Factors Influencing the Fasting Time in Adult Patients After the Endoscopic Management of Sharp Esophageal Foreign Bodies.

Background: Sharp esophageal foreign body (SEFB) impaction can cause varying degrees of damage to the esophagus. There are few studies analyzing the postoperative fasting time in SEFB patients. Methods: We retrospectively collected 835 SEFB patients. According to the fasting time after the endoscopic removal (ER) of SEFBs, the patients were divided into two groups: short fasting time (SFT, fasted ≤24 h) and long fasting time (LFT, fasted >24 h). Results: There were 216 and 619 patients in the SFT and LFT group, respectively. The average age of the SFT group (52.97 years) was younger than that of the LFT group (55.96 years) (p = 0.025). The LFT group had lower proportion of duration of impaction (DOI) within 12 hours (14.2% vs 22.2%, p = 0.006) and erosion rates (89.0% vs 94.0%, p = 0.034) as well as higher proportion of esophageal perforation (19.5 vs 6.5%, p = 0.010) and patients who got intravenous anesthesia (63.78% vs 31.9%, p = 0.000) than the SFT group. The longest diameter of the foreign body (Lmax) in the LFT group (2.60 ± 1.01 cm) was greater than that in the SFT group (2.41 ± 0.83 cm; p = 0.01). Multivariate regression analysis found that age (OR = 1.726[1.208-2.465], p = 0.003), DOI (OR = 1.793[1.175-2.737], p = 0.007), Lmax (OR = 1.477[1.033-2.111], p = 0.032), perforation (OR = 3.698[2.038-6.710]; p < 0.01) and intravenous anesthesia (OR = 3.734[2.642-5.278]; p < 0.01) were the independent factors that prolonged fasting time in patients with SEFBs, while esophageal mucosal erosion (OR = 0.433[0.229-0.820]; p = 0.01) was the influencing factor leading to shortened fasting time. Conclusion: For the first time, we analyzed factors influencing the fasting time after ER in SEFB patients. Age, DOI, Lmax, perforation and intravenous anesthesia were risk factors for a prolonged postoperative fasting time.

[Sensitivity Analysis of Ozone Formation Using Response Surface Methodology].

Identifying the nonlinear relationship between O3 and its precursors accurately plays an important role for the policy-making of O3 pollution control. In this study, the response surface methodology based on the box model simulation was used to quickly and efficiently quantify the O3 response to their precursors with the optimal experimental design. The results showed that CO had a positive contribution to ozone generation, whereas NOx and VOCs had a significant nonlinear relationship with O3. When the ratio of φ(VOCs) to[φ(NOx)-13.75] was greater than 4.17, the ozone formation regime was NOx-limited and became VOCs-limited when the ratio was less than 4.17. Olefin was the key VOCs' component to affect the formation of O3; when the radio of φ(olefin) to[φ(NOx)-15] was less than 1.10 and the value of the φ(olefin) was less than 35×10-9, olefin went far towards generating O3. Response surface methodology demonstrated that it can be well used to explore the influence of multiple factors and their interactions on O3 formation and provides a new approach for efficient O3 sensitivity analysis.

Case report and literature review: Isolated HCC- recurrence in gallbladder after curative resection.

Background: Liver resection (LR) is considered the mainstay treatment for eligible patients with hepatocellular carcinoma (HCC) and provides a 5-year overall survival (OS) of 60%-80%. However, the recurrence rate within five years after LR remains high, ranging from 40% to 70%. Recurrence in gallbladder after liver resection is extremely rare. Here, we present a case of isolated recurrence in gallbladder after curative resection of HCC and review the relevant literature. No similar cases have been reported before. Case presentation: A 55-year-old male patient was diagnosed with HCC in 2009 and subsequently underwent a right posterior sectionectomy of the liver. In 2015, the patient underwent liver tumor radiofrequency ablation and three transarterial chemoembolization (TACE) procedures in succession for HCC recurrence. In 2019, a gallbladder lesion was detected by computed tomography (CT) without perceivable intrahepatic focus. We performed an en bloc resection of the gallbladder and hepatic segment IVb. The pathological biopsy suggested that the gallbladder tumor was moderately differentiated HCC. The patient survived more than 3 years in good condition, and there were no signs of tumor recurrence. Conclusions: In patients with isolated gallbladder metastasis, if the lesion can be resected en bloc without remnants, surgery should be the preferred option. Both postoperative molecularly targeted drugs and immunotherapy are expected to improve the long-term prognosis.

