[The effect of captopril and losartan on paraquat-induced pulmonary fibrosis and PlGF expression in the lungs of rats].

Objective: To investigate the dynamic expression of placenta growth factor (PlGF) in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT (1) -receptor blocker losartan on paraquat-induced pulmonary fibrosis. Methods: 84 adult healthy female Sprague-Dawley (SD) rats were randomly divided into four groups of different treatments designated as: Control, PQ alone (PQ) , captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril (60 mg/kg; ig) or Losartan (10 mg/kg; ig) once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A semiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PlGF. Results: Inflammatory cell infiltration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group (P<0.05) . On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group (P<0.05) . The hydroxyproline contents in the intervention groups were significantly decreased as compared with model group (P<0.01) . PlGF mRNA on day 7, 14, 28 (1.28±0.29vs0.10±0.01、0.80±0.07vs0.10±0.01、0.65±0.13vs0.10±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF mRNA on day 7, 14, 28 in the captopril and Losartan intervention groups were significantly decreased (0.94±0.04、0.71±0.09、0.52±0.24 and 0.80±0.12、0.66±0.11、0.51±0.03) . PlGF positive expression index on day 7, 14, 28 (2.27±0.34 vs0.13±0.01、1.78±0.41 vs0.14±0.03、1.25±0.69 vs0.13±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF positive expression index on day 7, 14, 28 in the captopril and Losartan treatment groups were significantly decreased (1.53±0.78、1.17±0.79、0.97±0.61 and 1.36±0.63、1.24±0.80、0.83±0.47) . PlGF positive expression index on day 7 in the two intervention groups were significantly decreased, as compared with PQ group (P<0.05) . Conclusion: PlGF may plays an important role in the development of pulmonary fibrosis following paraquat-induced lung injury in rats. Captopril and losartan had an inhibitory effect on paraquat-induced pulmonary fibrosis, and the effect may be due to inhibition of angiotensin II and, in part, be associated with reduction in PlGF.

The role of dexmedetomidine in immune tissue and inflammatory diseases: a narrative review.

OBJECTIVE: Adrenergic receptors belong to the G protein-coupled receptor family and are one of the important targets of modern drug therapy. Dexmedetomidine (DEX) is a highly selective agonist of alpha2 receptor, a member of the adrenergic receptor family, which are widely found in immune tissues and which mediate the biological behaviour of the inflammatory immune system. This review mainly summarizes the role of DEX in immune tissue and inflammation-related diseases, to provide a theoretical basis for clinical treatment. MATERIALS AND METHODS: We searched the PUBMED, EMBASE, and Cochrane libraries separately to obtain published literature on DEX related to immune tissue and inflammatory diseases. The mesh (dexmedetomidine replaces DEX, microglia, astrocytes, spleen, marrow, lymph nodes) and their corresponding keywords used for the searches, and no time limit for retrieval. The latest search was conducted on July 1, 2022. RESULTS: By reading a lot of relevant literature, we found that DEX reduces the inflammatory response of brain tissue by interfering with microglia and astrocytes. DEX can regulate the expression of CD40 and CD86 markers on the surface of splenocytes and reduce the secretion of inflammatory cytokines by splenocytes. In addition, we found that DEX reduced inflammation-related diseases such as neuroinflammation, myocarditis, liver cirrhosis, osteoarthritis, upper respiratory tract infection, pancreatitis, spinal tuberculosis, pulpitis, colon inflammation and rheumatoid arthritis, and improved prognosis. CONCLUSIONS: DEX has anti-inflammatory and improved prognosis in many inflammatory related diseases and is expected to become a targeted drug for the treatment of inflammatory diseases.

Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports.

BACKGROUND: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. METHODS: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. RESULTS: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ(2) = 2.12, P = 0.5473). CONCLUSIONS: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.

Survival outcome of weak estrogen/progesterone receptor expression in HER2 negative breast cancer is similar to triple negative breast cancer.

BACKGROUND: Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy. METHODS: Medical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups. RESULTS: Regarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.

Nucleostemin stabilizes ARF by inhibiting the ubiquitin ligase ULF.

Upregulated expression of nucleolar GTPase nucleostemin (NS) has been associated with increased cellular proliferation potential and tumor malignancy during cancer development. Recent reports attribute the growth regulatory effects of NS protein to its role in facilitating ribosome production. However, the oncogenic potential of NS remains unclear, as imbalanced levels of NS have been reported to exert growth inhibitory effect by modulating p53 tumor-suppressor activity. It also remains in questions if aberrant NS levels might have a p53-independent role in regulation of cell proliferation and growth. In this study, we performed affinity purification and mass spectrometry analysis to explore protein-protein interactions influencing NS growth regulatory properties independently of p53 tumor suppressor. We identified the alternative reading frame (ARF) protein as a key protein associating with NS and further verified the interaction through in vitro and in vivo assays. We demonstrated that NS is able to regulate cell cycle progression by regulating the stability of the ARF tumor suppressor. Furthermore, overexpression of NS suppressed ARF polyubiquitination by its E3 ligase Ubiquitin Ligase for ARF and elongated its half-life, whereas knockdown of NS led to the decrease of ARF levels. Also, we found that NS can enhance NPM stabilization of ARF. Thus, we propose that in the absence of p53, ARF can be stabilized by NS and nucleophosmin to serve as an alternative tumor-suppressor surveillance, preventing potential cellular transformation resulting from the growth-inducing effects of NS overexpression.

