Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report / 中华医学杂志(英文版)

BACKGROUND@#Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).@*METHODS@#From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.@*RESULTS@#From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.@*CONCLUSIONS@#This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

Risk factors analysis of postsurgical gastroparesis syndrome and its impact on the survival of gastric cancer after subtotal gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors of postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy in gastric cancer and the impact of PGS on prognosis.</p><p><b>METHODS</b>Clinical data of 422 patients who underwent subtotal gastrectomy for gastric cancer in the Central Hospital of Huzhou Sity from January 2004 to May 2010 were analyzed retrospectively. Risk factors of PGS were indentified and the recurrence-free survival was compared between the patients with and without PGS.</p><p><b>RESULTS</b>PGS occurred in 42 patients (9.5%). Univariate analysis showed that: age over 65, combination of anxiety disorder, low-albuminemia in perioperative period, pyloric obstruction in preoperative period, high serume glucose level (≥ 11.2 mmol/L) in postoperative period, Billroth II (gastroenterostomy, operation time over 4 hours, using patient-controlled analgesia, or intravenous fluid over 3500 ml/d (all P<0.05) were prone to develop PGS. These might be potential clinical risk factors associated to PGS. Correlation analysis showed the number of clinical risk factors was positively correlated with the incidence of PGS (r=0.967, P<0.05). A total of 215 cases (50.9%) were followed up for 3-60 months. The mean recurrence-free survival time of patients with PGS was 26.1 months, which was shorter than that of those without PGS (33.4 months, P=0.029).</p><p><b>CONCLUSIONS</b>Gastric cancer patients with the clinical risk factors mentioned above are prone to develop PGS after subtotal gastrectomy. PGS is associated with poor prognosis.</p>

Surgery for T4 hypopharyngeal cancer and reconstruction after hypopharyngo-oesphagectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the surgical treatment of hypopharyngeal and cervical esophageal cancers and the ways of reconstruction after hypopharyngo-oesphagectomy, and to evaluate their efficacy.</p><p><b>METHODS</b>Twenty five patients with cancer of the laryngopharynx and cervical esophagus treated in our department between 1995 and 2007 were included in this study. Their clinical data were restrspectively analyzed. Among them, 17 cases had the tumor originated from the pyriform sinus, 3 of the posterior pharyngeal wall and 5 of the postcricoid region. Acording to the 2002 UICC criteria, all the tumors were stage T4, including 9 patients with cN0, 11 with cN1, and 5 with cN2 disease. The pharyngoesophageal defect reconstruction methods were as following: pharyngogastric anastomosis in 7 patients, free jejunal transplantion in 4, laryngotracheal flap in 8, and pectoralis major musculocutaneous flap in 6 patients. All patients were treated with modified and/or selective neck dissection. Among them, 8 cases received pre-operation radiotherapy, 17 received post-operative auxiliary radiotherapy.</p><p><b>RESULTS</b>There was no operation death case in this group. All patients were followed up for 3 to 5 years. Three patients died in the first year. According to Kaplan-Meier analysis, the 1-year survival rate was 88.0%, 3-year survival rate was 48.0%, and 5-year survival rate was 28.0%.</p><p><b>CONCLUSIONS</b>The use of primary repair of the defects of laryngopharynx and cervical esophagus expands the operative indication for cancers of the laryngopharynx and cervical esophagus, improves the survival rate and life quality of the patients. Regarding the repair method of choice, site of the tumor and size of the defect are the most important factors regarding choice of reconstruction method, while the patients' age and general condiction should also be considered to minimize the complications as more as possible.</p>

Study on inhibitory effect of matrine on cyclooxygenase-2 expression in colon cancer HT-29 cell line / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of matrine on cyclooxygenase-2 (COX-2) expression in colon cancer HT-29 cell line at the level of gene and protein.</p><p><b>METHODS</b>Levels of mRNA and protein expression of COX-2, and its synthesized product prostaglandin E2 (PGE2) of colon cancer HT-29 cell line were detected by RT-PCR, Western-blot, ELISA respectively before and after treatment of matrine in different concentrations.</p><p><b>RESULTS</b>Matrine had inhibitory effect on the mRNA and protein expression of COX-2, and synthesis of PGE2 in colon cancer HT-29 cell line, but had no effect on COX-1. When HT-29 cell line was treated with 2.0 mg/ml of matrine, the inhibitory rate on COX-2 mRNA expression were 100% at 6 hrs and 9 hrs after treatment; the inhibitory rate on PGE2 synthesis was 63.8 % at 9 hrs after treatment; and that on COX-2 protein expression was 48% and 100% 12 hrs and 24 hrs after treatment, respectively.</p><p><b>CONCLUSION</b>Matrine has selective inhibitory effect on gene transcription, protein expression and functional activity of COX-2 in HT-29 cell line, which is time-dependent and concentration-dependent within certain range of concentration and acting time.</p>

Recent research progress of anti-tumor mechnism matrine / 中国中药杂志

Matrine, as an active component of Chinese traditional medicine, has a great effect on anti-inflammation, anti-arrhythmia and anti-fibrosis of liver cell. But the recent evidences indicate that matrine also plays an important role in anti-tumor, such as inhibiting proliferation, inducing differation and apoptosis, reducing invasion and metastasis of tumor cell. In the review we summarized the recent research progress of anti-tumor mechanism of matrine.