[Establishment of High-Resolution Emissions Inventory in Wuhai and Its Application in Exploring the Causes of Ozone Pollution].

Wuhai is a typical coking industrial base including three industrial parks within its jurisdiction. The emission amount of air pollutants is considerable here, and O3 pollution has become serious in recent years. Clarifying the air pollutant emission characteristics and exploring the formation mechanism of O3 are the basis for objectively understanding the O3 pollution and formulating scientific prevention and control measures. This study established the high-resolution emission inventory of Wuhai in 2018 (HEI-WH18) based on the "coefficient method," evaluated the applicability and accuracy of HEI-WH18 using the WRF-Chem model, and explored the causes of O3 pollution in summer using WRF-Chem diagnosis module output. The HEI-WH18 showed that the total emissions amount of SO2, NOx, CO, PM10, PM2.5, VOCs, NH3, BC, and OC were 65943, 40934, 172867, 159771, 47469, 69191, 1407, 1491, and 1648 t·a-1, respectively. HEI-WH18 could capture the variation and magnitude of O3 and its precursors better than the MEIC, which was suitable for the O3 simulation and source analysis in summer. From the perspective of spatial distribution, Haibowan was a high-value area of O3 during the daytime, and the three industrial parks were low-value areas of O3 and high-value areas of NO2 during the daytime and nighttime. The spatial distribution characteristics of CO were consistent with the spontaneous combustion of coal and coal gangue sources. According to the diagnostic analysis of two O3 pollution processes, the O3 increase in the upper boundary layer was mainly related to the advection transport and chemical process, and it was caused by vertical mixing and the advection transport process in the lower boundary layer. The contribution of the chemical process in the lower boundary layer was complicated, and its positive contribution played a role in maintaining a high O3 concentration, whereas its negative contribution combined with advection transport resulted in the final dissipation of O3 pollution.

Prediction of the severity of acute pancreatitis using machine learning models.

BACKGROUND: Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in predicting AP severity was not satisfactory. The purpose of this study was to develop predictive models for the severity of AP using machine learning (ML) algorithms and explore the important predictors that affected the prediction results. METHODS: The data of 441 patients in the Department of Gastroenterology in our hospital were analyzed retrospectively. The demographic data, blood routine and blood biochemical indexes, and the CTSI score were collected to develop five different ML predictive models to predict the severity of AP. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC). The important predictors were determined by ranking the feature importance of the predictive factors. RESULTS: Compared to other ML models, the extreme gradient boosting model (XGBoost) showed better performance in predicting severe AP, with an AUC of 0.906, an accuracy of 0.902, a sensitivity of 0.700, a specificity of 0.961, and a F1 score of 0.764. Further analysis showed that the CTSI score, ALB, LDH, and NEUT were the important predictors of the severity of AP. CONCLUSION: The results showed that the XGBoost algorithm can accurately predict the severity of AP, which can provide an assistance for the clinicians to identify severe AP at an early stage.

Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL.

Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in the human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.

Predictive factors for successful sperm retrieval by microdissection testicular sperm extraction in men with nonobstructive azoospermia and a history of cryptorchidism.

This study aims to explore the factors influencing the success rate of the microdissection testicular sperm extraction (Micro-TESE) in patients with nonobstructive azoospermia (NOA) and cryptorchidism. Clinical data of 162 patients with cryptorchidism who underwent Micro-TESE due to infertility from December 2015 to May 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively. In the univariate analysis, significant differences in the age of patient at the time of orchidopexy (median [interquartile range, IQR]: 7.0 [4.0-11.0] years vs 11.5 [9.0-14.5] years, P < 0.001), interval between orchidopexy and Micro-TESE (mean ± standard deviation: 17.5 ± 5.0 years vs 14.4 ± 4.4 years, P < 0.001), severity of cryptorchidism (unilateral [62.8%] vs bilateral [31.6%], P < 0.001; location of cryptorchidism, intra-abdominal [27.3%] vs inguinal [44.8%] vs suprascrotal [66.7%], P < 0.001), volume of the dominant testis (median [IQR]: 17.00 [15.00-19.00] ml vs 14.50 [11.75-16.25] ml, P < 0.001), and levels of follicle-stimulating hormone (FSH; P = 0.004) and testosterone (P = 0.006) were observed between the successful and failed sperm extraction groups. After conducting the multivariate analysis, four of these factors, including unilateral/bilateral cryptorchidism (P < 0.001), location of cryptorchidism (P = 0.032), age of orchidopexy (P < 0.001), and dominant testicular volume, were adopted in the clinical prediction model to evaluate preoperatively the success rate of Micro-TESE for patients with NOA and cryptorchidism. The likelihood of successful sperm retrieval by Micro-TESE in men with NOA and cryptorchidism increased in patients with mild forms of cryptorchidism.

