Study on the role of CCL19 and AKT signaling pathway in the development of lung cancer / 中国职业医学

Objective To investigate the role of chemokine ligand 19 (CCL19) and protein kinase-B (AKT) signaling pathway in lung cancer development. Methods The human lung adenocarcinoma cell line, A549 cells, in logarithmic growth phase were randomly divided into five groups： blank control group, solvent control group, CCL19 treatment group, AKT inhibition group, and antibody neutralization group. The blank control group received no treatment. The other four groups were treated with dimethyl sulfoxide, CCL19, MK-2206 (AKT inhibitor), and a combination of CCL19 and MK-2206, respectively. Cell viability was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated using the cell scratch and transwell assays. The relative expression levels of Pan-AKT, p-AKT (Ser473), p-AKT (Thr308), E-cadherin (E-cad), N-cadherin (N-cad), and Snail proteins in A549 cells were detected using Western blotting. Lung cancer tissue samples from 60 patients with non-small cell lung cancer (NSCLC) were collected, and the expression of CCL19 and matrix metalloproteinase 9 (MMP9) proteins in the specimens was examined using immunohistochemistry. Results The survival rate of A549 cells in the AKT inhibition group and antibody neutralization group was lower than that in blank control group, solvent control group, and CCL19 treatment group (all P<0.05). The cell scratch assay result showed that the cell migration rate of the CCL19 treatment group was higher at 36.0 and 48.0 hours than those of the blank control group, solvent control group, AKT inhibition group, and neutralizing antibody group (all P<0.05). The Transwell assay result showed that the invasion amount of A549 cells in the AKT inhibition group was less than that in the CCL19 treatment group (P<0.05). Compared with the blank control group, the relative expression of E-cad protein in the CCL19 treatment group decreased, while the relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad and Snail proteins increased (all P<0.05). The relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad, and Snail proteins in A549 cells decreased (all P<0.05), and relative expression of E-cad protein increased (all P<0.05) in the AKT inhibition group and antibody neutralization group compared with the blank control group, solvent control group, and CCL19 treatment group. There was no significant difference in the expression of CCL19 and MMP9 in lung cancer tissues of NSCLC patients in Xuanwei City, Gejiu City, and other regions (all P>0.05). The expression of CCL19 and MMP9 in NSCLC patients with lymph node metastasis was higher than in patients without lymph node metastasis (all P<0.01). Conclusion CCL19 can promote the invasion and metastasis of lung cancer cells and induce epithelial-mesenchymal transition. Its expression level is related to lymph node metastasis in NSCLC patients. The AKT signaling pathway may be an important mechanism underlying lung cancer development.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.@*METHODS@#Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed.@*RESULTS@#Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.@*CONCLUSIONS@#ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Leptin-mediated ERK Signaling Pathway Promotes the Transformation of Rat Alveolar Type II Epithelial Cells Induced by Yunnan Tin Mine Dust / 中国肺癌杂志

BACKGROUND@#Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.@*METHODS@#Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.@*RESULTS@#Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.@*CONCLUSIONS@#Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.

Analysis on the Incidence and Economic Burden of Patients with Lung Cancer / 中国肺癌杂志

