Chinese Medicine in Treatment of Gastrointestinal Dysfunction After Gastric Cancer Surgery： A Review / 中国实验方剂学杂志

Gastric cancer is the most prevalent gastrointestinal tumor in China， threatening the life and health of patients. Surgery is one of the available therapies， which， however， induces postoperative gastrointestinal dysfunction （PGD） and other common complications. The pathogenesis of PGD is still unclear and no efficient targeted drug is available. In addition， the limited treatment measures fail to effectively improve gastrointestinal function. As a result， patients generally suffer from low quality of life and poor prognosis. In Chinese medicine， PGD belongs to the categories of "vomiting"， "stuffiness and fullness"， "regurgitation"， "abdominal distension"， "intestinal impediment"， and "intestinal accumulation". In recent years， there has been an explosion of research on the PGD of gastric cancer in Chinese medicine， and many research results have been obtained. On this basis， this study introduced PGD in modern medicine， and causes and pathogenesis， syndrome differentiation-based treatment， and clinical studies of PGD. It was found that diverse internal and external treatments are available in Chinese medicine for PGD such as internal use of Chinese medicine， Chinese medicine enema， auricular point seed-embedding， acupuncture， and moxibustion， which feature ease of implementation， small side effects， definite efficacy， and significant effect in combination with other therapies. This paper summarized the ideas and measures for treatment of PGD of gastric cancer by Chinese medicine， the research outcomes， limitations， and research directions， which can serve as a reference for further research on treatment of PGD of gastric cancer by Chinese medicine.

Multicenter study of venetoclax-based combined regimen in treatment of adult acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

Progress of tumor-associated macrophages in tumors / 肿瘤研究与临床

Tumor-associated macrophage (TAM) is a macrophage infiltrating around tumor cells, which can be divided into two categories including classical activated macrophages (M1) and alternately activated macrophages (M2). On the whole, it shows the phenotype of M2 macrophages that promote immune escape of tumor cells. With the in-depth study of the immune function of the body, the studies have indicated that TAM is highly malleable and can be transformed into each other with the change of tumor microenvironment. TAM plays a very important role in tumor occurrence, development, invasion and metastasis, and its classification and quantity may also be used as an index to judge the prognosis of tumors. Therefore, TAM is a feasible potential target for the treatment of cancer. This paper reviews the role of TAM in tumorigenesis and development.

Serum nuclear magnetic resonance-based metabolomics in patients with diffuse large B-cell lymphoma: a pilot study / 白血病·淋巴瘤

Objective To discover new biomarkers for diffuse large B-cell lymphoma (DLBCL) diagnosis and prognosis using nuclear magnetic resonance (NMR)-based serum metabolomics. Methods High-resolution serum 1H NMR spectra were collected from 7 DLBCL patients and 7 healthy controls. Spectra were processed using stoichiometry pattern-recognition methods [principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA)]. Results Significant difference (P <0.05) in 9 metabolites was observed between DLBCL and healthy control by OPLS-DA (variable interpretation rate R2Y ＝ 99.0 % and prediction rate Q2＝ 94.5 %). Compared with the healthy control group, higher levels of lactate (r ＝0.60, P<0.01), glycine (r ＝0.84, P<0.001), creatine (r ＝0.63, P<0.01), and choline (r ＝0.69, P< 0.01), lower levels of acetate (r＝ -0.88, P< 0.001), high-density lipoprotein (r＝ -0.77, P< 0.001), citrate (r ＝-0.82, P<0.001), glutamine (r ＝-0.53, P<0.05) and phosphocholine/glycerophosphocholine (r ＝-0.62, P<0.001) were detected in the serum samples of DLBCL. Conclusion The results of this study offer an evidence for significant changes between DLBCL patients and healthy people in serum metabolite profiles utilizing NMR-based serum metabolomics.

Isolation and identification of lung cancer stem like cells from human lung adenocarci-noma cell lines / 中国肿瘤临床

Objective:To isolate cell spheres containing cancer stem cells (CSCs) from lung cancer cell lines (A549 and H1299) and iden-tify their biological characteristics. Methods:By adopting the method of serum-free suspension culture, A549 cells and H1299 cells were cultured on no-adhesion plate to form tumor spheres. Clone assay, CCK-8 assay, and Transwell assay were employed to observe proliferation, self-renewal and invasion of tumor spheres. Besides, RT-PCR was performed to compare the expression levels of stem cell markers between sphere cells and adherent cells. Adherent A549 cells and A549 cell spheres were inoculated subcutaneously in nude mice and the tumor growth was assessed. Results:Isolated CSCs from A549 cells and H1299 cells in serum-free medium (SFM) without adhesion could grow as floating cell spheres. The results demonstrated that the self-renewal, proliferation and invasion of A549 and H1299 sphere cells were stronger than parent cells (P<0.05). When compared with adherent cells, the mRNA level of expres-sion of cell spheres' stem cell markers (Oct4 and Nanog) were significantly high (P<0.05) and A549 spheres had a stronger tumorigenici-ty in nude mice. Conclusion:SFM without adhesion can be a quick and easy method to construct stem cells model from human lung adenocarcinoma cell lines A549 and H1299.

