Objective To investigate the effects of fructose exposure on mitochondrial oxidative damage in M2-type macrophages and elucidate the regulatory role of protein phosphatase 2A(PP2A)in the process using its specific activator ABL127,an inhibitor of protein phosphatase methylesterase-1(PPME-1).Methods ① Immortalized mouse bone marrow-derived macrophages Ana-1 were subjected and grouped into M0(conventional culture),M2(treated with 20 ng/mL IL-4 for 24 h),and M2+Fru groups(IL-4 plus 0.04,0.20,1.00,or 5.00 mmol/L fructose).Cell viability was assessed with CCK-8 assay.Number of mitochondria,total and mitochondrial levels of reactive oxygen species(ROS),and mitochondrial membrane potential(ΔΨM)were measured using fluorescent probes.Total and demethylated PP2Ac protein levels were detected by Western blotting.② Ana-1 cells were also divided into M0,M2,M2+Fru(20 ng/mL IL-4+5.00 mmol/L fructose,24 h),and M2+Fru+ABL127(20 ng/mL IL-4+5.00 mmol/L fructose+1.00 μmol/L ABL127,24 h)to investigate PP2A-mediated mechanisms.Numbers of mitochondria and lysosomes,ROS level,and ΔΨM were detected via fluorescence assays.Expression of mitophagy-related proteins,PTEN induced putative kinase 1(PINK1),P62,microtubule-associated protein light chain 3(LC3),and voltage-dependent anion channel(VDAC)was evaluated by Western blotting,and the mRNA levels of M2 markers,found in inflammatory zone 1(Fizz1),arginase-1(Arg-1),and TGF-β were measured using RT-qPCR.Results ① Compared with the M2 group,fructose treatment at a concentration ranging from 0.04 to 5.00 mmol/L showed no effect on cell viability in M2 macrophages,but increased total ROS level in a dose-dependent manner(P<0.05).Fructose of 5.00 mmol/L resulted in significantly elevated mitochondrial ROS and mitochondrial quantity(P<0.05),reduced ΔΨM(P<0.05),up-regulated demethylated-PP2Ac(P<0.05),and no changed total-PP2Ac protein level.② Compared with the M2+Fru group,the addition of ABL127 led to decreased number of mitochondria but increased number of lysosomes(P<0.01),up-regulation of PINK1,LC3Ⅱ and VDAC proteins,down-regulation of P62(P<0.05),reduced total and mitochondrial ROS levels,and enhanced ΔΨM(P<0.01).The mRNA expression of Fizz1,Arg-1,and TGF-β was notably decreased in the M2+Fru group than the M2 group(P<0.05),and the levels were rescued by ABL127 treatment(P<0.05).Conclusion Fructose induces PP2Ac demethylation and then mitochondrial oxidative damage in M2-type macrophages.PP2A activation promotes mitophagy and reverses fructose-induced damage.

Objective: To investigate the factors influencing the development of gastric cancer in Chinese populations, so as provide insights into creating a model for predicting gastric cancer incidence among Chinese populations. Methods: The case-control and cohort studies pertaining to factors affecting the development of gastric cancer were retrieved in electronic Chinese and English databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science and Embase from their inception until September 30, 2021. A meta-analysis was performed using R package version 4.1.0. Sensitivity analysis was performed using the “leave-one-out” evaluation procedure, and the publication bias was evaluated using the Egger regression test and the trim-and-fill procedure. Results: A total of 5 301 publications were screened and 116 eligible studies were included in the final analysis, including 103 case-control studies and 13 cohort studies, which covered approximately 3.23 million study subjects. A total of 45 factors affecting the development of gastric cancer were collected, and there were less than 4 publications reporting 7 factors, which were only qualitatively described. There were 38 factors included in the final meta-analysis. A total of 21 factors were identified as risk factors of gastric cancer, including a history of gastrointestinal diseases (pooled OR=4.85, 95%CI: 3.74-6.29), H. pylori infection (pooled OR=3.18, 95%CI: 2.35-4.32), binge eating and drinking (pooled OR=2.88, 95%CI: 2.09-3.97) and a family history of tumors (pooled OR=2.78, 95%CI: 2.17-3.56), and 10 factors as protective factors, including vegetable intake (pooled OR=0.48, 95%CI: 0.38-0.61), tea consumption (pooled OR=0.55, 95%CI: 0.47-0.64), administration of aspirin (pooled OR=0.53, 95%CI: 0.31-0.92) and administration of statins (pooled OR=0.59, 95%CI: 0.44-0.80). Sensitivity analyses of eating moldy food frequently, white meat intake, favoring spicy food and administration of sulfonylureas were not robust. Following correction with the trim-and-fill procedure, there was still a publication bias pertaining to high income, diabetes, administration of stains, alcohol consumption, tea consumption and white meat intake. Conclusions The development of gastric cancer is associated with a medical history of gastrointestinal disease, H. pylori infection, family history of tumors and poor dietary habits. Risk and protective factors of gastric cancer are recommended to be included in models used to predict gastric cancer incidence among Chinese populations.

