The microclimate impact of treetop walk based on plant community simulation.

The treetop walk is an innovative urban greenway that harmoniously integrates with the natural topography, meandering through the tree canopy. It serves as a vital element in elevating the urban mountain landscape while also significantly impacting the recreational experiences of the public through its microclimate effects. Moreover, the distinctive plant community characteristics of the treetop walk significantly enhance the microclimate. Examining the plant community attributes that potentially influence the microclimate conditions of the treetop walk is of utmost importance. We chose the Fu Forest Trail in Fuzhou as the sample site for this research. By implementing an orthogonal experimental design and using ENVI-met software, we simulated data to explore the impacts of various plant community characteristics on the microclimate of the treetop walk in autumn. The findings revealed the following results: (1) The presence of tree height, leaf area index, crown type, and planting density significantly influenced the microclimate of the treetop walk green spaces, with some factors having primary effects while others having secondary effects. (2) No significant variations were observed in the microclimate effects of diverse plant community characteristics in the treetop walk during morning, noon, and evening hours. (3) Scheme 13 emerged as the optimal choice for cooling and humidifying ventilating, characterized by a tree height of 20 m, leaf area index of 4.4, spherical crown shape, and planting spacing of 2 m. The tree species available in the Fuzhou area include Ligustrum quihoui Carr., Buxus sinica, Laurus nobilis, Myrica rubra, and Osmanthus fragrans. (4) Compared to traditional understory trails, tree height and planting spacing notably influence the microclimate environment of the treetop walk.

Progress and evolution of hotspots in butterfly diversity research in green spaces.

Ecosystems depend on biodiversity; therefore, protecting biodiversity is beneficial for the development of ecosystems. Butterflies are indicator species that respond quickly to environmental changes and reflect environmental conditions. Butterfly diversity is a crucial evaluation indicator of habitat quality in green spaces. We used CiteSpace and Bibliometrix to conduct a bibliometric analysis of research relating to butterfly diversity in green spaces. Based on 538 papers published from 2002-2022, we systematically reviewed the status, frontiers, and hotspots for research on butterfly diversity in green spaces. Our results showed that: (1) Research on butterfly diversity in green spaces has consistently demonstrated an upward trend between 2002-2022. Studies on this subject have garnered attention from researchers worldwide, with notable interest and contributions from scholars in the United States. (2) Early studies focused on butterfly habitat preferences and extinction concerns, and later articles appeared on the influence of external environmental factors (land use, climate change, plants, etc.). (3) Three main research topics received much attention between 2002 and 2022: biodiversity conservation, butterfly habitats, and the relationship between butterfly diversity and its influencing factors. (4) The relationship between green spaces and butterfly diversity (landscape features, vegetation features, and human activities) was discussed; these factors on butterfly communities should be considered in the planning and constructing of future green spaces. (5) Two significant future directions have been identified: more research on the impact of external factors and a need for more technical integration with the big data field. Future research on butterfly diversity in green spaces should adopt a more multi-scale, multi-disciplinary approach and aim to enhance the practicality and guidance of research findings.

Risk effects of meteorological factors on human brucellosis in Jilin province, China, 2005-2019.