Enhancement of proliferation and differentiation of erythroid progenitors by co-transduction of erythropoietin receptor and H-ras cDNAS into single CD34(3+) cord blood cells.

Our previous studies have demonstrated that retrovirus-mediated gene transduction of either the human erythropoietin receptor (EpoR) or H-ras cDNA into single purified hematopoietic progenitor (HPC), CD34(3+), cells from cord blood (CB) resulted in increased numbers and sizes of erythroid cell containing colonies. We therefore evaluated if there were further effects when H-ras and EpoR genes were co-transduced into the same progenitor cells. Highly purified single sorted CD34(3+) CB cells were transduced with retroviral vectors encoding EpoR or H-ras cDNA. At the single cell level, and in response to stimulation by a combination of growth factors, including Epo, the number of colonies formed by BFU-E and CFU-GEMM was significantly increased in cells transduced with either single H-ras or EpoR cDNA compared to mock virus-transduced cells as previously described. Increased numbers of BFU-E, but not CFU-GEMM, colonies were produced from cells simultaneously co-transduced with both EpoR and Hras genes. Little or no growth was seen in transduced cells without exogenously added cytokines. The size of all types of colonies including CFU-GM was increased in cells transduced with H-ras and/or EpoR cDNAs, and the greatest increase was noticed in cells co-transduced with both genes. Integration and expression of either gene in individual colonies as assessed by PCR and RT-PCR analysis were 45-62% and 48-58%, respectively, with approximately 31% of the cells containing and expressing both genes. These results add to information suggesting an enhancing interacting role of H-ras and EpoR in erythroid proliferation/differentiation.

Steroid-induced tumor lysis syndrome in a patient with preleukemia.

Tumor lysis syndrome (TLS) is a well recognized complication of chemotherapy and radiotherapy for leukemia, lymphoma as well as rapidly growing malignancies. Less described is the occurrence of TLS following steroid therapy alone. Herein, we report on a 32-year-old male with myelodysplastic syndrome, characterized by refractory anemia with excess blasts in transformation, who developed acute oliguric renal failure 12 hours after methylprednisolone 1.0 g for presumed autoimmune thrombocytopenia. Laboratory investigations revealed typical findings of TLS, including hyperkalemia, marked hyperuricemia, hyperphosphotemia, hypocalcemia and urine uric acid to creatinine ratio 1.8 (> 1.0). Long hemodialysis (8 hours) was initiated for 3 consecutive sessions. Renal function recovered 1 week later. This case high-lights that single-dose steroid administration in a patient with hematological malignancy may cause the potential life-threatening complications of TLS. Prophylactic management prior to the use of steroid therapy for a variety of purposes is absolutely required in high-risk patients.

Electronic monitoring of fetal heart rate and determination of fetal scalp blood pH in prediction of intrapartum fetal distress.

A prospective study on consecutive fetal monitoring in 559 deliveries was carried out. The difference between the first 30-minute and the last 30-minute monitoring was compared. Abnormal fetal heart rate (FHR) pattern in the last 30 minutes combined with abnormal fetal scalp blood pH has a good predictability of 1- and 5-minute Apgar scores. The correlation of fetal heart rate-uterine contraction (FHR-UC) monitoring (525 cases) and fetal scalp blood pH determinations (FSB-pH) (79 cases) with the fetal condition was assessed. It is indicated that the first 30-minute FHR tracing can reflect the fetal status in labor, and FHR-UC monitoring assessment is evidently superior to FSB-pH in the prediction of a vigorous fetus. Whereas, FSB-pH is superior to FHR-UC monitoring in the prediction of a compromised fetus.

Aortic dissection presenting as fever of unknown origin.

Acute aortic dissection may have variable presentations, making the diagnosis clinically challenging. Although fever is a common accompanying feature, it rarely dominates the clinical setting. We report the case of a patient who sustained a prolonged spiking fever with unknown origin following acute aortic dissection. The case serves as a reminder that prolonged fever may be the principal residual sequelae after acute aortic dissection or one of the protean clinical manifestations of painless aortic dissection.

[The value of saturated phosphatidylcholine determination in amniotic fluid of pregnancies in the third trimester].

The quantity of saturated phosphatidylcholine (SPC) in amniotic fluid was measured in 50 cases of normal late pregnancy and 21 women in labor, by improved Tsai's method. Normal values of SPC in different gestational weeks were obtained. The results showed that SPC in the amniotic fluid increased with the advancing gestational weeks and more significantly after the onset of labor. This study indicated that SPC determination can predict fetal lung maturity with high specificity, sensitivity and accuracy.

