. Two patients died of the tumor. One relapsed multiple times after surgeries but was alive with disease. Two patients received radical excisions without relapse. Conclusions: SMARCA4-deficient thoracic sarcoma is a rare but highly-aggressive tumor with dismal prognosis. The tumor is featured by rhabdoid morphology histologically and distinctive immunohistochemical and molecular phenotype.

[Ocular natural killer/T cell lymphoma: a clinicopathologic analysis].

Objective: To evaluate the clinicopathological features of ocular natural killer(NK)/T cell lymphoma. Methods: Data of 21 patients (22 eyes) with ocular NK/T cell lymphoma treated at Eye & ENT Hospital of Fudan University from January 2006 to March 2018 were retrospectively analyzed for clinical data, morphology, immunophenotype and outcomes. Results: There were 10 males and 11 females with ages from 3 to 77 years (mean, 43 years). There were 20 unilateral cases (10 left eyes and 10 right eyes) and 1 bilateral case. Except for 1 case of corneal perforation resulting from the involvement of the conjunctiva and cornea, the other cases all involved the orbit (including eyelids and conjunctiva) as demonstrated by radiologic studies, with the lacrimal sac involved in 3 cases, and the nasal cavity or maxillary sinus involved in 2 cases. Three patients had been previously diagnosed sinonasal NK/T cell lymphoma with radiotherapy and chemotherapy. Two patients had a history of ovarian NK/T cell lymphoma with chemotherapy. One patient had multiple ulcers of skin and mucosa at presentation. There were 13 primary ocular NK/T cell lymphomas without evidence of nasal or systemic involvement. All patients presented with eyelid swelling and decreased visual acuity. There were proptosis in 18 cases, motility restriction in 13 cases, eyelid ulceration in 3 cases, and fever in 4 cases. They had all been previously diagnosed as orbital pseudotumor or cellulitis and there was no response to steroids and antibiotics. Pathological examination showed atypical lymphoid infiltration with an angioinvasive growth pattern causing coagulative necrosis. Cytologically, the medium-sized neoplastic cells showed irregular folded nuclei. The neoplastic cells were positive for cytoplasmic CD3ε, CD56, and cytotoxic molecules and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization. Seven patients were lost to follow-up. Ten patients died 2.0 to 17.0 months after diagnosis (mean, 6.3 months) despite treatment with chemotherapy and radiotherapy. Conclusions: Ocular NK/T cell lymphoma is a rare form of ocular lymphoma. There are primary NK/T cell lymphoma and secondary ocular NK/T cell lymphoma with nasal or systemic involvement. The rarity of this tumor and inflammatory signs make it challenging to identify these tumors early. The neoplastic cells are positive for cytoplasmic CD3ε, CD56, cytotoxic molecules and EBER in situ hybridization. Despite aggressive therapy, it demonstrates high lethality with poor prognosis. (Chin J Ophthalmol, 2019, 55: 374-380).

Factors associated with syphilis infection: a comprehensive analysis based on a case-control study.

This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17,304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048-1·785], current smoking (aOR 1·607, 95% CI 1·177-2·195), elevated BUN (aOR 1·782, 95% CI 1·188-2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.

Effects of Lysiphlebia japonica (Ashmead) on cotton-melon aphid Aphis gossypii Glover lipid synthesis.

The cotton-melon aphid, Aphis gossypii Glover, is a major insect pest worldwide. The wasp Lysiphlebia japonica (Ashmead) is the predominant parasitoid of cotton-melon aphids in north China. Parasitization has been reported to affect host lipids in several systems, but the lipid synthesis-related genes and transcription changes in the cotton-melon aphid-parasitoid interaction are not clear. In this study, 36 lipid synthesis-related genes were cloned and their transcription changes in parasitized aphids were studied by quantitative real-time PCR. In parasitized cotton-melon aphids, almost all key genes in the glycerolipid synthesis pathway were up-regulated, the rate-limiting enzyme diacylglycerol o-acyltransferase by 3.24-fold. The rate-limiting enzyme of the glycolytic pathway, pyruvate kinase, and the pace-making enzyme in citrate synthesis were 1.69-fold and 1.75-fold less in parasitized aphids than in unparasitized aphids, respectively. These results suggest increased glycerolipid synthesis in parasitized aphids but that citrate production from sucrose was decreased. Aconitate hydratase (aco), in the pathway that converts amino acids into citrate, was up-regulated. The number of fragments per kilobase per million mapped reads of the mitochondrial aco2 gene was only 4.6, whereas that of the cytoplasmic aco1 was 41.5, indicating that the citrate comes from amino acids in the cytoplasm of parasitized cotton-melon aphids.