[Exploring Characteristics and Causes of Summer Ozone Pollution Based on Process Analysis in Wuhai].

In recent years, summer O3 pollution has become more severe in Wuhai, where the terrain is complex and industrial parks are densely distributed. However, the characteristics and formation mechanisms of this pollution have not yet been investigated and remain unclear. Analyzing the variation and formation mechanisms of O3 is crucial to the prevention and control of air pollution in this region. By analyzing characteristics and using a WRF-CMAQ model to simulate three O3 pollution periods in Wuhai from June to August 2018, this study explored the causes of O3 pollution based on in-depth process analysis, and the effects of regional transportation and local photochemical reaction on O3 were also discussed. The diurnal variation of ozone exhibited a single-peak distribution, and near-surface O3 was positively correlated with short-wave radiation and temperature, and negatively correlated with relative humidity. The areas of Shizuishan in Ningxia and the Ulanbuhe desert exhibited high O3 values during the day, while the three industrial parks in Wuhai exhibited low values during both the day and night. Process analysis showed that transportation, chemical processes, and their relative magnitudes had a significant impact on O3. Local photochemical reactions and transport during the pollution period in June and July led to an obvious increase in O3, while the impact of chemical processes was about twice as large as that of transport. The increase of O3 in August was mainly caused by transport. Further decomposition of the transportation effect showed that transportation in the south and northwest directions had a remarkable effects on the increase of O3. Together with the emission of O3 precursors, the main sources of transportation were the Yinchuan, Shizuishan, and Bayannaoer regions. Therefore, Wuhai and neighboring cities should strengthen regional joint prevention and control by jointly formulating and implementing control measures for air pollution to reduce the impact of regional transmission on O3.

[Identify the Nitrate Sources in Different Land Use Areas Based on Multiple Isotopes].

Different land uses have different impacts on the water quality of the region. Multiple isotopes (δD-H2O, δ18O-H2O, δ15N-NO3-, and δ18O-NO3-) and the SIAR (stable isotope analysis in R) model were applied to identify the nitrate sources and estimate the proportional contributions of multiple nitrate sources in a river in a typical urban area (the Grand Canal, Hangzhou) and a river in a typical forest and agricultural area (Yuying Riveri). The results indicated that there were different degrees of nitrogen pollution in the Grand Canal and Yuying River; NO3--N and NH4+-N are the predominant forms of nitrogen in the Grand Canal, and the primary form of nitrogen in Yuying River was NO3--N. There was an obvious linear relationship between the hydrogen and oxygen isotopes (R2=0.78). The δD-H2O and δ18O-H2O values for the Grand Canal and Yuying River were distributed along the local meteoric waterline, indicating that precipitation served as the primary water source in these rivers. All of the δ18O-NO3- values of the Grand Canal and Yuying River were lower than 15 ‰. It was revealed that nitrification, rather than denitrification, was the primary N cycling process in the two rivers. The δ15N-NO3-/δ18O-NO3- ratios of some of the samples from the Grand Canal ranged from 1.3 to 2.1, accompanied by low concentrations of DO and NO2-, indicating that denitrification existed in some sections of the Grand Canal. The δ15N-NO3- values of the samples from the Grand Canal (average:6.1‰) were higher than those from the Yuying River (average:2.3‰). The NO3- source contributions differed significantly between the Grand Canal and Yuying River. The contributions of NO3- sources in the Grand Canal were sewage/manure (37.0%) > soil nitrogen (35.7%) > chemical fertilizer (19.1%) > precipitation (8.2%), and those in the Yuying River were chemical fertilizer (46.1%) > soil nitrogen (22.8%) > precipitation (17.3%) > sewage/manure (13.8%). The contribution of the sewage/manure was substantially increased in the Grand Canal in the urban area with stronger human activities primarily due to the sporadic discharge of domestic sewage and urban runoff. Chemical fertilizer is the main NO3- source in the Yuying River near the forest and agricultural area, suggesting that the nitrogen pollution caused by agricultural non-point sources was extremely serious. The contribution of precipitation decreased in the areas of substantial human activities. The isotopic fractionation produced by denitrification was affected by the contributions of the NO3- sources, which were calculated by SIAR model. Sewage/manure and chemical fertilizer produced significant impacts, followed by soil nitrogen and precipitation.