BACKGROUND@#The previous study has indicated that lung cancer has a high incidence and mortality in China, and has caused a large economic burden. The purpose of this study was to analyze the incidence and economic burden of lung cancer by analyzing the information on the home page of discharge history of lung cancer patients in Hebei Tumor Hospital, and to provide scientific basis for the prevention and treatment of lung cancer.@*METHODS@#The information of all of the discharges, new cases, surgical patients, age, gender, length of stay and hospitalization cost of lung cancer patients in Hebei Tumor Hospital from January 2012 to December 2019 were retrieved based on the medical record management system, and the incidence trend, gender and age distribution as well as the economic burden of the disease were statistically described.@*RESULTS@#The number of new cases of lung cancer increased year by year, from 2,235 cases in 2012 to 5,012 cases in 2019. The number of males always outnumbered females, but the gender ratio decreased year by year, from 2.25 in 2012 to 1.56 in 2019. Among new cases of lung cancer, the proportion of surgical treatment increased year by year, from 28.14% in 2012 to 44.83% in 2019. Except for 2012, the proportion of surgical operations in female patients was higher than that in male patients from 2013 to 2019. The proportion of surgical operations in male and female patients was 23.52% and 28.07% in 2013, and 36.14% and 58.37% in 2019, respectively. The median age at the onset of lung cancer has increased year by year, from 61 years old in 2012 to 63 years old in 2019. The median age of onset in all lung cancer patients was higher in males than in females. The number of new lung cancer patients and surgical patients both showed an increasing trend with the increase of age, and both reached the maximum value in the age group of 60-69 years old. With the increase of age, the number of patients gradually decreased. The median length of hospital stay for all discharged lung cancer patients or surgical patients decreased year by year, from 10 d and 19 d in 2012 to 8 d and 17 d in 2019, respectively, while the median hospitalization cost increased year by year. It increased from 10,611.46 yuan and 38,750.13 yuan in 2012 to 17,187.15 yuan and 84,030.16 yuan in 2019, respectively.@*CONCLUSIONS@#Lung cancer is still one of the main cancers endangering the health of Chinese residents. The incidence of lung cancer is increasing year by year, and the distribution of gender and age has certain characteristics. In order to reduce the number of cases and the economic burden, effective prevention and control measures should be formulated and medical reform should be strengthened.

Improvement of determination method of total anthraquinone in Rhei Radix et Rhizoma in Pharmacopoeia of the People’s Republic of China / 国际中医中药杂志

Objective:To improve the determination method for the total anthraquinone of the Rhei Radix et Rhizoma in the Pharmacopoeia of the People’s Republic of China, and compare this method with the method in the pharmacopoeia to determine the feasibility of such method. Methods:By changing the determination of total anthraquinone from biphasic hydrolysis to monophase hydrolysis, the method included in the pharmacopoeia was improved to determine the total anthraquinone content in Rhei Radix et Rhizoma. Chromatographic conditions were Symmetry C18 (4.6 mm × 250 mm, 5 μm) chromatographic column; the mobile phase is methanol-0.1% phosphoric acid water (85:15); the flow rate was 1 ml/min; the column temperature is 30 ℃; the detection wavelength is 254 nm. Results:The concentrations of aloe-emodin, rhein, emodin, chrysophanol, physcion in the range of 0.003 3-0.332 0 μg, 0.006 9-0.668 0 μg, 0.002 3-0.232 0 μg, 0.010 4-1.040 0 μg, 0.008 4-0.836 0 μg have good linear relationship with the peak area; RSDs of precision, stability and repeatability were less than 2%; the recovery rates of aloe-emodin, rhein, emodin, chrysophanol and physcion were 101.50%, 99.30%, 99.62%, 101.57%, and 103.11%, and the RSDs were less than 2%. Conclusion:The improvement method is simple, accurate, reliable and reproducible, which could be used for the quality control of Rhei Radix et Rhizoma.

Endocrine therapy combined with targeted therapy in hormone receptor-positive metastatic breast cancer / 中华医学杂志(英文版)

Increasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

Clinical effects of Xiaoer-Chaigui-Tuire granules in the treatment of mycoplasma pneumoniae pneumonia / 国际中医中药杂志