Efficacy and safety of PI3K/Akt/mTOR inhibitors combined with trastuzumab therapy for HER2-positive breast cancer: a meta-analysis.

OBJECTIVE: Activation of the PI3K/AKT/mTOR pathway in patients with HER2-positive breast cancer is associated with acquired resistance to trastuzumab. This randomized controlled trial (RCTs) meta-analysis was designed to evaluate the clinical efficacy and safety of PI3K/Akt/mTOR inhibitors in combination with trastuzumab in HER2-positive breast cancer. MATERIALS AND METHODS: We searched on Web of Knowledge, PubMed, Embase, Cochrane, CNKI, and ClinicalTrials.Gov for RCTs comparing PI3K/Akt/mTOR inhibitors plus trastuzumab vs. standard trastuzumab treatments. Pooled estimates of progression-free survival (PFS), pathologic complete response (pCR), and incidence of adverse events were determined. RESULTS: 5 studies out of 610 were found to be eligible and were included in our analysis (n=1,548 participants). PI3K/Akt/mTOR inhibitors combination with trastuzumab treatments resulted in a statistically significant increase in PFS compared with conventional trastuzumab therapy (HR 0.82; 95% CI: 0.76-0.90; p<0.00001). The new combination treatment was more effective on hormone receptor-negative patients (HR 0.73; 95% CI: 0.58-0.93; p=0.010). In addition, the combination of PI3K/Akt/mTOR inhibitors with trastuzumab slightly increased the risk of some adverse events, such as neutropenia, leukopenia, fatigue, and anemia. CONCLUSIONS: The combination treatments of PI3K/Akt/mTOR inhibitors and trastuzumab for PI3K/Akt/mTOR inhibitors combined with trastuzumab treatments for patients with HER2-positive breast cancer can improve median progression-free survival while increasing the incidence of adverse events. It is still controversial based on the current evidence. Due to the limited number and quality of included studies, more high-quality studies are needed for further analysis.

[Independent and combined effects of pre-pregnancy BMI and gestational diabetes on early adiposity rebound timing in children].

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.

Long non-coding RNA UCA1 promotes the progression of paclitaxel resistance in ovarian cancer by regulating the miR-654-5p/SIK2 axis.

OBJECTIVE: Ovarian cancer (OC) is a common tumor in women, and the development of chemoresistance is the major obstacle to its treatment. Long non-coding RNAs (LncRNAs) have been linked to chemoresistance in many cancers. However, the function of lncRNA urothelial carcinoma associated1 (UCA1) in paclitaxel (PTX) resistance of OC is not well elucidated. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UCA1, microRNA-654-5p (miR-654-5p) and salt inducible kinase 2 (SIK2). Cell PTX resistance and proliferation were evaluated by 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The abilities of apoptosis, migration and invasion were measured by Flow cytometry and Transwell assays, respectively. Dual-luciferase reporter assay was used to verify the interaction among UCA1, miR-654-5p and SIK2. Besides, Western blot analysis was performed to assess the protein level of SIK2. RESULTS: UCA1 was markedly upregulated in OC tissues and PTX-resistant OC cells. Silencing of UCA1 restrained the PTX resistance, reduced the proliferation, migration, invasion and enhanced the apoptosis of PTX-resistant OC cells. MiR-654-5p could be sponged by UCA1, and the inhibitory effect of its overexpression on the progression of PTX-resistant OC cells could be reversed by overexpressed-UCA1. Moreover, SIK2 was a target of miR-654-5p. Silencing of SIK2 could hinder the PTX resistance and suppress the progression of PTX-resistant OC cells, while miR-654-5p inhibitor could invert this inhibitory effect. Also, the expression of SIK2 was regulated by miR-654-5p and UCA1 expression. CONCLUSIONS: LncRNA UCA1 plays an active role in PTX resistance of OC and is crucial to maintain the development of PTX resistance in OC, which provides a new therapeutic target for the study of OC chemoresistance.