[Nonlinear Response Characteristics and Control Scheme for Ozone and Its Precursors Based on Orthogonal Experimental Methods].

There is a highly nonlinear relationship between ozone concentrations and its precursor emissions in different regions and at different times, which makes developing effective prevention and control measures difficult. An orthogonal experimental method was introduced to assess the influence of ozone precursors and their interactions on ozone formation, clarify the sensitivity of ozone generation, and propose an optimal control scheme. Based on the WRF-Chem air quality model and an emission inventory of air pollutants in Wuhai City in 2018, this study used an ozone pollution event in the Haibowan urban area (August 17 to 20 2018) to investigate the nonlinear response of ozone formation to its precursors. The orthogonal experiment shows that NOx, VOCs interactions with CO, CO, and interactions between pollutants and meteorological factors are the main factors affects ozone concentrations in the Haibowan urban area. Ozone generation was most sensitive to NOx concentrations during the hours 12:00-18:00 when standard values were exceeded. The ozone concentrations decreased significantly by 12.6 µg·m-3 (7.8%) as NOx, VOCs, and CO were reduced by 60%, 30%, and 30%, respectively. Through the analysis of chemical reaction mechanisms, it is concluded that VOCs and CO affect the photochemical reaction by reacting with·OH, HO2·and other free radicals, which causes the significant interaction between VOCs and CO in the generation of ozone. This method provides a new approach for researching the nonlinear response of ozone formation to its precursors and for proposing ozone pollution control schemes.

[Establishment of a High-resolution Anthropogenic Emission Inventory and Its Evaluation Using the WRF-Chem Model for Lanzhou].

City-scale high-resolution anthropogenic emission inventories are an important tool for ambient air quality forecasting and early warning, the analysis of underlying causes, and policy making. At present, city-scale anthropogenic emissions inventories for use in air quality models are scarce for West China. By studying the literature on emission inventories, this paper establishes a city-scale anthropogenic emission inventory for Lanzhou (HEI-LZ16) as the basis for an air quality model. The weather research and forecasting with chemistry (WRF-Chem) model was used to evaluate the applicability of the emission inventory at different resolutions in Lanzhou. The results showed that the emission amounts of SO2, NOx, CO, NH3, VOCs, PM10, PM2.5, BC, and OC in Lanzhou were 25642, 53998, 319003, 10475, 35289, 49250, 19822, 2476, and 1482 t·a-1 in 2016,respectively. Compared with the simulation scenario of multi-resolution emission inventory for China (MEIC), normalized mean error (NME) of O3 and PM2.5 under the HEI-LZ16 scenario decreased by 140.2% and 28.8%, respectively. The HEI-LZ16 inventory is more suitable for application in air pollution research in Lanzhou, which was verified by the WRF-Chem model and the observational data. The spatiotemporal distributions of PM2.5 and O3 were also analyzed using the HEI-LZ16 scenario. The ozone concentration of the maximum daily 8-h average (MDA8) in Lanzhou was low in urban areas and high in the suburbs during winter and spring, and high in the west of the urban valley and its downwind areas during summer and autumn. MDA8 in summer and autumn was influenced by easterly winds and photochemical reactions. In winter, ozone concentrations in urban areas are suppressed by NOx emissions but the concentration decreases. High PM2.5 concentrations are mainly concentrated within the Yellow River Valley. This study shows that there is a pollutant transmission channel along the western side of the Baiyin-Lanzhou Yellow River Valley, which has a greater impact on the ambient air quality in Lanzhou.

Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGß1-MAPK/ERK axis.