Clinical features and risk factors for infections in adult acute leukemia after chemotherapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical characteristics of infections in adult acute leukemia （AL）patients during chemotherapy in hospital, and identify the risk factors for infections.</p><p><b>METHODS</b>A retrospective study of patients with AL who underwent chemotherapy between July 2010 and Dec 2014 in the First Affiliated Hospital of Xiamen University was conducted. Clinical features and risk factors for infections were analyzed.</p><p><b>RESULTS</b>191 patients with AL received a total of 728 courses of chemotherapies. During these admissions, 385（52.9%) infections episodes occurred. The common infections sites were lower respiratory tract infection（36.3%，153/374）, bloodstream infection（17.1%, 64/374）, oral infection（13.6%，51/374）, and perianal infection（13.4%, 50/374）. 164 strains of pathogenic bacteria were detected. Gram- negative bacteria were recorded in 59.1% of documented pathogens, and Gram- positive bacteria were responsible for 32.9% of infections. Multivariate unconditioned logistic analysis of factors identified consistent independent risk factors for no completely remission（OR=0.142, P< 0.001）, duration of neutropenia longer than 7 days（OR=12.764, P<0.001）, general wards（OR=1.821, P< 0.001）, and hospitalization interval longer than 10 days（OR=0.720, P=0.039）.</p><p><b>CONCLUSION</b>Infections after chemotherapy for AL continues to be common. AL patients with induction chemotherapy or severe neutropenia faced an increased risk of infections by multivariate analysis. And patients with short-term stay or laminar flow wards seem to be less susceptible to infections.</p>

Clinical implications of tumor necrosis factor-α in lymphomas / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the levels of tumor necrosis factor-α (TNF-α) in tissue or plasma and its clinical implications in different types of lymphoma.</p><p><b>METHODS</b>The levels of TNF-α in paraffin tissue or plasma samples were detected by immunohistochemistry or ELISA assay in 88 lymphoma patients and 88 healthy controls. Univariate and multivariate Cox regression analysis were used to identify the correlation between Ann Ardor stage, blood cells count, bone marrow abnormalities, erythrocyte sedimentation rate (ESR), serum ferritin and TNF-α expression.</p><p><b>RESULTS</b>The levels of TNF-α had significant difference in different types of lymphoma (P<0.05). High positive and levels in Hodgkin lymphoma [HL, 72.72% and (43.12±15.28) ng/L], aggressive non-HL [NHL, 67.86% and (40.73±16.65) ng/L], and indolent NHL [57.14% and (53.18±20.47) ng/L]. Cox regression analysis showed that Ann Ardor stage, bone marrow abnormalities, ESR, and the levels of TNF-α were independent risk factors for lymphoma with poor prognosis.</p><p><b>CONCLUSION</b>As an independent factor, TNF-α may play a role in the development of lymphoma and is an important prognostic factor.</p>

Molecular mechanisms of Survivin gene expression regulated by imatinib / 白血病·淋巴瘤

Objective To investigate the influences of imatinib on Survivin gene expression in bcr-abl-transformed leukemia cells.Methods Firstly,PCR and Western blot were carried out to detected Survivin expression with imatinib treatment in 32Dcl3 and 32D-bcr-abl cell lines.Then the luciferase reporter plasmids containing human Survivin promoter as well as its deletion and site-directed mutation were constructed to identify the essential responsive elements for suppressing Survivin promoter activity by imatinib.Chromatin immunoprecipitation was performed to confirm the binding of c-myc to Survivin promoter.10058-F4,a small molecule c-myc inhibitor,was used to disrupt c-myc activity and evaluate its anti-leukemic effect combined with imatinib.Results Both of mRNA and protein level of Survivin in bcr-abl-transformed cells were downregulated upon imatinib treatment.The decrease of Survivin expression was controlled at the transcriptional level through a mechanism in which imatinib repressed survivin promoter activity by disturbing the interaction between c-myc and E-box elements.Interruption of c-myc activity by 10058-F4 exerted an anti-leukemia effect with enhancing the sensibility of K562/G01 cells to imatinib.Conclusion Imatinib down-regulates Survivin expression through c-myc-mediated transcription and interference with c-myc might be a potential utility for treatment of imatinib resistant leukemia.