Background: The impact of climate on zoonotic infectious diseases (or can be referred to as climate-sensitive zoonotic diseases) is confirmed. Yet, research on the association between brucellosis and climate is limited. We aim to understand the impact of meteorological factors on the risk of brucellosis, especially in northeastern China. Methods: Monthly incidence data for brucellosis from 2005 to 2019 in Jilin province was obtained from the China Information System for Disease Control and Prevention (CDC). Monthly meteorological data (average temperature (°C), wind velocity (m/s), relative humidity (%), sunshine hours (h), air pressure (hPa), and rainfall (mm)) in Jilin province, China, from 2005 to 2019 were collected from the China Meteorological Information Center (http://data.cma.cn/). The Spearman's correlation was used to choose among the several meteorological variables. A distributed lag non-linear model (DLNM) was used to estimate the lag and non-linearity effect of meteorological factors on the risk of brucellosis. Results: A total of 24,921 cases of human brucellosis were reported in Jilin province from 2005 to 2019, with the peak epidemic period from April to June. Low temperature and low sunshine hours were protective factors for the brucellosis, where the minimum RR values were 0.50 (95 % CI = 0.31-0.82) for -13.7 °C with 1 month lag and 0.61 (95 % CI = 0.41-0.91) for 110.5h with 2 months lag, respectively. High temperature, high sunshine hours, and low wind velocity were risk factors for brucellosis. The maximum RR values were 2.91 (95 % CI = 1.43-5.92, lag = 1, 25.7 °C), 1.85 (95 % CI = 1.23-2.80, lag = 2, 332.6h), and 1.68 (95 % CI = 1.25-2.26, lag = 2, 1.4 m/s). The trends in the impact of extreme temperature and extreme sunshine hours on the transmission of brucellosis were generally consistent. Conclusion: High temperature, high sunshine hours, and low wind velocity are more conducive to the transmission of brucellosis with an obvious lag effect. The results will deepen the understanding of the relationship between climate and brucellosis and provide a reference for formulating relevant public health policies.

MicroRNA-19a targets tissue factor to inhibit colon cancer cells migration and invasion.

The over-expression of tissue factor (TF) and its roles in colon cancer progression have attracted much attention. However, the mechanisms regulating TF expression have not yet been shown in detail. In this study, we over-expressed miR-19a, miR20a and miR-106b in colon cancer cells, and evaluated their impact on TF expression and cellular function. We provide evidence demonstrating that miR-19a inhibited TF expression in vitro. Luciferase reporter assay confirmed that TF was a direct target of miR-19a because the miR-19a mediated repression of luciferase activity was abolished by mutation of the putative binding site. Moreover, miR-19a suppressed colon cancer cell migration and invasion. This effect was due to the indirect down-regulation of matrix metalloproteinase 9. Finally, we investigated the relevance of TF and miR-19a expression in a total of 48 paired colon cancer samples and revealed that miR-19a was inversely correlated with TF expression in stages I and II cases. Therefore, our results suggested that miR-19a was capable of suppressing TF expression in vitro and inhibiting cell migration and invasion. Although it was not the unique mechanism responsible for the expression of TF in vivo, miR-19a was inversely correlated with TF expression in early stage colon cancer patients.

Strategies for Cartilage Repair in Osteoarthritis Based on Diverse Mesenchymal Stem Cells-Derived Extracellular Vesicles.

Osteoarthritis (OA) causes disability and significant economic and social burden. Cartilage injury is one of the main pathological features of OA, and is often manifested by excessive chondrocyte death, inflammatory response, abnormal bone metabolism, imbalance of extracellular matrix (ECM) metabolism, and abnormal vascular or nerve growth. Regrettably, due to the avascular nature of cartilage, its capacity to repair is notably limited. Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) play a pivotal role in intercellular communication, presenting promising potential not only as early diagnostic biomarkers in OA but also as efficacious therapeutic strategy. MSCs-EVs were confirmed to play a therapeutic role in the pathological process of cartilage injury mentioned above. This paper comprehensively provides the functions and mechanisms of MSCs-EVs in cartilage repair.

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review.

Osteoarthritis (OA) causes pain and disability in the elderly and has placed a severe burden on healthcare worldwide. Excessive death and decreased density of chondrocytes are recognized as the major pathological characteristic of OA. Chondrocytes have been shown to have multiple forms of death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. The excessive death of chondrocytes often forms a vicious circle with imbalanced chondrocytes extracellular matrix (ECM) metabolism. Therefore, inhibiting chondrocytes excessive death has become a key point that cannot be ignored in the development of OA treatment strategies. We summarized recent studies on the functions and mechanisms of different modes of chondrocyte death and potential therapeutic strategies for OA and offered our views. This may provide direction and theoretical support for formulating OA treatment strategies in the future.

Butterfly Communities Vary under Different Urbanization Types in City Parks.

