[Pulmonary malignant perivascular epithelioid cell tumor mixed with lung adenocarcinoma components: a case report and literature review].

Objective: To analyze the pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of pulmonary malignant perivascular epithelioid cell tumor (PEComa) with adenocarcinoma. Methods: In August 2020, the Department of Pathology, Dongguan People's Hospital of Southern Medical University, diagnosed a case of pulmonary malignant PEComa mixed with adenocarcinoma. The clinical data, pathological diagnosis, treatment plan and prognosis of the patient were analyzed, and the literature was reviewed. Firstly, "malignant perivascular epithelioid cell tumor"+" Pulmonary "+"adenocarcinoma" was used to search CNKI and Wanfang Medical Database, but no relevant reports were found. Then, we changed the search term as "pulmonary malignant perivascular epithelioid cell tumor", and search for PubMed, Embase, Web of Science and Cochrane by combining the subject terms with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" as subtopics. The language was Chinese or English and the search deadline was November 2020. Results: The patient, a 46-year-old male, was admitted to the hospital on August 20, 2020, due to "repeated cough and chest pain for more than 10 days, accompanied by rapid weight loss". Serology detected increased expression of lung non-small cell lung cancer related antigens. PET-CT showed a large mass of soft tissue density in the left thoracic cavity with an SUV value of 22.8. The postoperative pathological diagnosis was malignant PEComa mixed with adenocarcinoma and the lymph nodes were metastasized. Due to the detection of EGFR sensitive mutation, postoperative chemotherapy and targeted therapy were administered, and the current state was stable. A total of 12 cases of pulmonary malignant PEComa were retrieved in the literature, which were common in middle-aged and elderly people. They usually presented with cough or chest tightness. Chest CT mostly showed round masses with clear boundaries, and 8 cases had metastasis to mediastinal lymph nodes and other organs. Conclusions: Pulmonary malignant PEComa is rare. It is the first report of the same mass with lung primary adenocarcinoma. The tumor progresses rapidly. Complete surgical resection of the lesion and lymph node dissection are more appropriate treatment strategies, supplemented by postoperative chemotherapy and targeted therapy. For cases diagnosed as pulmonary PEComa, long term follow-up should be performed, even if the pathological diagnosis is benign.

MiRNA-215-5p alleviates the metastasis of prostate cancer by targeting PGK1.

OBJECTIVE: MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which exert crucial functions in regulating biological progressions. Previous studies have demonstrated the anti-tumor effect of miRNA-215-5p. However, its specific role in influencing the progression of prostate cancer (PCa) remains unclear. This study aims to uncover the regulatory effect of miRNA-215-5p on the metastasis and prognosis of PCa. PATIENTS AND METHODS: MiRNA-215-5p levels in collected PCa tissues (n=52) and paracancerous tissues (n=52) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miRNA-215-5p level and pathological indexes, as well as overall survival of PCa patients, was analyzed. Regulatory effects of miRNA-215-5p on proliferative and metastatic capacities of LNCaP and DU-145 cells were evaluated through cell counting kit-8 (CCK-8) and transwell assay, respectively. Bioinformatics prediction was performed to search for the target genes of miRNA-215-5p and PGK1 was selected. The biological role of PGK1 in the progression of PCa was finally clarified by a series of rescue experiments. RESULTS: MiRNA-215-5p was lowly expressed in PCa tissues and cell lines. Low level of miRNA-215-5p predicted poor prognosis in PCa patients. The silence of miRNA-215-5p enhanced viability, migratory, and invasive capacities of LNCaP cells, while the overexpression of miRNA-215-5p yielded the opposite trends in DU-145 cells. PGK1 was predicted to be the target of miRNA-215-5p. PGK1 was upregulated in PCa tissues and cell lines and its high level predicted poor prognosis of PCa. Moreover, PGK1 level was negatively correlated to that of miRNA-215-5p in PCa tissues. PGK1 was able to reverse the regulatory effects of miRNA-215-5p on metastatic potentials of PCa cells. CONCLUSIONS: Downregulated miRNA-215-5p in PCa is closely related to distant metastasis and poor prognosis of affected patients. MiRNA-215-5p alleviates the malignant progression of PCa by targeting and downregulating PGK1.

Effect of miR-101 on proliferation and oxidative stress-induced apoptosis of breast cancer cells via Nrf2 signaling pathway.