Effects of Jianpi Huoxue Decoction on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide / 中西医结合学报

OBJECTIVE: To observe the effects of Jianpi Huoxue Decoction, a compound Chinese herbal medicine, on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide (LPS). METHODS: SD rats were divided into normal, control liquid diet, ethanol liquid diet and ethanol liquid diet plus Jianpi Huoxue Decoction group. Rats were administrated with Jianpi Huoxue Decoction or distilled water via gastrogavage for 4 weeks after administration with ethanol or control liquid diet for 2 weeks respectively. After that, rats in each group were stimulated with LPS via gastrogavage for 3.5 h and harvested. Alanine aminotransferase (ALT) in serum and triglyceride (TG) in liver were analyzed. Pathological changes in liver tissues were observed in HE staining section. Tumor necrosis factor-alpha(TNF-alpha) in portal vein plasma was assayed by ELISA. The protein expressions of CD68, Toll-like receptor 4 (TLR4), phosphorylation-I kappa B (P-I kappa B) and TNF-alpha in liver were evaluated with Western-blotting. RESULTS: After the treatment with Jianpi Huoxue Decoction, the pathologic changes in liver tissue were lightened, levels of ALT in serum, TG in liver and TNF-alpha in portal vein plasma were decreased, and the protein expressions of CD68, TLR4, P-IkappaB and TNF-alpha in liver were reduced. CONCLUSION: Jianpi Huoxue Decoction can inhibit Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and LPS.

Preparation of Lieber-DeCarli liquid diet induced alcoholic hepatic injury model in rats / 中西医结合学报

OBJECTIVE: Duplicating the classical alcoholic hepatic injury model, to provide an ideal animal model for research on prevention and treatment of hepatic injury. METHODS: According to the prescription of Lieber-DeCarli, the same calorie fluid animal feed, which contained ethanol or non-ethanol, was prepared. Twenty-three rats were divided into normal control group (n=5), control liquid diet group (n=9), ethanol liquid diet group (n=9). Rats in the normal control group were fed normal diet, and rats in the control liquid diet group and ethanol liquid diet group were fed the corresponding diet for eight weeks. The pathologic changes of hepatic tissue were observed. The activities of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver tissue gamma-glutamyltransferase (gamma-GT), the content of triglyceride (TG), and the lipid peroxidation by-products were assayed. RESULTS: Compared to the normal control and the control liquid diet groups, the activities of ALT, AST, and gamma-GT, and the lipid peroxidation by-products increased significantly in the ethanol liquid diet group. The pathological changes of cellular swelling and fatty degeneration in the ethanol liquid diet group were severe. CONCLUSION: Alcoholic hepatic injury model can be successfully duplicated by Lieber-DeCarli prescription.

Clinical investigation on characteristics of traditional Chinese medical syndrome of hepatocirrhosis / 中西医结合学报

OBJECTIVE: To explore the characteristics of traditional Chinese medical syndrome (TCM syndrome) of hepatocirrhosis. METHODS: Clinical information from the four diagnosis methods of traditional Chinese medicine (TCM) and related laboratorial indexes were systematically collected from 223 hepatocirrhosis cases, and the multi-statistical methods including systematic cluster analysis, principal component analysis, stepwise discrimination and variance analysis were made with the software SAS 6.11. RESULTS: Multi-analysis showed that there were 3 categories of syndrome characteristics. Type 1 (134 cases): damp heat, blood stasis, deficiency of liver and spleen Qi; Type 2 (62 cases): deficiency of both Qi and Yin with severe deficiency of Qi, heat with severe dampness, blood stasis; Type 3 (27 cases): deficiency of both Qi and Yin with severe deficiency of Yin, stasis and heat or dampness. Analysis of the changes of the related laboratorial indexes among the three types of syndrome showed that Type 1 mainly manifested asthenia syndrome with sthenia syndrome, and its indexes of AST, ALT, GGT levels were markedly higher than those of Type 2 and Type 3, both of which mainly showed sthenia syndrome with asthenia syndrome, and that Type 3 was in active inflammation, deficiency of both Qi and Yin (deficiency of Yin > deficiency of Qi), and its FN, Alb, FV, FVII, PLT, PCT levels were obviously reduced. CONCLUSION: The multi-statistical methods can reveal the characteristics and regularity of TCM syndrome of hepatocirrhosis, and the 3 categories of syndrome characteristics basically conform to clinical manifestations. The result of TCM syndrome distribution and laboratorial indexes infer that damp heat is the pathological basis of hepatocirrhosis, and the degree of liver function disorder and liver damage may be the pathological basis of deficiency of Yin of both liver and kidney.