Butterflies are key indicators of urban biodiversity and one of the most vulnerable organism groups to environmental changes. Studying how butterflies are distributed and what factors might influence them in urban green spaces is crucial. In this study, from July 2022 to September 2022, we examined and analyzed the butterfly diversity in nine parks in Fuzhou, China, along three different levels of urbanization (urban, peri-urban, and suburban). We investigated how butterfly communities respond to increasing urbanization. The findings revealed that: (1) A total of 427 butterfly individuals from 4 families and 13 species were observed; (2) Shannon diversity, richness, and abundance of the overall butterfly community were lower in the more urbanized parks. Urbanization had significant effects on Shannon diversity (p = 0.003) and abundance (p = 0.007) but no significant effects on the whole butterfly community richness (p = 0.241); (3) non-metric multidimensional scaling revealed that there were differences in the overall number of butterfly species in urban parks among different geographic regions.

The Impact of Urbanization on Taxonomic Diversity and Functional Similarity among Butterfly Communities in Waterfront Green Spaces.

Urbanization has been shown to cause biodiversity loss. However, its effects on butterfly taxonomic and functional diversity still need to be studied, especially in urban waterfront green spaces where mechanisms of impact still need to be explored. We used butterflies as indicators to study how urbanization affects their taxonomic and functional diversity and identify indicator species in different urban ecological gradient areas. From July to September 2022, we surveyed 10 urban waterfront green spaces in Fuzhou City, China. We recorded 1163 butterflies of 28 species from 6 families. First, we explored the effects of urbanization on butterfly communities and made pairwise comparisons of different urban ecological gradients (α-diversity); secondly, we looked for differences between butterfly communities across urban ecological gradients (ß-diversity); finally, we investigated differences in the response of butterfly functional groups to different urban ecological gradient areas and identified ecological indicative species. This study found the following: (1) Urbanization has led to the simplification of butterfly community structure, but there are also favorable factors that support the survival of individual butterflies; (2) Urbanization has led to significant differences in butterfly communities and plant-feeding polyphagous butterfly groups; (3) Urbanization has led to differences in the functional diversity of butterfly diet and activity space groups; (4) We identified five eco-indicator species in different urban ecological gradients.

Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis.

BACKGROUND: The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis. METHODS: We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes. RESULTS: The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter's test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results. CONCLUSIONS: In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

Association between meteorological factors and varicella incidence: a multicity study in Yunnan Province, China.

This multicenter study aimed to investigate the relationship between varicella incidence and meteorological factors including mean temperature, relative humidity, sunshine duration, diurnal temperature difference, wind speed, and rainfall, as previous studies have produced varying results. Our study also sought to identify potential sources of heterogeneity. Data on reported daily varicella numbers and meteorological factors were collected for 14 cities in Yunnan Province from 2017 to 2021. A distribution-lagged nonlinear model was constructed to explore the relationship between meteorological conditions and varicella incidence in each included city. We then used multiple meta-regression to explore sources of heterogeneity using demographic economics indicators, air pollutants, and geographic location as potential modifiers. The cumulative hazard effect plot showed an inverted S-shape for the relationship between temperature and varicella, with the smallest RR (relative risk) (0.533, 95% CI: 0.401-0.708) at temperatures up to 27.2 °C. The maximum RR (1.171, 95% CI: 1.001-1.371) was obtained when the relative humidity was equal to 98.5%. The RR (1.164, 95% CI: 1.002-1.352) was greatest at a diurnal temperature range of 2 °C (1.164, 95% CI: 1.002-1.352) and least (0.913, 95% CI: 0.834-0.999) at a diurnal temperature range of 16.1 °C. The maximum RR (1.214, 95% CI: 1.089-1.354) was obtained at 0 h of sunshine, and the minimum RR (0.808, 95% CI: 0.675-0.968) was obtained at 12.4 h of sunshine. The RR (0.792, 95% CI: 0.633-0.992) was minimum at a wind velocity of 4.8 m/s. Residual heterogeneity ranged from 1 to 42.7%, with PM10 (particles with an aerodynamic diameter less than 10 µm), GDP (gross domestic product), and population density explaining some of this heterogeneity. The temperature has a dual effect on varicella incidence. Varicella cases are negatively correlated with diurnal temperature range, sunshine duration, and wind speed, and positively correlated with relative humidity. GDP and PM10 may have a significant role in altering the association between temperature and varicella, while PM10 and population density may alter the association between wind velocity and varicella.

Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer.

BACKGROUND: MicroRNAs have been shown to offer great potential in both the diagnosis and prognosis of cancer. Despite the well-established role of the miR-17-92 in cancer formation and progression, the contribution of each individual miRNA remains to be characterized. Thus, we investigated whether deregulation of the miR-17-92 associated with colon cancer prognosis. METHODS: Expression levels of the miR-17-92 cluster and its paralogs were determined in 48 colon tumor and 48 paired normal tissues by real-time qRT-PCR. Associations with miRNA expression, age, sex, TNM staging, and survival prognosis were evaluated. RESULTS: MiR-17-92 cluster and its paralogs were significantly overexpressed in colon tumor. No significant associations were found between the deregulation of certain miRNAs and the clinical and pathologic characteristics observed in patients. Kaplan-Meier curves demonstrated significantly reduced overall survival in patients expressing high levels of miR-17. In multivariate Cox models, miR-17 overexpression (HR 2.67; P = 0.007) and TNM staging (HR 8.87; P = 0.002) were significantly associated with a risk of death. CONCLUSIONS: The miR-17-92 cluster and its paralogs were significantly elevated in patients with colon cancer, and heightened expression of miR-17 was associated with poor survival. Moreover, miR-17 and TNM staging were both identified as significant, but independent, prognostic biomarkers in colon cancer.

Quantitative and chemical fingerprint analysis for the quality evaluation of Isatis indigotica based on ultra-performance liquid chromatography with photodiode array detector combined with chemometric methods.

A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.

[Primary safety evaluation of sulfated paeoniae radix alba].

The paper is to report the development of a method of quantitative analysis of multi-components by high performance liquid chromatography (HPLC) for simultaneously determining paeoniflorin sulfonate (PS), paeoniflorin (PF) and albiflorin (AF) in sulfated Paeoniae Radix Alba. Moreover, the cytotoxicity of paeoniflorin sulfonate by MTT-assay and the acute toxicity of mice by administration of paeoniflorin sulfonate were evaluated. Chromatographic separation of paeoniflorin sulfonate, PF and AF were performed on a SHISEIDO CAPCELL PAK C18 column (250 mm x 4.6 mm, 5 microm) for HPLC and a mixture of acetonitrile and 0.02% phosphoric acid solution (15 : 85) as the mobile phase. As detector a spectrophotometer set at 230 nm; column temperature 30 degrees C; flow rate 1.0 mL x min(-1). The toxicity of paeoniflorin sulfonate was evaluated by in vitro cytotoxicity carried out on mouse and human primary hepatocytes, and by acute oral toxicity test carried out on mice. The calibration curve of paeoniflorin sulfonate, PF and AF revealed linearity in the range of 0.041 8 - 1.045 0, 0.023 5 - 0.587 5, and 0.039 8 - 0.995 0 mg x mL(-1), respectively (r > 0.999 8). The average recovery was ranged from 99.11% to 101.71%, RSD < 2%. Paeoniflorin sulfonate does not have any cytotoxicity to cells at all the tested concentrations (< or = 300 micromol x L(-1)) in the in vitro cytotoxicity assay. The maximum tolerance dose of paeoniflorin sulfonate solution and extraction of Paeoniae Radix Alba to mouse is 5 g x kg(-1) and 80 g x kg(-1) respectively. The contents of these three components in the samples were determined with the developed method. It is a rapid, convenient and accurate method to determine multi-components. The content of PF in sulfated Paeoniae Radix Alba is significantly lower, and there is negative correlationship between the content of paeoniflorin sulfonate and PF. The in vitro cytotoxicity assay and in vivo mouse acute toxicity test showed that there is no obvious toxicity of paeoniflorin sulfonate and water-soluble extract of sulfated Paeoniae Radix Alba.