OBJECTIVE: To explore the influence of micro ribonucleic acid (miR)-101 on breast cancer cell proliferation and apoptosis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway. MATERIALS AND METHODS: All MCF-7 cells were divided into 3 groups, namely control group, miR-101 mimic group (the cells were treated with 50 nmol/L miR-101 mimic), and miR-101 inhibitor group (the cells were treated with 50 nmol/L miR-101 inhibitor). The impact of miR-101 expression level on MCF-7 cell proliferation was evaluated via cell counting kit-8 (CCK-8) and colony formation assays. After the MCF-7 cells in the three groups were treated with 100 nM H2O2 for 12 h, the change in the apoptosis rate was detected via flow cytometry. Moreover, the influence of miR-101 expression level on the Nrf2 signaling pathway was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: According to the CCK-8 assay results, compared with that in control group, the proliferation rate of cells notably declined at 48, 72, and 96 h in miR-101 mimic group, and the difference was statistically significant (p<0.01), while it was substantially raised in miR-101 inhibitor group, showing a statistically significant difference (p<0.01). Compared that in control group, the cell colony formation rate was remarkably lowered in miR-101 mimic group, and the difference was statistically significant (p<0.01), while it was substantially raised in miR-101 inhibitor group (p<0.01). According to the flow cytometry assay results, compared with that in control group, the apoptosis of MCF-7 cells was markedly enhanced in miR-101 mimic group, showing a statistically significant difference (p<0.01), while it was weakened in miR-101 inhibitor group, with a statistically significant difference (p<0.01). The influence of miR-101 on the expression level of Nrf2 was detected via RT-PCR, and it was found that the messenger RNA (mRNA) expression level of Nrf2 was notably lower in miR-101 mimic group than that in control group (p<0.01), while it was raised in miR-101 inhibitor group. Western blotting results showed that compared with control group, miR-101 mimic group had a substantially lowered protein expression level of Nrf2 in the cell nucleus, with a statistically significant difference (p<0.01), while it was notably raised in miR-101 inhibitor group and the difference was statistically significant (p<0.01), indicating that miR-101 can remarkably lower the nucleoprotein expression level of Nrf2. CONCLUSIONS: The results of this study imply that miR-101 can inhibit the expression of Nrf2 to suppress the proliferation of breast cancer cells and enhance their sensitivity to oxidative stress, which provides a theoretical basis for reversal of tumor resistance.

High glucose promotes prostate cancer cells apoptosis via Nrf2/ARE signaling pathway.

OBJECTIVE: To explore the influences of high glucose on the proliferation and apoptosis of prostate cancer cells and analyze its possible mechanism of action. MATERIALS AND METHODS: Human prostate cancer cell line LNCaP was divided into control group, mannitol group, and high glucose group. Then, the proliferation in each group was detected via methyl-thiazolyl-tetrazolium (MTT) assay. Hoechst staining assay was performed to determine the apoptosis level in each group. Western blotting was employed to measure the expression levels of apoptosis-related proteins and nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and γ-glutamylcysteine synthetase (γ-GCS) proteins. The cellular reactive oxygen species (ROS) level was measured through 2,7-dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect the content of lactate dehydrogenase (LDH) and inflammatory factors. RESULTS: High glucose significantly promoted the proliferation of prostate cancer cells LNCaP (p<0.01) and increased the apoptosis level of cells (p<0.01). In high glucose group, the expression level of Caspase-3 protein was overtly increased (p<0.01), while that of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) was significantly decreased (p<0.01). High glucose group had clearly increased the content of ROS (p<0.01), LDH (p<0.01), and interleukin-6 (IL-6) (p<0.01), but decreased the content of IL-10 (p<0.01). High glucose notably lowered the protein expression levels of Nrf2, HO-1, and γ-GCS in the cells (p<0.01). CONCLUSIONS: High glucose represses the activation of the Nrf2/anti-oxidation response element (ARE) signaling pathway in prostate cancer cells and increases the content of ROS, IL-6, and the expression of apoptotic proteins in the cells, thus promoting the apoptosis of prostate cancer cells.

[Gender difference in clinical manifestations and comorbidities in the patients with spondyloarthritis].