Are nontreponemal tests suitable for monitoring syphilis treatment efficacy? Evidence from rabbit infection models.

OBJECTIVES: We aimed to characterize kinetics of non-treponamal antibody titres during the natural course of syphilis and explore their roles in monitoring syphilis treatment efficacy. METHODS: Sixty New Zealand white male rabbits were challenged with Nichols or Amoy Treponema pallidum strains, and the rapid plasma reagin (RPR) test was performed to quantify non-treponemal antibody titres during the infection course. Viable T. pallidum in the challenged rabbits was assessed with rabbit infectivity tests. RESULTS: The RPR titres of the Nichols or Amoy strain between no benzathine penicillin G (BPG) and BPG treatment subgroups displayed a similar trend: first ascending and then descending. Compared with baseline, the proportions of fourfold decline in RPR titres in the Nichols or Amoy group presented a similar result on days 30, 60 and 180 between the no BPG and BPG treatment subgroups (0%, 0/5; 80%, 4/5; 100%, 5/5; vs. 0%, 0/5; 80%, 4/5; 100%, 5/5; p 0.999; 0%, 0/5; 80%, 4/5; 80%, 4/5; vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.098, respectively). Compared with the maximum baseline titre, the proportion of fourfold decline in PRR titre also showed a similar result in the two groups on days 30, 60 and 180 between the no BPG and the BPG treatment subgroups (0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.129; 0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 80%, 4/5; 100%, 5/5; 100%, 5/5; p 0.091, respectively. Moreover, regardless of whether the RPR titres presented a fourfold decline, viable T. pallidum could be detected in untreated rabbits' lymph nodes at 30, 60 and 180 days post infection, while viable T. pallidum was not detected in any of the treated rabbits' lymph nodes. CONCLUSIONS: The RPR titre increased and then decreased (even became negative) during the natural course of syphilis, similar to that seen after BPG treatment. The RPR tetre is thus a questionable indicator of syphilis treatment efficacy.

Effect and mechanism analysis of siRNA in inhibiting VEGF and its anti-angiogenesis effects in human osteosarcoma bearing rats.

OBJECTIVE: To explore the effect of siRNA in inhibiting vascular endothelial growth factor (VEGF) expression in tumor cells from human osteosarcoma bearing rats and its anti-angiogenesis effect, to further study the reliability, effectiveness and safety of VEGF as a therapeutic target in treating osteosarcoma. MATERIALS AND METHODS: After treatment, the long diameter and short diameter of tumor lesion were detected by Vernier caliper, and the tumor volume and tumor inhibition rate were calculated. The whole-body fluorescence imaging was used to detect the general morphology and volume change of tumor lesion before and after treatment. The rats were killed after treatment, RT-PCR and Western blot were used to detect VEGF expression. MTT was used to detect the proliferative ability of tumor cells in vitro. RESULTS: Three chemotherapies could inhibit the growth of tumor lesion, the decrease of tumor volume was significant (p < 0.05), the therapeutic effect in Ad-VEGF-siRNA + neoadjuvant chemotherapy group was better than the other two groups, the differences were statistically significant (p < 0.05). Furthermore, the three chemotherapies could inhibit the invasiveness of tumor cells, which was most significant in Ad-VEGF-siRNA + neoadjuvant chemotherapy group (p < 0.05). CONCLUSIONS: The growth of tumor tissue in osteosarcoma bearing rats is inhibited in Ad-VEGF-siRNA group, Ad-VEGF-siRNA + neoadjuvant chemotherapy group and Ad-VEGF-siRNA + anti-angiogenesis chemotherapy group. The effect in Ad-VEGF-siRNA + neoadjuvant chemotherapy is more significant than simple biological therapy or Ad-VEGF-siRNA + anti-angiogenesis chemotherapy.

Increased expression and nuclear accumulation of basic fibroblast growth factor in primary cultured astrocytes following ischemic-like insults.