[Analysis of prognostic factors in patients with lymph node-negative rectal cancer].

OBJECTIVE: To investigate the risk factors for the prognosis in patients with node-negative rectal cancer. METHODS: Clinicopathological characteristics of 117 patients with lymph node-negative rectal carcinoma undergoing curative rectectomy from January 2005 to December 2008 were retrospectively analyzed. RESULTS: The overall 5-year survival rate was 91.5%. The univariate analysis revealed that tumor size(χ(2)=8.422,P=0.004), invasive depth(T staging, χ(2)=9.448,P=0.024), cell differentiation(χ(2)=26.571,P=0.000), pathologic type(χ(2)=4.712,P=0.030) and preoperative level of carcinoembryonic antigen(χ(2)=4.131,P=0.042) had significant effects on the survival. In multivariate analysis, the independent prognostic factors for these patients were tumor size (Wald=5.286,P=0.022), cell differentiation (Wald=7.172, P=0.007) and invasive depth (T staging, Wald=5.741, P=0.017). CONCLUSION: For node-negative rectal cancer patients, tumor size, poor differentiation and invasive depth are important markers to evaluate their prognosis.

[Characteristic chromatographic profile of Paeoniae Radix and its application in quality control of crude and processed drugs of different origins and processing methods].

OBJECTIVE: To establish a HPLC method of characteristic chromatographic profile for the quality control of Paeoniae Radix. METHOD: The 67 batches of samples were analyzed on a Polaris C18-A column with a gradient elution of acetonitrile and phosphate solution (pH 3.0) at a flow rate of 1.0 mL x min(-1) and detected at 230 nm. RESULT: Nine main marker peaks were identified and semi-quantificated. By the similarity evaluation software for chromatographic fingerprint of traditional Chinese medicine (Version 2004A) and hierarchical clustering analysis, 67 batches of Paeoniae Radix were classified. CONCLUSION: The method can be applied for quality assessment of Paeoniae Radix.

[Simultaneous assay of paeoniflorin and albiflorin in Paeoniae Radix Alba by QAMS].

OBJECTIVE: To develop a method of quantitative analysis of multi-components by single marker (QAMS) for simultaneously determining paeoniflorin and albiflorin in Paeoniae Radix Alba. METHOD: Using paeoniflorin as the internal reference substance, the relative correction factor (RCF) of albiflorin was determined by HPLC and UPLC with good reproducibility. The contents of paeoniflorin in 16 samples of Paeoniae Radix Alba were authentically determined by the external standard method, and the content of albiflorin was calculated according to the RCF. The contents of these two components in the samples were determined with the external standard method. RESULT: No siginificant differences between the quantitative results of QAMS method and external standard method were observe. CONCLUSION: It is a convenient and accurate method to determine multi-components when some authentic standard substances were unavailable. It can be used to control the quality of Paeoniae Radix Alba

P2X7 Receptor Deficiency Ameliorates STZ-induced Cardiac Damage and Remodeling Through PKCß and ERK.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus which result in cardiac remodeling and subsequent heart failure. However, the role of P2X7 receptor (P2X7R) in DCM has yet to be elucidated. The principal objective of this study was to investigate whether P2X7R participates in the pathogenesis of DCM. In this study, the C57BL/6 diabetic mouse model was treated with a P2X7R inhibitor (A438079). Cardiac dysfunction and remodeling were attenuated by the intraperitoneal injection of A438079 or P2X7R deficiency. In vitro, A438079 reduced high glucose (HG) induced cell damage in H9c2 cells and primary rat cardiomyocytes. Furthermore, HG/streptozotocin (STZ)-induced P2X7R activation mediated downstream protein kinase C-ß (PKCß) and extracellular regulated protein kinases (ERK) activation. This study provided evidence that P2X7R plays an important role in the pathogenesis of STZ-induced diabetic cardiac damage and remodeling through the PKCß/ERK axis and suggested that P2X7R might be a potential target in the treatment of diabetic cardiomyopathy.