Objectives: The aim of the study was to determine whether there was gender difference in clinical manifestations and comorbidities in the patients with Spondyloarthritis (SpA) in China. Methods: 346 patients fulfilling ASAS criteria for SpA were recruited from the Third Affiliated Hospital of Sun Yat-sen University, including 280 males and 66 females. A comparison was conducted in terms of age at onset, disease course, family history, HLA-B27 positivity, clinical manifestations, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), the bath ankylosing spondylitis disease activity index (BASDAI) and AS disease activity score (ASDAS), and comorbidities between male and female patients. Results: Compared with female patients, male patients were younger at disease onset (22±7 vs 27±9, P<0.001),had higher rates of morning stiffness (74.3%), and higher scores of CRP and ASDAS-CRP (P<0.010, P=0.014). However, no significant gender difference was observed in other clinical parameters like clinical manifestations, family history, HLA-B27 positivity, BASDAI, and BASFI and treatment. Male SpA patients had a higher prevalence of Hepatitis B virus (HBV) infection (26.2%) than that of female patients (8.3%), and a higher prevalence of osteoporosis (30.5% vs 14.3%,P<0.01), especially with a lower lumbar T score. Logistic regression analysis reviewed that limited weight (OR=0.94, P<0.001), high ASDAS-CRP (OR=1.58, P=0.006) and male (OR=8.02, P=0.004) are more inclined to have osteoporosis. Conclusion: Compared with female patients, male patients were younger at disease onset and higher scores of CRP and ASDAS-CRP. No significant gender difference was observed in clinical manifestations, family history, HLA-B27 positivity, BASDAI, and BASFI and treatment. Male SpA patients had a higher prevalence of HBV infection and osteoporosis than female patients. Comorbidities should be paid more attention in the patients with SpA.

[Analysis of distribution and drug resistance of pathogens isolated from 541 hospitalized children with burn infection].

Objective: To investigate the distribution and drug resistance of pathogens isolated from hospitalized children with burn infection. Methods: Totally 541 patients were hospitalized in Fujian Medical University Union Hospital, the 180th Hospital of Chinese People's Liberation Army(PLA), the 92th Hospital of PLA, and Longyan First Hospital from January 2013 to December 2015. Totally 848 clinical specimens (blood, catheter tip attachments, wound exudate, etc.) were collected for pathogen detection. After being identified by an automatic microbiological identification system, drug resistance of pathogens to 41 commonly-used antibiotics in clinic including gentamicin, aztreonam, erythromycin, clindamycin, etc. was tested by K-B paper disk diffusion method or minimal inhibitory concentration detection method. The SPSS 20.0 statistical software was used to analyze the following subjects: the detection rates of pathogens in different years, from different hospitals, and with different sources, the distribution of gram-negative bacteria, gram-positive bacteria, and fungi, the distribution of major pathogens, the detection rate of methicillin-resistant Staphylococcus, the resistant rates of common gram-positive bacteria and gram-negative bacteria to antibiotics. Results: The total detection rate of pathogens was 35.14% (298/848). The detection rates of pathogens were 52.29% (114/218), 33.20% (83/250), and 26.58% (101/380) in 2013, 2014, and 2015 respectively, 38.45% (198/515), 51.43% (18/35), 71.70% (38/53), and 17.96% (44/245) from Fujian Medical University Union Hospital, the 180th Hospital of PLA, the 92th Hospital of PLA, and Longyan First Hospital respectively, and 136/261, 8/137, 3/4, and 7/48 from wound exudate, blood, drainage fluid or tissue fluid, and the other specimens (including catheter tip attachments, sputum, feces) respectively. Among the 298 pathogens, 159 (53.36%) strains were gram-positive bacteria, 129 (43.29%) strains were gram-negative bacteria, and 10 (3.36%) strains were fungi. The detection rate of Staphylococcus aureus was the highest, totally 68 strains, accounting for 22.82%, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus epidermidis, with 37, 31, and 22 strains, accounting for 12.42%, 10.40%, and 7.38% respectively. Among Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) accounted for 70.59% (48/68). Among Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis (MRSE) accounted for 68.18% (15/22). The resistant rates of MRSA and MRSE to penicillin and ampicillin were all 100.0%, and the resistant rates of MRSA to erythromycin, tetracycline, clindamycin and those of MRSE to erythromycin, cotrimoxazole were high. The high resistant rate of Pseudomonas aeruginosa towards antibiotics was detected with cotrimoxazole (83.3%) only. The resistant rates of Acinetobacter baumannii towards piperacillin, ceftazidime, and cotrimoxazole were high (from 58.8% to 71.4%). Conclusions: During the three years, there is large difference in the detection rate of pathogens from these four hospitals in Fujian province. The majority of pathogens were Gram-positive bacteria. The four dominant pathogens were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus epidermidis. Most of the pathogens were resistant to antibiotics commonly used in clinic in different degree, especially MRSA, MRSE and Acinetobacter baumannii, which showed high resistance towards antibiotics.

Comparative proteomics analysis of human osteosarcomas and benign tumor of bone.

