The Association between Exposure to Second-Hand Smoke and Disease in the Chinese Population: A Systematic Review and Meta-Analysis / 生物医学与环境科学（英文）

OBJECTIVE@#To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population.@*METHODS@#We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort).@*RESULTS@#In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women.@*CONCLUSION@#The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.

Lung Cancer Risk Attributable to Active Smoking in China: A Systematic Review and Meta-Analysis / 生物医学与环境科学（英文）

OBJECTIVE@#No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population.@*METHODS@#A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking.@*RESULTS@#Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively.@*CONCLUSION@#The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.

The relationship between classroom environment and myopia / 中华流行病学杂志

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m2 was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.

[Expression and Clinical Significance of Long Non-Coding RNA PRAL in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the expression and clinical significance of long non-coding RNA PRAL in patients with multiple myeloma(MM). METHODS: Clinical data of 60 MM patients and 60 healthy people with the same age(as controls) were selected. Real time-quantitative fluorescence PCR (RT-qPCR) was used to determine the expression levels of serum LncRNA PRAL in the patients and controls, and the relationship of its expression with the clinicopathological characteristics and prognosis of patients was analyed. RESULTS: LncRNA PRAL expression in MM patients was significantly lower than that in healthy people (F=13.294, P<0.001). LncRNA PRAL expression correlated with D-S staging and ISS staging in MM patients. PAD efficacy was significantly improved in MM patients with high expression of LncRNA PRAL, and median survival time was significantly prolonged (P<0.05). CONCLUSION: LncRNA PRAL expression decreases in MM patients, while MM patients with high expression of LncRNA PRAL can obtain better therapeutic efficacy and longer survival time.

MicroRNA-22 Suppresses Breast Cancer Cell Growth and Increases Paclitaxel Sensitivity by Targeting NRAS.

In recent study, microRNAs have various important functions in diverse biological processes and progression of cancer. In human breast cancer, microRNA-22 has been reported to be downregulated. However, molecular mechanism of microRNA-22 in breast cancer progression and chemosensitivity has not been well studied. In our study, these results demonstrated that microRNA-22 expression levels were significantly reduced in 40 pairs of human breast cancer tissues when compared to normal tissues. Enforced expression of microRNA-22 inhibited activity of cell proliferation and cell migration in breast cancer cells. Furthermore, microRNA-22 targeted NRAS proto-oncogene, GTPase (NRAS) in breast cancer cells. The expression levels of NRAS in human clinical specimens were higher in breast cancer tissues when compared to normal tissues. Moreover, microRNA-22 sensitized breast cancer cells to paclitaxel by regulation of NRAS. Our results then demonstrated that microRNA-22 functioned as a tumor suppressor microRNA and indicated potential application for the diagnosis and treatment of cancer in the future.

IGF-1-mediated PKM2/ß-catenin/miR-152 regulatory circuit in breast cancer.

Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified ß-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both ß-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting ß-catenin and PKM2 expression. Intriguingly, IGF-1 induced ß-catenin and PKM2 expression and enhanced ß-catenin and PKM2 interaction. Subsequently, IGF-1-induced ß-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, ß-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with ß-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in ß-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.

Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells.

Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway.

Insulin-like growth factor-I induces chemoresistence to docetaxel by inhibiting miR-143 in human prostate cancer.