Suppression of Netrin-1 attenuates angiotension II-induced cardiac remodeling through the PKC/MAPK signaling pathway.

BACKGROUND: Myocardial remodeling caused by angiotensin II (Ang II) is essential for the pathological process of heart failure. Netrin-1, which is an axonal guidance cue, has been shown to be involved in the inflammatory response, tumorigenesis, and angiogenesis in non-neuronal tissues. However, the role of Netrin-1 in cardiac remodeling has not been fully elucidated. METHODS: The rat cardiomyocyte cell line H9c2 and primary neonatal rat cardiomyocytes were treated with Ang II. Cells were transfected with siRNA to silence Netrin-1 expression. Real-time polymerase chain reaction and Western blot analysis were used to detect the markers for fibrosis, apoptosis, and hypertrophy in cardiomyocytes. An Annexin V-EGFP/PI cell apoptosis detection kit was used to measure the level of apoptosis caused by angiotensin II. RESULTS: We found that Netrin-1 expression was upregulated in the H9c2 cells and the neonatal rat cardiomyocytes stimulated by Ang II. The increased Netrin-1 expression was decreased by valsartan to block AT1R. Importantly, the application of Netrin-1 siRNA significantly alleviated the degrees of myocardial hypertrophy, fibrosis (reflected by Myhc, collagen I, and TGF-ß) and apoptosis (reflected by the level of Caspase 3, Bax, and Bcl-2) induced by Ang II. In addition, the silencing of Netrin-1 substantially decreased the phosphorylation of PKCα, JNK, and P38. We treated H9c2 cells with LY317615, SP600125, and SB203580, inhibitors of PKCα, JNK, and P38, respectively, thereby resulting in a substantial decrease in hypertrophy, fibrosis, and apoptosis. CONCLUSIONS: Ang II produces cardiac hypertrophy, fibrosis, and apoptosis through the upregulation of Netrin-1 and the activation of the AT1R/PKCα/MAPK (JNK, P38) pathway. Suppression of Netrin-1 can relieve Ang II-induced cardiac remodeling via inhibition of the PKCα/MAPK (JNK and P38) signaling pathway. Thus, Netrin-1 may be a novel therapeutic target for Ang II-mediated cardiac remodeling.

[Efficacy analysis of neoadjuvant chemoradiotherapy combined with total pelvic exenteration in the treatment of primary T4b rectal cancer].