We conducted comparative proteomic analysis of osteosarcoma, with hopes of identifying the specific protein markers of osteosarcoma and improve the understanding of tumorigenesis and progression of osteosarcoma. Proteins extracted from osteosarcoma tissue and benign bone tumors, including osteoblastoma, chondroblastoma, and giant cell tumor of bone, were examined using two-dimensional gel electrophoresis followed by mass spectrometry analysis and database searches. We also validated the expression levels of interesting proteins by Western blotting assay and immunohistochemical staining. Intensity alterations of 30 spots were detected in osteosarcoma, and 18 of these spots were finally identified, including 12 up-regulated proteins and 6 down-regulated ones. The up-regulated proteins include VIM, TUBA1C, ZNF133, EZR, ACTG1, TF, and so on. The six down-regulated proteins include ADCY1, ATP5B, TUBB, RCN3, ACTB, and YWHAZ. Subsequent immunohistochemical staining and Western blotting assay for TUBA1C and ZNF133 in osteosarcoma samples confirmed the observation obtained by proteomic analysis. Our results suggest that these identified proteins may be potential biomarkers for osteosarcoma tumorigenesis and therapeutics. Aberrant expression of cytoskeletal- and microtubule-associated proteins in osteosarcoma may provide an advantage for tumor invasion and metastasis by affecting the stability of microtubule, which consequently influences the prognosis of patients.

Histamine excites rat cerebellar Purkinje cells via H2 receptors in vitro.

Recent neuroanatomical studies have revealed a direct hypothalamocerebellar histaminergic pathway. However, the functional significance of the histaminergic fibers in the cerebellum is not yet clear. In this study, the effects of histamine on the firing of cerebellar Purkinje cells (PCs) were investigated in vitro. Histamine predominantly produced excitatory (106/111, 95.5%) and in a few cases inhibitory (5/111, 4.5%) responses in PCs. The histamine-induced excitation was not blocked by perfusing the slice with low Ca2+ high/Mg2+ medium (n = 8), supporting a direct postsynaptic action of histamine. The histamine H2 receptor antagonist ranitidine effectively blocked the excitatory response of PCs to histamine (n = 20), but triprolidine, an H1 receptor antagonist, could not significantly block the histamine-induced excitation, or only very slightly decreased the excitatory effect of histamine on the cells (n = 13). On the other hand, the highly selective H2 receptor agonist dimaprit mimicked the excitatory effect of histamine on PCs and this dimaprit-induced excitation was also blocked by ranitidine (n = 20), but not triprolidine (n = 8). However, the H1 receptor agonists betahistine and 2-thiazolylethylamine did not show any effect on the PCs (n = 9 and 14). These results reveal that histamine excites cerebellar PCs via H2 receptors and suggest that the hypothalamocerebellar histaminergic fibers may play an important role in functional activities of the cerebellum.

[The excitatory effects of histamine on cerebellar cortical Purkinje cells in the rat].

The effects of histamine on Purkinje cells (PCs) in lobule X of cerebellar cortex were investigated in rat cerebellar slices. Histamine elicited PCs' responses predominately excitatory (94.4%, 51/54), only few inhibitory (5.6%, 3/54). The excitatory response could not be abolished by perfusing the slices with low Ca2+/high Mg2+ medium. The excitatory response of PCs to histamine could be blocked by histamine H2 receptor antagonist ranitidine, but not by H1 receptor antagonist triprolidine readily. These results suggest that histamine exerts an excitatory effect on the PCs via H2 receptors. Presumably, hypothalamo-cerebellar histaminergic fibers participate in the regulation of somatic and non-somatic functions of the cerebellum.

[A tentative discussion on problems of enhancement of population quality in China].

PIP: Population quality is an undeniable fact. It means people's scientific and cultural literacy, their ability to work, and their physical health condition. Population quality is influenced by sociological and physiological factors. Population quality improves as society and production power improve. Industrialization and rapid development in science and technology in western countries required workers with higher levels of education and physical concentration. In order to change the poor economic situation and achieve the "Four Modernizations" in China, a great number of people possessing knowledge of modern science and technology to manage modern production is needed. Agricultural and meat production need to be improved, thereby improving the people's physical health condition. The importance of population quantity control must be realized. In order to lower the population growth rate we can increase the economic development and improve people's educational level and physical health. To improve population quality we should continue nationwide family planning programs, change our educational structure (increase vocational training and utilize the electronic media and correspondence courses), improve the physical health of children and youth, expand our social welfare system, and emphasize research on genetics and eugenics.^ieng