Accumulating evidences have suggested that exosomes are closely associated with tumor progression by affecting cell-cell communication. Here, we aimed to investigate the roles and regulatory mechanism of exosomes released from chronic lymphocytic leukemia (CLL). The expression levels of genes and proteins in cells and exosomes were examined by quantitative real-time PCR and Western blotting, respectively. MEC-1 cell-derived exosomes were obtained and co-cultured with human umbilical vein endothelial cells (HUVECs), then the capabilities of cell proliferation, metastasis and angiogenesis of HUVECs were measured by CCK-8, wound healing, transwell and tube formation assay, respectively. Chloride intracellular channel 1 (CLIC1) was significantly increased in CLL patients and markedly enriched in exosomes secreted by CLL cells. Exosomal CLIC1 secreted from MEC-1 cells were successfully transferred into HUVECs and significantly promoted the phenotypes of proliferation, metastasis and angiogenesis of HUVECs. Mechanically, exosomal CLIC1 secreted from MEC-1 cells obviously activated MAPK/ERK signaling through upregulating integrin ß1 (ITGß1) expression in HUVECs. Furthermore, rescue experiments revealed that either silencing ITGß1 or PD98059 treatment obviously reversed the regulatory effects of exosomal CLIC1 secreted from MEC-1 cells in HUVECs. In conclusion, CLL cell-derived exosomes accelerated HUVECs metastasis and angiogenesis through transferring CLIC1 to regulate ITGß1-MAPK/ERK signaling, indicating that CLIC1 may be a therapeutic target of CLL exosomes in the tumor microenvironment.

Full-scale experimental study of methane emission in a loess-gravel capillary barrier cover under different seasons.

The methane emission in a loess-gravel capillary barrier cover (CBC) in winter and summer was investigated by constructing a full-scale testing facility (20 m × 30 m) with a slope angle of 14.5° at a landfill in Xi'an, China. Weather conditions, methane emission, gas concentration, temperature, and volumetric water content (VWC) in the CBC were measured. The temperature and moisture in the CBC showed a typical seasonal pattern of warm and dry in summer and cold and wet in winter. Accordingly, the maximum methane oxidation rate and methane emission were higher in summer. The mean methane influx and methane emission decreased significantly as the VWC increased beyond 40% (i.e., a degree of saturation 0.85) at a depth of 0.85 m, which was near the loess/gravel interface. At this depth, more water was presented in the loess layer in the downslope direction due to capillary barrier effects, which increased the upslope methane emission. More dominant methane emission in the middle- and upper-section of the CBC occurred in summer than in winter as there was less soil moisture to facilitate methane transfer. The LFG balance showed that a significant fraction of the loaded LFG was not accounted in the flux chamber measurements due to the preferential flow along the edges of the CBC. The maximum methane oxidation rate was 93.3 g CH4 m-2 d-1, indicating the loess-gravel CBC could mitigate methane emissions after landfill closure.

Performance of a compacted loess/gravel cover as a capillary barrier and landfill gas emissions controller in Northwest China.

Loess is widely distributed in Northwest China where the rainy season coincides with the warm and vegetation growth period. The use of loess as a capillary barrier cover (CBC) material is promising. However, how the loess/gravel CBC perform as a capillary barrier and landfill gas emissions controller remains elusive. In this study, the performance of a designed CBC comprised 1.3 m-thick compacted loess underlain by 0.3 m-thick gravel in extremely wet and dry years of Xi'an city from 1950 to 2000 was analyzed using numerical modeling. An instrumented CBC test section comprised 0.9 m-thick compacted loess underlain by 0.3 m-thick gravel was constructed to show the hydraulic responses in real conditions from January 2015 to January 2017. The numerical results indicated that the designed CBC performed well as a capillary barrier as no percolation occurred during the extremely wet periods. Despite adopting a CBC of 0.4 m thinner than the designed one, the test section produced only 16.16 mm percolation during the two-year monitoring period, and that can meet the recommended limit of 30 mm/yr. The effect of the capillary break on increasing the water storage within the CBC was observed at the test section in fall. The increased water storage can significantly decrease the gas permeability, and thus improve the performance of the CBC as a LFG emissions controller. Furthermore, the LFG emissions can be controlled to meet the limit set by the Australian guideline by decreasing the bottom gas pressure and artificial watering. Finally, a procedure was proposed to enhance the performance of CBCs.

[Clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma: A report of 10 cases and literature review].