OBJECTIVE: To investigate the value of neoadjuvant chemoradiotherapy (nCRT) combined with total pelvic exenteration (TPE) in the treatment of primary T4b rectal cancer. METHODS: A retrospective cohort study was conducted to analyze the clinicopathological data of 31 patients with primary T4b rectal cancer who underwent TPE from January 2008 to December 2015 at Peking University First Hospital. INCLUSION CRITERIA: preoperative clinical stage (cTNM) was defined as cT4b primary rectal cancer with only front wall Invasion; the lower edge of tumor was within 10 cm from the anal margin; TPE was performed; R0 resection was confirmed by pathology. Patients with recurrent rectal cancer, distant metastasis, and undergoing TPE for non-rectal tumors were excluded. Patients were divided into nCRT group and non-nCRT group according to whether receiving nCRT before surgery. The nCRT group received long course radiotherapy (total dose 50 Gy in 25 daily fractions) with concomitant chemotherapy (Capecitabine), and the surgery was performed 6-8 weeks after the neoadjuvant chemoradiation, while the non-nCRT group received surgery directly. The intraoperative, postoperative and pathological conditions and local recurrence were compared between the two groups. The survival curves were drawn by Kaplan-Meier method and the survival of two groups were compared. RESULTS: A total of 31 patients were enrolled, including 13 patients in the nCRT group and 18 patients in the non-nCRT group. The baseline data, such as age, duration of disease, preoperative basic disease, body mass index, smoking rate, and tumor distance from the anal margin, were not significantly different between the two groups (all P>0.05). In the nCRT group and non-nCRT group respectively, the ratio of anal preservation was 30.8%(4/13) and 38.9%(7/18) (P=0.468), the median intraoperative blood loss was 1 000 ml and 800 ml (P=0.644), the operation time was (531.7±137.2) minutes and (498.0±90.1) minutes (P=0.703), the median hospital stay was 18 days and 14 days (P=0.400), the morbidity of complications within 30 days after surgery was 23.1%(3/13) and 38.9%(7/18)(P=0.452), the incidence of postoperative abdominal abscess was 15.4%(2/13) and 0 (P=0.168), the proportion of secondary surgery was 7.7%(1/13) and 11.1%(2/18)(P=1.000), whose differences were not significantly different. The proportion of postoperative pathological pT4b in whole group was 58.1%(18/31), including 53.8%(7/13) in nCRT group and 61.1%(11/18) in non-nCRT group, which was not significantly different between the two groups (P=0.691). The number of harvested lymph node in nCRT group was 13.5±5.9, which was significantly less than 23.0±11.8 in non-nCRT group (P=0.013). There was no pathological complete remission (ypCR) case in nCRT group, and among 13 patients, tumor regression grade (TRG) of 2, 3, 4, and 5 was in 1 case (7.7%), 6 cases (46.2%), 5 cases(38.5%), and 1 case (7.7%), respectively. The median follow-up time was 33 (2 to 115) months, and the follow-up rate was 93.5%(29/31). One case was lost in both the nCRT group and non-nCRT group. The 3-year disease-free survival rate was 43.5% in pooled data, and was 43.6% and 43.3% in nCRT group and non-CRT group respectively without significant difference (P=0.833). The 3-year overall survival rate was 51.1% in pooled data, and was 45.7% and 54.7% in nCRT group and non-nCRT group respectively without significant difference (P=0.653).The local recurrence rate of nCRT and non-nCRT groups was 8.3%(1/12) and 5.9%(1/17) respectively, and the distant metastasis rate was 50.0%(6/12) and 41.2%(7/17) respectively, whose differences were not statistically significant as well (P=1.000 and P=0.865, respectively). CONCLUSION: For primary T4b rectal cancer which can achieve R0 resection through total pelvic exenteration, neoadjuvant chemoradiotherapy has not been demonstrated any advantage in tumor regression, reducing local recurrence, or improving survival, and may increase postoperative complications.

P2X7 receptor regulates EMMPRIN and MMP­9 expression through AMPK/MAPK signaling in PMA­induced macrophages.

The rupture of atherosclerotic plaques may result in the formation of thrombi, which may induce subsequent cardiac events such as acute myocardial infarction. Overproduction of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducers (EMMPRINs) by monocytes and macrophages may lead to rupture of atherosclerotic plaques as a result of the degradation of the extracellular matrix. The purinergic 2X7 receptor (P2X7R) is expressed in macrophages that are assembled in atherosclerotic lesions of human carotid arteries. P2X7R may serve a crucial role in the development of atherosclerosis; therefore, the present study aimed to determine whether P2X7R regulated the expression of EMMPRIN and MMP­9 in phorbol 12­myristate 13­acetate (PMA)­induced macrophages. In addition, the potential molecular mechanisms involved in this process were investigated. THP­1 human monocytic cells were pretreated with A­438079 (a specific inhibitor of P2X7R) for 1 h and subsequently incubated with or without PMA for 48 h. Exposure to A­438079 significantly decreased the expression of MMP­9 and EMMPRIN in the PMA­induced macrophages and attenuated the activation (phosphorylation) of mitogen­activated protein kinase (MAPK) signaling, including c­Jun N­terminal kinase, p38 and extracellular signal­regulated kinase. The present study also demonstrated that 5'­AMP­activated protein kinase (AMPK) was activated by PMA exposure during differentiation from monocytes to macrophages. This activation was reversed by A­438079 treatment through the inhibition of P2X7R expression. These results suggested that the inhibition of P2X7R may be able to suppress the AMPK/MAPK signaling pathway and consequently downregulate both EMMPRIN and MMP­9 expression in PMA­induced macrophages.