Elevated levels of insulin-like growth factor-I (IGF-I) are associated with carcinogenesis and cancer progression. However, the molecular mechanisms by which IGF-I promotes prostate cancer development remain to be elucidated. Docetaxel chemotherapy is an important therapeutic strategy in many types of human cancers including prostate cancer. In this study, we showed that IGF-I rendered PC-3 and DU145 cells more resistant to docetaxel treatment. IGF-I treatment decreased miR-143 expression, but increased the expression levels of IGF-I receptor (IGF-IR) and insulin receptor substrate 1 (IRS1), direct targets of miR-143. Overexpression of miR-143 abolished IGF-I-induced chemoresistance to docetaxel treatment, decreased expression levels of IGF-I, IRS1, and vascular endothelial growth factor (VEGF) in prostate cancer cell lines. Furthermore, docetaxel treatment significantly inhibited VEGF transcriptional activation, whereas IGF-I treatment induced VEGF transcriptional activation in a dose-dependent manner. Forced expression of IGF-IR and IRS1 cDNAs without the 3' UTR regions restored miR-143-inhibited VEGF transcriptional activation. Finally, miR-143 inhibited tumor growth and made cells more sensitive to docetaxel treatment for decreasing tumor growth in vivo. Taken together, our data demonstrates that IGF-I induces docetaxel resistance and upregulates IGF-IR and IRS1 expression through miR-143 downregulation, whereas miR-143 acts as a tumor suppressor by targeting its targets IGF-IR and IRS1.

Estrogen regulates miRNA expression: implication of estrogen receptor and miR-124/AKT2 in tumor growth and angiogenesis.

It is currently known that estrogen plays an important role in breast cancer (BC) development, but the underlying molecular mechanism remains to be elucidated. Accumulating evidence has revealed important roles of microRNAs in various kinds of human cancers, including BC. In this study, we found that among the microRNAs regulated by estrogen, miR-124 was the most prominent downregulated miRNA. miR-124 was downregulated by estradiol (E2) treatment in estrogen receptor (ER) positive BC cells, miR-124 overexpression suppressed cell proliferation, migration and invasion in BC cells; while the suppression of miR-124 using Anti-miR-124 inhibitor had opposite cellular functions. Under the E2 treatment, miR-124 had stronger effect to inhibit cellular functions in MCF7 cells than that in MDA-MB-231 cells. In addition, we identified that ERα, but not ERß, was required for E2-induced miR-124 downregulation. Furthermore, AKT2, a known oncogene, was a novel direct target of miR-124. AKT2 expression levels were inversely correlated with miR-124 expression levels in human breast cancer specimens. AKT2 was overexpressed in BC specimens, and its expression levels were much higher in ERα positive cancer tissues than those ERα negative cancer tissues. Consistent with miR-124 suppression, E2 treatment increased AKT2 expression levels in MCF7 cells via ERα. Finally, overexpression of miR-124 in MCF7 cells significantly suppressed tumor growth and angiogenesis by targeting AKT2. Our results provide a mechanistic insight into a functional role of new ERα/miR-124/AKT2 signaling pathway in BC development. miR-124 and AKT2 may be used as biomarkers for ERα positive BC and therapeutic effect in the future.

An oncogenic kinase: putting PAK5 forward.

INTRODUCTION: Overexpression of p21-activated kinase 5 (PAK5) is discovered in many tumors, probably due to its regulation in cytoskeleton, antiapoptosis and proliferation. A better understanding of the modulation mechanisms of PAK5 is needed for the development of tumor treatment where current therapeutics is inadequate. AREAS COVERED: This review discusses the current understanding of PAK5 functions as an oncogenic kinase in tumor cellular regulation. Mechanisms of action and molecular pathways involved in cytoskeleton regulation, antiapoptosis and proliferation of tumors are discussed. EXPERT OPINION: PAKs are serine/threonine kinases and downstream effectors for Cdc42 and Rac, the subfamilies of Rho small GTPases. PAK5 shares sequence identities in p21-GTPase-binding domain and kinase domain and is completely different in other regions compared with other PAKs. Overexpression of PAK5 has been found in several tumors, probably due to its contribution to proliferation, cytoskeleton and anti-apoptosis. Additional regulation mechanisms which are independent of Rho GTPases also indicate that PAK5 functions as a special signal molecule in cellular signaling pathways of tumor progression.

Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway.