Basic fibroblast growth factor (bFGF) is a biological active polypeptide with potent trophic effects on neurons, glia and endothelial cells. In the present study, we examined the temporal expression profile of bFGF protein in cultured cortical astrocytes under ischemic-like conditions such as serum-free, glucose-free or glutamate application. A peak increase of bFGF level was observed at 24 h after the initiation of insults. A striking increase in the bFGF immunoreactivity and a moderate increase in the fibroblast growth factor receptor-1 (FGFR-1) immunoreactivity were also found in the astrocytes treated with serum- or glucose-deprivation or glutamate. The increased bFGF immunoreactivity and FGFR-1 immunoreactivity were mainly accumulated in the nuclei of astrocytes. The results suggest that the expression of bFGF and FGFR-1 in the astrocytes, especially in the nuclear interior, can be up-regulated under ischemic-like conditions and that the up-regulation of bFGF and FGFR-1 may play an important role in the maintenance and repair of the central nervous system (CNS) after ischemia.

Roles of p53, c-Myc, Bcl-2, Bax and caspases in glutamate-induced neuronal apoptosis and the possible neuroprotective mechanism of basic fibroblast growth factor.

By using flow-cytometric analysis, we examined the involvement of p53, c-Myc, Bcl-2 and Bax in the glutamate-induced cell death in cultured cortical neurons. The activities of caspase-1-like and caspase-3-like proteases were also measured after the glutamate treatment. The apoptosis rate of the cells increased after 12 h and 24 h treatment with glutamate. The temporal profile of p53, c-Myc, Bcl-2, Bax expression and caspases activation after glutamate treatment suggest that Bcl-2, c-Myc and caspase-3 play important roles in the excitotoxic neuronal cell death. The down-regulation of Bcl-2 may be an important early stage event, which may cause the activation of caspase-3. c-Myc is also involved in the process of apoptosis though its precise role remains elusive. bFGF exhibited the capability to antagonize the neuronal apoptosis caused by glutamate. The antiapoptotic potential of bFGF may result from its attenuating effect on the down-regulation of Bcl-2 induced by glutamate and, subsequently, blockade of apoptosis cascade. This may provide a possible explanation for its neuroprotective effect against ischemic cell death.

Study of prognostic predictors for non-small cell lung cancer.

BACKGROUND: The outcome of treatment in non-small cell lung cancer (NSCLC) remains poor. One of the reasons is that in many patients its biological behavior does not follow a definite pattern, and can not be accurately predicted prior to treatment. In the present study we have examined the significant prognostic predictors. METHODS: One hundred and fifty-eight patients with NSCLC entered this study. They received surgery alone (95 cases) or combined therapy with postoperative irradiation (63 cases). Three types of data have been collected: (1) clinical characteristics: age, sex, Karnofsky performance status, weight loss, T stage, and N stage; (2) histopathology studies: histological types, tumor differentiation, status of vascular and lymphatic vessel invasions; (3) laboratory measurements by immunohistochemistry assay: oncoprotein overexpression, including pan-ras, c-myc, neu, epidermal growth factor receptor (EGFR) and p53, and tumor cell proliferation by proliferating cell nuclear antigen (PCNA). RESULTS: For the entire group, 5-year actuarial survival, local control and distant metastasis rates were 44, 63 and 40%, respectively. In the univariate analyses, T stage, N stage and lymphatic vessel invasion correlated to survival; T stage and N stage to local control; N stage, lymphatic vessel invasion and pan-ras protein positive stain to distant metastasis. When the index of oncoprotein positive stains was used, the higher index was associated with a higher distant metastasis rate. In the multivariate analyses, T stage, N stage and lymphatic vessel invasion could be independent predictors for survival; T stage for local control; N stage, lymphatic vessel invasion and index of positive oncoprotein stains for distant metastasis. CONCLUSIONS: Late T and N stages, lymphatic vessel invasion and multi-oncoprotein positive stains would predict poor prognoses for NSCLC.

Highly efficient ligands for palladium-catalyzed asymmetric alkylation of ketone enolates.

[figure: see text] Ferrocene-modified chiral pocket ligands have been studied in the palladium-catalyzed asymmetric alkylation of simple ketone enolates, in which (R,R,Sp,Sp)-1 containing two pairs of matched chiralities, central chirality and planar chirality, behaved very efficiently in this reaction and up to 95% ee value was achieved.