Objective To study the effects of Xiaoer-Chaigui-Tuire granules in the treatment of mycoplasma pneumoniae pneumonia (MPP). Methods A total of 200 children with mycoplasma pneumoniae pneumonia which conformed to the standard of admission were randomly divided into the control group (n=100) and the treatment group (n=100). The control group were treated with azithromycin, and the treatment group were treated with Xiaoer-Chaigui-Tuire granules combined with azithromycin. The temperature recovery time, cough disappeared time, asthma disappeared time, lungs rale disappeared time of the two groups were observed and compared. The serum IgG, IgM and IgA levels were detected by ELISA and the CD3, CD4, CD8 cell ratio of peripheral blood were detected by flow cytometry. Results The total effect rate of the treatment group was 95.0％ (95/100), significantly higher than 80.0％ (80/100) of the control group (χ2=10.286, P=0.001). The fever disappeared time (2.5 ± 0.3 d vs. 4.2 ± 0.9 d, t=17.004), cough disappeared time (3.0 ± 0.6 d vs. 4.5 ± 0.5 d, t=19.861), asthma disappeared time (3.1 ± 1.1 d vs. 4.0 ± 1.3 d, t=5.046), lungs rale disappeared time (4.2 ± 1.0 d vs. 8.4 ± 1.5 d, t=22.988) and of the treatment group were significantly lower than those of the control group (P<0.01). After treatment, the IgG (9.47 ± 1.63 g/L vs. 7.05 ± 1.46 g/L, t=11.059), IgM (1.87 ± 0.52 g/L vs. 1.53 ± 0.48 g/L, t=4.804) and IgA (1.79 ± 0.61 g/L vs. 1.20 ± 0.53 g/L, t=7.301) of the treatment group were significantly higher than those of the control group (P<0.01). After treatment, the blood CD3 levels (78.83％ ± 5.20 ％ vs. 57.48％ ± 4.09％, t=32.271), CD4 levels (40.27％ ± 3.42％ vs. 30.54％ ± 3.27％, t=20.563) of the treatment group were significantly higher than the control group, and the blood CD8 levels (21.15％ ± 2.90％ vs. 30.14％ ± 3.85％, t=18.651) of the treatment group were significantly lower than the control group (P<0.01). There was no significant difference in the incidence of adverse events between two groups (χ2=0.649, P=0.421). Conclusions The Xiaoer-Chaigui-Tuire granules combined with azithromycin for children with MPP has a good efficacy and low adverse events. They could relieve the clinical symptoms and improve the children's immune function.

Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA).</p><p><b>METHODS</b>From March 6, 2014 to December 10, 2014, 24 plasma samples from 20 patients with HER2-positive metastatic breast cancer who received systemic therapy were eligible. We used a panel for detection of hot-spot mutations from 50 oncogenes and tumor suppressor genes, and then used targeted next-generation sequencing (NGS) to identify somatic mutation of these samples in those 50 genes. Samples taken before their first trastuzumab administration and subsequently proven with clinical benefit were grouped into sensitive group. The others were collected after disease progression of the trastuzumab-based therapy and were grouped into the resistant group.</p><p><b>RESULTS</b>A total of 486 single-nucleotide variants from 46 genes were detected. Of these 46 genes, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene c-Kit (KIT), and tumor protein p53 (TP53) were the most common mutated genes. Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred m utations in the resistant group were associated with the resistance of targeted therapy. In addition, we detected a HER2 S855I mutation in two patients who had persistent benefits from anti-HER2 therapy.</p><p><b>CONCLUSION</b>Targeted NGS of cfDNA has potential clinical utility to detect biomarkers from HER2-targeted therapies.</p>

Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein / 中国药科大学学报

The purpose of this study was to synthesize and evaluate the necrosis target of MRI contrast agent based on rhein.The novel ligand 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid (DO3A-rhein) was synthesized by two-step acylation and two-step deprotection.The paramagnetic contrast agent gadolinium 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetate (Gd-DO3A-rhein) was obtained by coordination of Gd3+ with the synthesized ligand.Its necrosis affinity was evaluated by liver infarction and muscular necrosis on rat models.The MRI was performed before administration of Gd-DO3A-rhein and during 0 h to 12 h after administration of Gd-DO3A-rhein (0.1 mmol/kg),respectively,and Gd-DOTA was used as control.After MRI scanning,rats were sacrificed and necrotic tissues were stained using triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE).MRI images of liver infarction and muscular necrosis on rat models showed significantly enhanced signal intensity compared with normal tissues.The contrast ratios of necrotic liver/normal liver were 1.61 ±0.14 and 2.36 ±0.20 at 3 h and 12 h postinjection of Gd-DO3A-rhein (0.1 mmol/kg) respectively,demonstrating a significant difference compared with pre-administration of Gd-DO3A-rhein (1.16 ±0.10;P ＜ 0.05).The same results were obtained from necrotic muscles.These findings suggested that Gd-DO3A-rhein possessed the necrosis target and imaging capability of necrotic tissues.