PAK5 (p21 activated kinase 5) is upregulated in human colorectal carcinoma cells and is a known tumor promoter in carcinogenesis of the colon. Little is known regarding the mechanisms underlying the downstream targets of PAK5, and information concerning its biological significance in glioma is lacking. In this study, we investigated the effects of PAK5 on proliferation, migration, invasion, and apoptosis in human U87 and U251 glioma cells and examined the underlying molecular mechanism. We performed cell growth assays and cell cycle analysis to observe the cell proliferation. Flow cytometry analysis was performed to evaluate apoptosis, and in vitro scratch assays, cell migration assays, and gelatin zymography were performed to examine cell migration. Western blot analysis was performed to examine signal transduction in the cells. We demonstrated that suppression of PAK5 in glioma cells significantly inhibited cell migration and invasion. We also observed that suppression of PAK5 in human glioma cell lines inhibited cell growth because of G1 phase arrest. Additionally, flow cytometry and Western blot analysis indicated that PAK5 could inhibit cell apoptosis. These results suggest that the PAK5-Egr1-MMP2 signaling pathway is involved in tumor progression and may have a potential role in cancer prevention and treatment.

p21-Activated kinase 5: a pleiotropic kinase.

The PAKs (p21-activated kinases) are highly conserved serine/threonine protein kinases which comprise six mammalian PAKs. PAK5 (p21-activated kinase 5) is the least understood member of PAKs that regulate many intracellular processes when they are stimulated by activated forms of the small GTPases Cdc42 and Rac. PAK5 takes an important part in multiple signal pathways in mammalian cells and controls a variety of cellular functions including cytoskeleton organization, cell motility and apoptosis. The main goal of this review is to describe the structure, mechanisms underlying its activity regulation, its role in apoptosis and the likely directions of further research.

Study on the tumor infiltration in mesorectum of rectal cancer by spiral computed tomography and histopathology / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of spiral computed tomography in the preoperative assessment of the degree of tumor infiltration in mesorectum and circumferential resection margin status of rectal cancer compared with large tissue slice technique.</p><p><b>METHODS</b>Fifty-seven patients with rectal cancer diagnosed by fiber colonoscopy and pathology from March 2007 to December 2007 underwent preoperative 64-layers spiral CT examination. The degree of tumor infiltration in mesorectum and circumferential resection margin status were evaluated. Large tissue slice technique was applied in the pathologic study after the total mesorectal excision of the rectum to determine the degree of tumor infiltration in mesorectum and the circumferential resection margin status. The spiral CT findings were compared with pathologic results. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the CT results were assessed respectively.</p><p><b>RESULTS</b>The overall spiral CT accuracy was 93.0% (53/57) for the degree of tumor infiltration in mesorectum, and it was 94.7%, 94.7% and 96.5% for degree I, II, III infiltration, respectively. Fifty-three cases (93.0%) were accurately predicated with the circumferential resection margin status. The sensitivity, specificity, PPV and NPV of spiral CT measurement was 80.0%, 97.6%, 92.3% and 93.2%, respectively, and was consistent well with the histopathological diagnosis.</p><p><b>CONCLUSIONS</b>Spiral CT provides accurate preoperative assessment for the degree of tumor infiltration in mesorectum and circumferential resection margin status of rectal cancer.</p>

In vitro differentiaion of peripheral blood mononuclear cells into smooth muscle progenitor cells / 上海第二医科大学学报

Objective To optimize methods of culturing smooth muscle progenitor cells(SPCs) from mononuclear cells(MNCs) of peripheral blood. Methods Human MNCs isolated from buffy coat were seeded on M-199 with bovine pituitary extraction.On the eighth day outgrowth cells were stimulated with platelet-derived growth factor-BB(PDGF-BB).Fifteen days later,immunofluorescence,Western blot or RT-PCR was used to analyzed the expression of smooth muscle cell specific ?-actin(?-SMA),smooth muscle myosin heavy chain(SM MHC),Calponin,CD34,Tie-2 and Flk-1,and fluorescence activated cell sorter was employed to examine ?-SMA positive cells ratio. Results The cells stimulated by PDGF-BB for 15 d were positive for ?-SMA,SM MHC,Calponin,CD34 and Flk-1,but negative for Tie-2.The ?-SMA positive cells ratio was(90.57?5.63)%,significantly different from that of the control(P