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma (PMAC). METHODS: We retrospectively analyzed the clinical data on 10 cases of PMAC treated in the First Affiliated Hospital of Nanjing Medical University from January 2014 to June 2018. The patients were aged 51－79 (65 ± 14) years, with a medium PSA level of 89 (14.63－128.05) µg/L and Gleason scores of 3 + 3 in 1 case, 3 + 4 in 2, 4 + 3 in 1 and 8 in 6 cases preoperatively, 1 treated by robot-assisted radical prostatectomy and the other 9 by laparoscopic radical prostatectomy. We conducted pelvic cavity lymph node dissection for all the patients and analyzed their prognosis and survival. RESULTS: Operations were successfully completed in all the cases. Pathological examination revealed 2 cases of mucinous adenocarcinoma with signet ring cell carcinoma in the 10 PMAC patients, 2 at stage ≤T2b, 5 at stage ≥T2c, 3 positive at pelvic lymph node dissection and 5 positive at the incision margin. The patients were followed up for 6－48 (median 26) months. Four of the patients were found with biochemical recurrence within 2 years after operation and treated by androgen-deprivation therapy, radiotherapy and chemotherapy, which reduced the PSA level to <1.0 µg/ml in all the 4 cases. CONCLUSIONS: PMAC has a good prognosis. Radical surgery is recommended for moderate and low-risk PMAC and the patients with postoperative biochemical recurrence can benefit from comprehensive treatment of total androgen blockade.

[Identification of biomarkers to response of Tripterygium Glycosides Tablets acting on rheumatoid arthritis by integrating transcriptional data mining and biomolecular network analysis].

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.

Traumatic brachial plexus injury: a study of 510 surgical cases from multicenter services in Guangxi, China.

BACKGROUND: Traumatic brachial plexus injuries are severe lesions, and the incidence of these injuries has been increasing in recent years. METHODS: The clinical data of 510 operated patients with brachial plexus injury recruited from 74 hospitals in Guangxi from 2004 to 2016 were retrospectively studied. RESULTS: Our study included 447 males and 63 females, with an average age of 29.04 years. Traffic accidents were the most common cause of injury (64.71%), especially motorcycle accidents. Closed injuries accounted for 88.24% of cases, and 83.53% of patients had associated injuries, the most common of which were fractures (76.27%). The preoperative predictive value of root injury of MRI and CT was 74.71% and 71.28%, respectively. 44.71% of patients underwent an initial operation within 6 months after the trauma. Regarding the surgery, neurolysis alone, brachial plexus reconstruction, and free functioning gracilis graft accounted for 16.67%, 75.50%, and 4.51%, respectively. A total of 415 patients were followed up with an average time of 47.95 (25-68) months, and anxiety or depression were found among 81.20% of them. Two hundred seventy-six patients suffered from nerve pain, with mild pain present in 67.03% of patients. Additionally, 347 patients were followed up for more than 3 years, 76.81% of patients with C5-C6 injury recovery to useful function, and the procedure of neurolysis alone demonstrated the best efficacy (79.45%). CONCLUSIONS: Brachial plexus injury is still a challenging trauma for surgeons, and traffic accidents are the dominant cause. Timely and effective surgery is important for functional limb recovery.

Down regulation of G protein-coupled receptor 137 expression inhibits proliferation and promotes apoptosis in leukemia cells.

BACKGROUND: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. MATERIALS AND METHODS: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. RESULTS: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. CONCLUSIONS: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia.

Knockdown of immature colon carcinoma transcript 1 induces suppression of proliferation, S-phase arrest and apoptosis in leukemia cells.

Immature colon carcinoma transcript 1 (ICT1), a human mitochondrial translation release factor, is a ribosome-dependent codon-independent peptidyl-tRNA hydrolase. ICT1-deficiency has been recognized as a cell growth inhibitor of hepatoblastoma and glioblastoma multiforme. To explore the role of ICT1 in human leukemia, 2 short hairpin RNAs (shRNAs) targeting ICT1 sequences were designed in leukemia U937 cells. The successful infection of ICT1 in the U937 cells was observed under a fluorescence microscope and further quantified by western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tetrazolium dye (MTT) assay revealed a significant decrease in proliferation of ICT1-knockdown U937 cells on the fourth and fifth day as compared with the control. Depletion of ICT1 resulted in an increase in S phase and sub-G1 (representing cell apoptosis) fractions. Annexin V-APC/7-AAD staining assay confirmed that knockdown of ICT1 played a crucial role in boosting early and late apoptotic programs in U937 cells. Downregulation of ICT1 also altered cyclin A2 transcription expression, caspase-3 activity and p21 protein expression. Additionally, decreased levels of heat shock protein 27 (HSP27) phosphorylation at Ser78 was correlated with knockdown of ICT1 in U937 cells. Thus, we concluded that the regulatory role of ICT1 in leukemia may be used as a potential therapeutic target for the treatment of leukemia.

Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells.

Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.