Monitoring results of soil-transmitted nematodiasis in national surveillance site of Huaiyang County in Henan Province,2006-2015 / 中国血吸虫病防治杂志

Objective To understand the epidemic situation of soil-transmitted nematodiasis in the national surveillance site in Henan Province. Methods Over 1000 fecal samples from inhabitants in Huaiyang County of Henan Province,which was a national surveillance site,were collected each year from 2006 to 2015,the eggs of soil-transmitted nematodes and other intesti-nal helminths were examined by Kato-Kats technique. The cellophane swab method was used to detect Enterobius vermicularis eggs in children aged 3 to 12 years. In addition,the soil samples were collected from vegetable fields,lavatories,courtyards and kitchens of 10 families randomly selected in each year to examine Ascaris eggs by a modified saturated sodium nitrate floatation method. Results From 2006 to 2015,10419 persons were investigated,and the eggs of five species of intestinal helminths, Ascaris lumbricoides,Trichuris trichiura,hookworm,E. vermicularis,and Trichostrongylus orientalis,were detected,The aver-age infection rate of soil-transmitted nematodes in residents in Huaiyang County was 3.69%. The intensity of infection was mild and a family clustering was obvious. Both the infection rates of E. vermicularis in children and soil-transmitted nematodes in vil-lagers had no significant differences between different genders (both P>0.05). The infection rates of soil-transmitted nema-todes,A. lumbricoides and E. vermicularis all reached the highest in the age group of 1-10 years. For different education back-ground,the people with primary school education had the highest infection rate,and the infection rate showed a decreasing trend with the increase of the educational level. The infection rate of soil-transmitted nematodes in the national surveillance site in Henan Province showed a decreasing trend from 2006 to 2015. Unfertilized and fertilized A. lumbricoides eggs were detected in the soil samples,but the positive rate was very low. Conclusions In the recent 10 years,the infection rate of soil-transmit-ted nematodes in the national surveillance site in Henan Province shows a decreasing trend and maintains at a low level. The in-fection shows a family clustering. The children,especially those aged 3-9 years are the main infected population,and E. vermic-ularis infection is the key point of prevention and control.

Experimental study on bacteriostatic effect of recombinant human lactoferrin on Helicobacter pylori / 重庆医学

Objective To evaluate the bacteriostatic effect of recombinant human lactoferrin(rhLF) on Helicobacter(H .) py‐lori and its influence on CagA ,Ure and gastric mucosal IL‐8 .Methods The minimum inhibitory concentration(MIC)and the influ‐ence of different drug concentrations on the proliferation of H .pylori were detected .The effects of rhLF on the mRNA and protein expressions of CagA and Ure in H .pylori were detected by RT‐PCR and Western blot ,respectively .The animal study :Balb/c mice were adopted and assigned randomly into four groups ,including the standard triple+rhLF(group A) ,rhLF(group B) ,standard tri‐ple(group C) and normal saline(group D) .The histopathological HE staining was used to observe the gastric inflammation and ELISA was used to detect the IL‐8 level of gastric tissue in each group .Results MIC was 0 .5 mg/mL ,moreover rhLF inhibited the bacterial growth and proliferation with a concentration‐dependent manner .rhLF could reduce the expression of H .pylori major viru‐lence factor CagA ,mRNA and protein of Ure .Comparing the group A with the group B ,C and D ,the gastric mucosal inflammation score and the IL‐8 levels of gastric tissue homogenates had statistically significant differences(P<0 .05) .Conclusion rhLF inhibits the growth and proliferation of H .pylori ,moreover inhibit the expression of major virulence factor CagA in H .pylori ,mRNA and protein of Ure in different degrees ,weakens its pathogenicity ,meanwhile reduces the IL‐8 level in mice gastric mucosa ,and allevi‐ates H .pylori related gastric mucosal inflammatory response .

Effect of Xianxiong decoction on acute lung injury mice induced by lipopolysaccharide / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Xianxiong decoction on the mice with acute lung injury induced by lipopolysaccharide.</p><p><b>METHOD</b>Eighty female ICR mice were randomly divided into 8 groups: model group, Xianxiong decoction group, Daxianxiong decoction group, Xianxiong decoction group without Kansui Radix group, Xianxiong decoction group without Glycyrrhizae Radix et Rhizoma group, Glycyrrhizae Radix et Rhizoma and Kansui Radix group, normal group and control group. Animals of each group, except normal group, were undertaken intraperitoneal injection and intranasal inhalation of lipopolysaccharide (LPS) on day 1, 2, 3 to establish acute lung injury (ALI) model. 30 min after modeling, 0.2 mL corresponding drugs were administrated to each mice, dexam ethasone and normal saline were given to the mice of control group and normal group respectively. White blood cell in blood, neutrophil percentage of blood and bronchoalveolar lavage fluid (BALF) supernatant, the ratio of wet and dry lung tissue ( W/D), histopathological changes of lung tissue were estimated. Sixty ICR mice were randomly divided into normal, model, control, high, middle and low dose Xianxiong decoction groups and were modeled in the same way. ELISA was applied to detect the level of NF-kappaB, TNF-alpha and IL-6 in BALF, PCR for NF-kappaB and TNF-alpha mRNA in lung tissue, and Western blot for NF-kappaB and TNF-alpha. Half of 20 ICR mice were administrated with Xianxiong decoction of its maximum tolerant normal saline.</p><p><b>RESULT</b>Compared with model group, the number of WBC in blood of Xianxiong decoction group mice decreased (P < 0.01), percentage of neutrophils in both blood and BALF decreased as well (P < 0.01, P < 0.05); it also significantly reduced the ratio of W/D (P < 0.01); and found the alveolar wall, the number of inflammatory cells infiltrating improved, compared with model group. Xianxiong decoction reduced the level of NF-kappaB, TNF-alpha and IL-6 in BALF (P < 0.01, P < 0.01, P < 0.05); its high and low dose groups only found TNF-alpha level declined. Five mice died 24 h after administration of Xianxiong decoction which indicated its toxicity when other influential factors were considered.</p><p><b>CONCLUSION</b>Xianxiong decoction is effective on the ALI mice induced by LPS, but it is of toxicity at 3 g x mL(-1).</p>

The role of Smad7 in oral mucositis

Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair and protect ulcerated oral mucosa without promoting cancer cell growth. Oral mucositis is the result of complex, multifaceted pathobiology, involving a series of signaling pathways and a chain of interactions between the epithelium and submucosa. Among those pathways and interactions, the activation of nuclear factor-kappa B (NF-κB) is critical to the inflammation process of oral mucositis. We recently found that activation of TGFβ (transforming growth factor β) signaling is associated with the development of oral mucositis. Smad7, the negative regulator of TGFβ signaling, inhibits both NF-κB and TGFβ activation and thus plays a pivotal role in the prevention and treatment of oral mucositis by attenuating growth inhibition, apoptosis, and inflammation while promoting epithelial migration. The major objective of this review is to evaluate the known functions of Smad7, with a particular focus on its molecular mechanisms and its function in blocking multiple pathological processes in oral mucositis.

Exploratory study of chemotherapy combined with endocrine therapy for metastatic breast cancer after standard treatment failure / 肿瘤研究与临床

Objective To analyze the clinical value of chemotherapy combined with endocine therapy after standard treatment failure for advanced metastatic breast cancer.Methods 30 metastatic breast cancer patients after standard treatment failure were analyzed.Etoposide (75-100 mg/d) wasused on days 1-10,followed by 11 days of rest combined with medroxyprogesterone 0.5 g,twice per day,or megestrol 160 mg/d for 21 days.Clinical effects and life quility were analysed.Results The median treatment line of this therapy was 6 (range 3-9).The clinical benefit rate is 16.7 ％ (5/30),and the median progression free survival (PFS) was 4.0 months (range 1.0-13.0 months).Conclusion The combination of chemotherapy (etoposide) and endocrine therapy (progesterone) is a choice of treatment after standard drug failure for advanced mastatic breast cancer patients.

Application of Dua-energy Virtual Non-contrast Imaging in Evaluating Enlarged Cervical Lymph Nodes / 中国医学影像学杂志

Purpose To investigate the value of dual-source CT with dual-energy virtual non-contrast imaging in the diagnosis of cervical lymph node disease. Materials and Methods The dual-energy scan data of 126 lymph nodes from 50 patients confirmed pathologically were reviewed. The difference of average CT value, signal to noise ratio, contrast to noise ratio, image subjective assessment and lesion detectability between virtual non-contrast imaging and conventional non-contrast scan were analyzed. The radiation dose of virtual non-contrast imaging and real non-contrast imaging of cervical lymph node were also compared. Results ①The consistency of virtual plain scan combined with dual-energy contrast imaging in the diagnosis of six typical pathological types were all satisfactory (Kappa>0.7, P0.05).③ Compared with conventional enhanced scan, dual-energy phases reduced radiation dose by about 19%. Conclusion Dual-energy virtual non-contrast imaging combined with contrast imaging can provide clear images in the diagnosis of enlarged cervical lymph nodes and reduce radiation dose of subjects, thus can be expected to replace real scan.

Evaluation of Watch PAT as a diagnosing test for patients with obstructive sleep apnea hypopnea syndrome / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>This study aimed to test the accuracy of the watch peripheral arterial tone (Watch PAT) in diagnosing the obstructive sleep apnea hypopnea syndrome (OSAHS) and its influencing factors.</p><p><b>METHODS</b>Thirty five outpatients who had a chief complaining of sleep snoring were recruited to receive Watch PAT test and polysomnography (PSG) simultaneously. The results of PSG were manually analyzed by an experienced technician, while the results of Watch PAT were automatically analyzed by software.</p><p><b>RESULTS</b>There was a trend that the apnea hypopnea index (AHI) of PSG was significantly higher than that of Watch PAT (P = 0.06) in the 35 patients studied, however, these two variables were significantly correlated (P < 0.001), and the correlation coefficient was as high as 0.955. A linear regression analysis which used the AHI of Watch PAT to predict the AHI of PSG also concluded same result and the equation was AHI (PSG) = 0.944 + 1.030AHI (Watch PAT), P < 0.001. The analysis which used ROC curve to test the diagnostic efficiency of Watch PAT concluded that the area under the curve could reach to 0.953 (P < 0.001), and if an AHI (Watch PAT) threshold of ≥ 8.65 was used as the cut-off point in this study, the sensitivity and specificity could reach to 92.3% and 100.0%. The absolute values of the differences (AVD) between the AHI of Watch PAT and the AHI of PSG were also calculated as a criterion for grouping the 35 patients studied, then it could be found that there was a trend that the BMI of patients who had an AVD ≥ 5 were higher than that of patients who had an AVD < 5 (P = 0.077).</p><p><b>CONCLUSIONS</b>The Watch PAT is highly sensitive in the diagnosis of OSAHS, it can be used as a simple and reliable method for screening people with suspicious OSAHS. However, the accuracy of diagnosis may be relatively low in patients who have a great BMI.</p>

Establishment and characterization of lung adenocarcinoma cell line XLA-07 / 中华病理学杂志

<p><b>OBJECTIVE</b>To establish and characterize a lung adenocarcinoma cell line from a female patient in Xuanwei, Yunnan province.</p><p><b>METHODS</b>Surgical specimen of the lung adenocarcinoma was obtained and cultured immediately in RPMI 1640 medium with 10% fetal bovine serum and 10(5) U/L penicillin and 100 mg/L streptomycin. When stable proliferation of the cells was achieved after over 40 passages in culture, the biological features of the cell line were investigated by cell morphology, karyotyping, protein marker expression [cytokeratins (CKs), epithelial membrane antigen (EMA) and CD proteins], growth kinetics, cell cycle phase distribution, mitotic index, colony formation in soft agar, cell invasion and tumorigenicity in Balb/c nude mice.</p><p><b>RESULTS</b>The established cell line was stably cultured for over 80 passages during a one-year period as an anchorage-dependent monolayer of short spindle, polygonal to epithelioid cells under phase contrast microscope. Microglandular cavities and disordered microfilaments were observed under transmission electron microscope. The growth curve presented in an "S" shape with the cell population doubled every 46.7 hours. The mitotic index was 1.5% and the colony formation rate was 8.3%. The cell cycle distribution included 76.9% in G(0)/G(1), 15.1% in S and 8.0% in G(2)/M. The cell line displayed a hypotriploid karyotype with a mode of 66 chromosomes and a median of 64 chromosomes. The cells expressed CK7, CK8, CK (Pan) and EMA by immunohistochemistry. A high level of cell surface expression of CD13 and CD59 was evident by flow cytometry. The cells were able to penetrate Matrigel in vitro but failed to form a stable xenograft in nude mice.</p><p><b>CONCLUSION</b>A new human lung adenocarcinoma cell line, designated as XLA-07, is successfully established from a Xuanwei lung cancer patient.</p>

Overnight hemoglobin-oxygen saturation monitoring the first day following revised uvulopalatopharyngoplasty in patients with obstructive sleep apnea hypopnea syndrome / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of overnight arterial oxygen saturation (SaO2) the first day after upper airway reconstruction surgery in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).</p><p><b>METHODS</b>One hundred and thirteen subjects with OSAHS underwent revised uvulopalatopharyngoplasty (H-UPPP), among them, 46 subjects underwent same phase transpalatal pharyngoplasty under general anesthesia. After transferred to general ward from intensive care unit the first day after operation they received an overnight hemoglobin-oxygen saturation monitoring.</p><p><b>RESULTS</b>Twelve subjects (10.2%) had lower lowest SaO2 than preoperative value. ≥ 0.03 oxygen desaturation index (ODI3) decreased in an median of 36.9 [16.9; 52.2] events/hour compared with preoperative values (Z = -9.221, P < 0.001). One subjects (0.8%) had increased ODI3. No hemorrhages, cardiovascular complications or airway obstruction occurred. The subjects with any two of the following conditions (n = 51) had lower average SaO2, lowest SaO2 and higher ODI3 than the others (n = 62, Z were -3.084, -4.083 and -4.593, P < 0.001). The three subjects were: (1) BMI ≥ 27.0 kg/m(2); (2) Lowest SaO2 < 0.600; (3) AHI ≥ 60.0 events/h.</p><p><b>CONCLUSIONS</b>Some OSAHS patients had a decreased LSaO2 than preoperative values the first day after operation. As part of a patient safety initiative, SaO2 monitoring for those who have high risk for hypoxemia is necessary.</p>

Effects on cellular immunity caused by intravenous infusion of allogenic rhesus mesenchymal stem cells / 白血病·淋巴瘤

ObjectiveTo study the changes of cellular immunity caused by intravenous infusion of allogenic rhesus mesenchymal stem cells (MSCs).MethodsMSCs were isolated and cultured.Then the immunomodulatory effects after MSCs infusion were evaluated by means of peripheral blood counts,mixed lymphocyte reaction (MLR) and analysis of lymphocytic subgroup. ResultsMSCs of rehsus were successfully cultivated. No acute toxicities or GVHD were observed in recipients. No obvious changes of peripheral blood counts were present. Recipients A2, A3, A4 were administered with MSC by 4.0 ×105/kg, 1.0 ×106/kg, 2.0×106/kg respectively and relative reaction (RR) of MLR decreased 14 days post MSCs infusion: from 46±2.6 ％to 40.4±1.73 ％ (F =10.19, P =0.023), from (40.9±2.3) ％ to (33±2.1) ％ (F =2.593, P =0.013), from 48.3±2.0 ％ to 39±1.0 ％ (F =28.431, P =0.003) respectively. The decrease degree (ARR) was positively related to the amount of MSCs(F =27.413, P =0.038). RR was restored within 30 days post MSCs infusion. After MSCs infusion, CD3+ CD3+CD4+ and CD3+CD8+ T-lymphocytes decreased in recipient A4, who was administered with the largest number of MSCs, and restored within 30 days. ConclusionMSCs infusion without any other treatment could temporarily inhibit immunity of T lymphocytes in MLR and the immunity inhibition was positively related to the amount of MSCs.The specific immunological characteristics of MSCs were demonstrated with extensive prospect in clinical research.

Efficacy and safety of regimens of capecitabine-based chemotherapy in the treatment of advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.</p><p><b>METHODS</b>Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.</p><p><b>RESULTS</b>Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).</p><p><b>CONCLUSIONS</b>The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.</p>