Objective:To explore clustered epidemic of COVID-19 in Liaocheng city and analyze infection status and chain of transmission of the cases.Methods:A joint investigation team of emergency response for COVID-19 epidemic by CDC professional workers of Liaocheng city and district at two levels on January 30, 2020. According to a indicator case from ZH supermarkets, close contacts and related subjects were tracked and screened on February 1, including ZH supermarket employees, family members having contact history with related cases during January 13-26, supermarket clients during January 16-30 and family members of related cases. an epidemiological investigation was carried on and their swab of nose/throat were collected and were sent to Liaocheng CDC laboratory, real-time fluorescence quantitative RT-PCR was used to detect nucleic acids of SARS-CoV-2.Results:a total of 8 437 people were screened during January 30 to February 9, 2020 (120 employees of supermarket, 93 family members, and 8224 clients of supermarket). The epidemic was caused by ZH cases and brought clustered cases in four families. A total 25 cases of SARS-CoV-2 infection, the total infection rate of subjects was 0.30% (25/8 437) with 22 confirmed cases (0.26%, 22/8 437) and 3 asymptomatic patients (0.04%, 3/8 437), asymptomatic patients accounted for 12.00% (3/25) of all infection cases. The infection rates of supermarket employees, family members of confirmed cases and supermarket clients were 9.17% (11/120), 12.90% (12/93) and 0.02% (2/8 224).Conclusions:This was a cluster epidemic caused by one imported case of COVID-19 in a supermarket of Liaocheng city. Prevention and control of cluster epidemic should be focused on chain of community transmission and family cluster cases. It must also be an attention for transmission risk of asymptomatic patients.

Purpose: Numerous studies have shown that the frequency of myeloid-derived suppressor cells (MDSCs) is associated with tumor progression, metastasis, and recurrence. Chemokine (C-C motif) ligand 3 (CCL3) may be secreted by tumor cells and attract MDSCs into the tumor microenvironment. In the present study, we aimed to explore the molecular mechanisms whereby CCL3 is involved in the interaction of breast cancer cells and MDSCs. Methods: The expression of CCL3 and its receptors was investigated using real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The cell counting Kit-8, wound healing, and transwell assays were performed to study cell growth, migration, and invasion. Cell cycling, apoptosis, and the frequency of MDSCs were investigated through flow cytometry. Transwell assays were used for co-culture and chemotaxis detection. Markers of the epithelial-mesenchymal transition (EMT) were determined with western blotting. The role of CCL3 in vivo was studied via tumor xenograft experiments. Results: CCL3 promoted cell proliferation, migration, invasion, and cycling, and inhibited apoptosis of breast cancer cells in vitro. Blocking CCL3 in vivo inhibited tumor growth and metastases. The frequency of MDSCs in patients with breast cancer was higher than that in healthy donors. Additionally, MDSCs might be recruited by CCL3. Co-culture with MDSCs activated the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway and promoted the EMT in breast cancer cells, and their proliferation, migration, and invasion significantly increased. These changes were not observed when breast cancer cells with CCL3 knockdown were co-cultured with MDSCs. Conclusion CCL3 promoted the growth of breast cancer cells, and MDSCs recruited by CCL3 interacted with these cells and then activated the PI3K-Akt-mTOR pathway, which led to EMT and promoted the migration and invasion of the cells.

Objective To analyze the clinicopathological characteristics and prognosis of different subtypes of breast cancer patients with bone metastasis.Methods For this study, we recruited 300 primary breast cancer patients with bone metastasis treated at the Department of Oncology, the First Affiliated Hospital of Xi`an Jiaotong University, between September 1, 2007 and September 1, 2011.We also retrospectively analyzed their clinical and follow-up data.Results The percentage of Luminal A, Luminal B, human epidermal growth factor receptor-2 (HER-2) overexpression and triple negative subtypes in all the bone metastatic breast cancer patients was 59.0％, 16.0％, 13.7％ and 11.3％, respectively.Age, tumor size and histologic grade significantly differed among the four subtypes (P<0.05).However, there were no significant differences in menopausal status, lymph node metastasis, histological type or lymphovascular invasion among different subtypes (P>0.05).The median survival time of Luminal A breast cancer patients with bone metastasis was 28.6 months, longer than Luminal B (26.9 months), HER-2 overexpression (20.9 months) and triple negative breast cancer patients (12.0 months) with bone metastasis.The overall survival significantly differed among the patients with four subtypes of breast cancer.Conclusion Different subtypes of breast cancer patients with bone metastasis have different clinical characteristics and prognosis.Luminal A breast cancer patients with bone metastasis have better prognosis whereas triple negative subtype has poorer prognosis.

To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%,=1.23, 95%:1.10-1.37,<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,=1.28, 95%:1.04-1.58,<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%,=1.25, 95%:1.12-1.39,<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%,=5.292, 95%:2.933-9.549,<0.01) and mucositis (10.5% vs 2.0%,=5.340, 95%:3.743-7.617,<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all<0.05), while such difference was not found in the occurrence of peripheral neuropathy (>0.05).The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; toxicity ; Bevacizumab ; adverse effects ; therapeutic use ; toxicity ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans ; Neoadjuvant Therapy ; adverse effects ; methods ; Prospective Studies ; Receptor, ErbB-2 ; analysis ; Triple Negative Breast Neoplasms ; drug therapy

Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/Ml, AUC (12 127.39±636.16)ng·h/Ml and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.