[The dynamic measurements of human body's unbalance].

A through study of the postural stability of 40 subjects has been conducted with a stabilometer and the computer system. The subjects stand on the testing platform for 10 seconds and meanwhile the sum of frequency spectrum is being analyzed. The most men subjects maintain a little sway well within timits during the trials. The testing conditions include open eyes, close eyes, 10 degrees, 20 degrees, 30 degrees of platform inclination, transverse vision tracking, longitudinal vision tracking and vectorial vision tracking, All testing results show that there are unbalance differences between different age groups under different conditions.

Testicular plasmacytoma with bone dissemination without medullary plasmacytosis.

A 34-year-old man was diagnosed as having solitary testicular plasmacytoma. He had received palliative radiotherapy, several combined chemotherapies including CHOP chemotherapy (vincristine, cyclophosphamide, Adriamycin, and prednisone), MP (melphalan and prednisone) and M-2 protocol (melphalan, prednisone, vincristine, carmustine, and cyclophosphamide), and interferon therapy as 3 million units subcutaneous injection three times a week for 1 year. Extensive bone plasmacytoma developed 7 years later without bone marrow involvement. We suggest that early use of combined chemoradiotherapy and high-dose chemotherapy with autologous stem cell support should be investigated in patients with testicular plasmacytoma with dissemination.

Suppurative salmonella thyroiditis in a patient with chronic lymphocytic leukemia.

We describe an 82-year-old man with undiagnosed chronic lymphocytic leukemia (CLL) who presented with acute swelling of the thyroid goiter. Subsequent thyroid aspirate and blood culture yielded group B Salmonella thyroid abscess with septicemia. Infectious complications are the major cause of morbidity and mortality in patients with CLL since most of them can be timely detected and few can arise from innocent-looking lesions.

Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia.

We recently treated a patient with severe aplastic anaemia (SAA) who also had chronic hepatitis B virus (HBV) infection. The HBV serological status at the time of diagnosis of SAA was HBsAg(+) and HBeAg(+). Subsequent analysis of the precore region of HBV DNA showed wild-type. He received anti-thymocyte globulin (ATG) and cyclosporin A (CsA) therapy twice. After each course of ATG infusion and during CsA therapy he developed lymphopenia for 1 and 2.5 months, respectively. His serum alanine aminotransferase (ALT) became normalized during the period of lymphopenia, but the serum HBV viral load increased. When his peripheral lymphocytes count recovered, his ALT became elevated again. Lamivudine was effective to normalize his elevated ALT and suppress viral replication. The phenomenon observed in this case supports the prevailing notion that hepatitis B flare-up in HBV carriers after chemotherapy is caused by an immune-mediated mechanism. Meanwhile, this is the first documented case of SAA who developed HBV reactivation upon recovery of lymphopenia after immunosuppressive therapy. This also highlights the necessity of pre-emptive therapy with lamivudine in SAA/HBsAg(+) patients to receive immunosuppressive therapy with ATG/CsA.

Stenotrophomonas maltophilia septicemia with pyomyositis in a chemotherapy-treated patient.

Pyomyositis is a rare complication of chemotherapy. A 35-year-old male patient with myelodysplastic syndrome developed Stenotrophomonas maltophilia bacteremia shortly after chemotherapy, and Stenotrophomonas maltophilia-related pyomyositis was encountered after recovery from neutropenia. He recovered completely after surgical drainage and a protracted course of antibiotic treatment. It is postulated that subclinical myopathy, immunosuppression secondary to the malignancy, or chemotherapeutic drugs may predispose to pyomyositis. Early recognition of this unusual complication in a cancer patient undergoing chemotherapy can prevent further catastrophes.

Trousseau's syndrome related to adenocarcinoma of the colon and cholangiocarcinoma.

Malignancy-related thromboembolism, so-called Trousseau's syndrome, can present as acute cerebral infarction, non-bacterial thrombotic endocarditis (NBTE) and migratory thrombophlebitis. It is usually attributed to a cancer-related hypercoagulable state, chronic disseminated intravascular coagulopathy (DIC), or tumour embolism. We report on two patients with adenocarcinoma of the colon and cholangiocarcinoma who developed widespread thromboembolism during disease progression. Both did poorly despite aggressive institution of anticoagulation therapy. These cases emphasize that cerebral infarction or refractory thromboembolism in cancer-treated patients should prompt investigation for recurrent or metastatic disease or progression of the underlying malignancy. Optimal treatment remains to be established.

Enhancing effects of co-transduction of both human erythropoietin receptor and c-kit cDNAs into hematopoietic stem/progenitor cells from cord blood on proliferation and differentiation of erythroid progenitors.

Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34+ and CD34 cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34+ or CD34 cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was more apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in cells transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34+CD71+ cells in expanded cells from single CD34 cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells.