FRZB: a potential prognostic marker for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.

Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1).@*METHODS@#Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay.@*RESULTS@#The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) μg/ml, which was significantly lower than (0.301±0.04) μg/ml of CA46-C23-KNC cells and (0.338±0.05) μg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle.@*CONCLUSION@#The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Research progress in Persicae Semen / 中草药

The aim of this review is to summarize the advances in studies on Persicae Semen, a Chinese herbal medicine, in the fields of nature and flavor, preparation, quality control, chemical composition, pharmacology, and toxicology. Persicae Semen and its extracts present various pharmacological activities, such as cardiovascular protection, neuroprotection, immunoregulation, antitumor effects and hepatic and renal protection. Though amygdalin, one of the main components in Persicae Semen, had been well studied, the activities and mechanisms of other potential active ingredients should also be more concerned.

Effect of ulinastatin on liver function of patients after bilateral total knee arthroplasty / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of ulinastatin, a urinary trypsin inhibitor, on the postoperative liver function in patients who have received bilateral total knee arthroplasty (TKA) under pneumatic tourniquet.</p><p><b>METHODS</b>Totally 40 patients who were scheduled to receive bilateral TKA under thigh tourniquet were randomly assigned into trial group (U group, receiving intravenous ulinastatin) and control group (C group, receiving natural saline). All patients received the same general anesthesia and postoperative analgesia. The plasma concentrations of alanine transaminase (ALT), total bilirubin (TBil), and direct bilirubin (DBil) were recorded and compared preoperatively and 4, 24, 48, and 72 hours after the surgery.</p><p><b>RESULTS</b>The demographic data were not significantly different between these two groups (P>0.05). The ALT was not significantly changed after the surgery in the C group (P>0.05) but was significantly decreased 48 hours (P=0.002) and 72 hours (P=0.001) after the surgery in the U group. TBil and DBil were significantly increased 48 hours (P=0.012, P=0.000) and 72 hours (P=0.000, P=0.000) after the surgery in C group, while only that at 48 hours (P=0.010, P=0.038) was significantly increased in the U group. ALT 4 hours (P=0.026), 48 hours (P=0.013), 72 hours (P=0.004) after the surgery were significantly lower in the U group than those in C group. TBil at the 72 hours postoperatively in U group was significantly lower than that in C group (P=0.036). DBil was not significantly different between C group and U group at all time points (all P>0.05).</p><p><b>CONCLUSION</b>The application of ulinastatin in bilateral TKA can protect postoperative liver function.</p>

Cytotoxic activity of spleen lymphocytes in BALB/c mice immunized by HSP110-HER2/neu ICD / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the cytotoxic responses of spleen T lymphocytes (CTL) in BALB/c mice induced by recombinant HSP110-HER2/neu ICD complex.</p><p><b>METHODS</b>Tumor-bearing mouse model was immunized by HSP110-HER2/neu ICD complex. The IFN-γ level secreted by activated spleen T lymphocytes was detected by enzyme linked immunospot assay (ELISPOT). The corresponding CTL activity was measured by granzyme release assay.</p><p><b>RESULTS</b>The BALB/c mouse model of human mammary tumor highly expressing HER2/neu was established. HSP110-HER2/neu ICD complex immunization led to a significantly higher level of INF-γ than that in HSP110-P(789-797) immunized and HER2/neu ICD immunized mice. HSP110-HER2/neu ICD complex immunized animals also show significant CTL activity. The results of immunohistochemical staining showed that the number of blue spots in the PBS group was 4.57 ± 1.33, HSP110 group 6.83 ± 2.08, HER2/neu ICD group 16.17 ± 2.86, HSP110-P(789-797) group 43.67 ± 4.78, and SP110-HER2/neu ICD group 76.51 ± 8.17. The number of IFN-γ-secreting spleen lymphocytes in the HSP110-HER2/neu ICD group was significantly higher than that in the HSP110-P(789-797) group, and that of HSP110-P(789-797) group was significantly higher than that of HER2/neu ICD group (P < 0.01). The target cell-killing rate of the PBS group was (8.15 ± 1.27)%, HSP110 group (9.51 ± 1.51)%, HER2/neu ICD group (14.03 ± 2.45)%, HSP110-P(789-797) group (25.99 ± 3.04)% and HSP110-HER2/neu ICD group (38.15 ± 3.95)% (all P < 0.01).</p><p><b>CONCLUSIONS</b>HSP110-HER2/neu ICD complex can promote the proliferation and maturation of T lymphocytes into CTLs, and might be used as anti-tumor vaccine to induce potent cytotoxic T lymophocyte immunoresponse against specific tumor cells.</p>

Insights into restrictive cardiomyopathy from clinical and animal studies / 老年心脏病学杂志（英文版）

Catdiomyopathies are diseases that primarily affect the myocardium,leading to serious cardiac dysfimction and heart failure.Out of the three major categories of candiomyopathies(hypertrophic,dilated and restrictive),restrictive cardiomyopathy(RCM)is less common and also the least studied However,the prognosis for RCM is poor as some patients dying in their childhood The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective.In this article,we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models.This will help for a better understanding of tare mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.

Detection of core antigen of hepatitis virus C in patients infected with hepatitis virus C and B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the effect of hepatitis virus B on the detection rate of core antigen of hepatitis virus C in sera of chronic hepatitis C patients.</p><p><b>METHOD</b>HCVcAg and HCV RNA in sera were detected in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV. At the same time, HBV DNA and HBeAg in sera were detected in 62 patients infected with HCV and HBV. Then we analyzed the correlation between HCVcAg and HBeAg/HBV DNA. The detection rates of HCVcAg in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV were 72.7% (64/88) and 38.7% (24/62), respectively (x2 = 17.358, P less than 0.01).</p><p><b>RESULTS</b>The detection rates of HCV RNA in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV was 81.8% (72/88) and 53.2% (33/62)respectively (x2=20.110, P less than 0.01). In 62 patients infected with HCV and HBV, the detection rate of HCVcAg in HBeAg positive patients and HBeAg negative patients were 28.6% (12/42) and 60% (12/20), respectively (x2 = 7.547, P = 0.011). Moreover, the positive rates of HBV DNA in HBeAg positive patients and HBeAg negative patients were 42.9% (18/42) and 80% (16/20), respectively (P more than 0.05). The detection rates of HCVcAg in HBV DNA positive patients and HBV DNA negative patients were 39.1% (18/46) and 37.5% (6/16), respectively (x2 = 0.013, P = 0.908). Compared with the detection rates of HCVcAg in patients only infected with HCV, the detection rate of HCVcAg in HBeAg or HBV DNA negative patients infected with HCV and HBV were 60% (12/20) (x2 = 1.266, P = 0.261) and 37.5% (6/16) (x2 =7.635, P less than 0.01), respectively.</p><p><b>CONCLUSION</b>The detection rate of HCVcAg in patients infected with HCV and HBV is relatively low. The reason is possibly that HBeAg inhibits duplication of HCV and decreases the expression of HCVcAg.</p>

Application of lumber plexus blockade for hip fracture repair in elderly patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the lumber plexus blockade as anesthesia technique for hip fracture repair in elderly patients.</p><p><b>METHODS</b>We retrospectively analyzed the peri-operative data of 87 hip fracture patients, aged 70 years or older, who underwent surgical repair at our hospital between 2003 and 2006. Patients were divided into three groups according the anesthesia techniques applied: general anesthesia (GA) group (n=21), epidural anesthesia (EA) group (n=37), and lumber plexus blockade (LPB) group (n=29).</p><p><b>RESULTS</b>The peri-operative data were comparable among three groups, except that intra-operative the dosage of fentanyl was significantly lower in LPB group compared with in GA group(P0.05), and the blood urea nitrogen 1 day after surgery was significantly increased in GA group(P0.05).</p><p><b>CONCLUSION</b>Lumber plexus blockade combined with small-dose intravenous anesthesia is an optional anesthetic technique for elderly patients undergoing hip fracture repair.</p>

Comparison of the influences of continuous femoral nerve block and patient controlled intravenous analgesia on total knee arthroplasty / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the influences of continuous femoral nerve block (CFNB) and patient-controlled intravenous analgesia (PCIA) on postoperative pain scores,knee rehabilitation,and stress response after total knee arthroplasty (TKA).</p><p><b>METHODS</b>Totally 32 adult patients scheduled for elective total knee arthroplasty were equally randomized into CFNB group or PCIA group. Intraoperative hemodynamics and fentanyl dose were recorded. Pain was assessed at rest and during continuous passive motion (CPM) using a visual analog scale at post-anesthesia care unit (PACU) and 4, 8, 12, 24, and 48 hours postoperatively. Morphine consumption was also recorded. As indicators of stress and inflammatory response,the leukocyte count, serum lactic acid, blood glucose, serum C-reactive protein (CRP), and serum cortisol were determined on admission, to operation room, immediately after skin incision, before extubation,on post-operation day 1 (POD1), and on POD2.</p><p><b>RESULTS</b>CFNB group showed significantly lower heart rate compared with PCIA group 60 minutes and 90 minutes intraoperatively (Pü0.05). Intraoperative consumption of fentanyl was significantly lower in CFNB group (137.5∓44.4) μg than in PCIA group (264.1∓67.1) μg (Pü0.01). The CFNB group showed significantly lower VAS scores both at rest and during CPM compared with PCIA group at all time points (Pü0.05). Morphine consumption was significantly lower in CFNB group than in PCIA group at different time points (Pü0.05 or Pü0.01). The maximal continuous passive motion amplitude of CFNB group were significantly larger than that of PCIA group on POD1 [(55.0∓9.4) vs.(44.6∓9.9), P[(76.3∓11.0) vs. (67.5∓10.3), P<0.05]. The incidences of somnolence and nausea/vomiting in CFNB group were 37.5% and 37.5%, respectively,which were significantly lower than those of PCIA group (75.0% and 81.3%) (Pü0.05). Patient satisfaction scores on anesthesia and post-operative analgesia was significantly higher in CFNB group than in PCIA group (93.1∓7.9 vs. 79.1∓11.9, respectively) (Pü0.05).</p><p><b>CONCLUSION</b>After TKA,CFNB technique provides more stable intraoperative hemodynamics than PCIA, with better pain relief,faster postoperative knee rehabilitation,less side effects,and higher patient satisfaction.</p>

Application of caffeine-halothane contracture test in the diagnosis of malignant hyperthermia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the application of caffeine-halothane contracture test (CHCT) in the confirmation of malignant hyperthermia (MH).</p><p><b>METHODS</b>One patient who underwent radical gastrectomy presented with clinical manifestations of MH during routine intravenous-inhalation anesthesia process. Isoflurane inhalation and the operation were ceased immediately and emergency management approaches such as physical cooling therapy were taken. Meanwhile, the levels of serum creatine kinase (CK), serum myoglobin, and urinary myoglobin were examined and rectus abdominis was taken and then CHCT was performed to confirm the clinical diagnosis. Total genome was extracted from the patient and then exons 2-18, 39-46, and 90-104 of ryanodine receptor 1 (RYR1) gene were screened to detect mutations using DNA sequencing technique.</p><p><b>RESULTS</b>The patient was diagnosed as MH episode by clinical characteristics and postoperatively continuous elevation of the levels of CK, serum myoglobin, and urinary myoglobin (30 times higher than normal level). Despite halothane test was negative, the diagnosis of MH was verified by the positive result of caffeine test. DNA sequencing of RYR1 gene of the patient revealed c. 6724C > T (p. T 2 206M).</p><p><b>CONCLUSION</b>CHCT can be used to confirm the diagnosis of MH.</p>