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Dry eye disease (DED) is a common disorder of tear secretion on the ocular surface caused by multiple factors with dry eyes as the main symptom, but until now studies focusing on relationship between local meteorological factors and ocular surface diseases in Urumqi are very limited. Besides, the effects of long-term and extreme meteorological factors on DED and the lag effect have not been fully evaluated. Electronic case information of 9970 DED outpatients from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) between January 1, 2013, and December 31, 2020, was screened and analyzed. We used a time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) to fit the effects of exposure to different meteorological factors and extreme weather on DED outpatient visits. Subgroup analyses were further performed for gender, age, and season. The results showed that exposure to extremely low mean temperature (P1:RR = 1.18), atmospheric pressure (P1:RR = 1.11), and extremely high relative humidity (P99:RR = 1.35) were the risk factors, while extremely high atmospheric pressure (P90:RR = 0.883) and extremely low humidity (P10:RR = 0.856) appeared to have a positive effect on reduced risk of DED. Relative humidity exhibited a 1-day lag effect (RR = 1.06). Increased mean temperature positively affected female DED patients (RR = 0.761) with similar effects in the cold season (RR = 0.926). However, elevated relative humidity had a negative effect on female patients (RR = 1.14). We conducted the first large sample size time-series analysis study in this major city at the farthest distance from the ocean in the world and in northwest China, confirming the association of DED outpatient visits with the remaining three meteorological factors except wind speed in Urumqi, and a larger sample size multi-center epidemiological study with a longer duration is still needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Some heavy metals are associated with periodontitis; whereas most of these associations have focused on individual metal, there are no specific studies on the effects of combined heavy metal exposure on periodontitis. We conducted an analysis on the association between urinary heavy metal exposure and periodontitis in participants aged 30 years and older using multiple logistic regression and Bayesian kernel machine regression (BKMR). This analysis was performed on data from the National Health and Nutrition Examination Survey from 2011 to 2014. The study found that using logistic regression, the 4th quartile of urinary lead and molybdenum and the 3rd quartile of urinary strontium were positively associated with periodontitis compared to the reference quartile after adjusting for covariates. Odds ratio (OR) with 95% confidence interval (CI) was 1.738 (1.069-2.826), 1.515 (1.025-2.239), and 1.498 (1.010-2.222), respectively. The 3rd and 4th quartiles of urinary cobalt were negatively associated with periodontitis, and their ORs and 95% CIs were 0.639 (0.438-0.934) and 0.571 (0.377-0.964), respectively. The BKMR model showed that urinary barium, lead, and molybdenum were positively associated with periodontitis in a range of concentrations and urinary cobalt, manganese, tin, and strontium were negatively correlated with periodontitis. Furthermore, the overall association between urinary heavy metals and periodontitis was positive. Our study provides evidence for an association between exposure to multiple urinary heavy metals and periodontitis. However, further longitudinal studies are needed to explore the specific mechanisms involved., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies addressing the impact of environmental factors on TB prognosis are scarce, with only some studies examining the effect of particulate pollutants on TB mortality. Moreover, few studies have evaluated the effects of multiple gaseous pollutants and greenness exposures on newly treated TB patients on a large population scale., Methods: Through the Centers for Disease Control and Prevention, data were collected from January 1, 2015 to December 31, 2020 for newly treated TB patients in Anhui Province, China. Data on gaseous pollutants sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were collected through the National Earth System Science Data Center of China. Normalized vegetation index data were obtained through NASA. The Cox proportional risk model was also applied to calculate the hazard ratios of SO 2 , NO 2 , CO, O 3 , and NDVI with 95% confidence intervals for mortality among newly treated TB patients., Results: Multifactorial Cox regression analysis showed that for every 0.10 μg/m 3 increase in SO 2 , the risk of death among newly treated TB patients increased by 13.2% (HR = 1.132, 95% CI: 1.045-1.1.225), for every 10 μg/m 3 increase in NO 2 , the risk of death among newly treated TB patients increased by 11.4%, and for each 0.1 mg/m 3 increase in CO, the risk of death among newly treated TB patients increased by 5.8%. For each 0.1 increase in NDVI 250m-buffer and 500m-buffer, the risk of death among newly treated TB patients decreased by 8.5% and 6.4%, respectively. The effect of gaseous pollutants on mortality decreased progressively with elevated greenness exposure when greenness exposure was grouped from low to high., Conclusion: Gaseous pollutants are a risk factor during the treatment of newly treated TB patients and greenness exposure is a protective factor. Higher greenness exposure reduces the risk of death due to exposure to gaseous pollutants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thiopental sodium (TPTS) is a barbiturate general anesthetic, while its effects on hypoxia/reoxygenation (H/R)-induced injury are still unclear. This study aimed to investigate whether TPTS exerts protective effects against the H/R-induced osteoblast cell injury and explore the underlying mechanisms. Osteoblast cell injury model was induced by the H/R condition, which was treated with or without TPTS. Cell viability and lactate dehydrogenase (LDH) release were determined by the corresponding commercial kits. The levels of oxidative stress were determined in the experimental groups. Cell apoptosis and Caspase-3 activities were determined by propidium iodide staining and substrate-based assay, respectively. Western blotting and qRT-PCR were performed to measure the mRNA and protein levels, respectively. Treatment with TPTS was able to increase cell viability and reduce LDH release in H/R-induced osteoblasts. Additionally, TPTS regulated oxidative stress in H/R-induced osteoblasts by suppressing malondialdehyde (MDA) and reactive oxygen species (ROS) as well as boosting superoxide dismutase (SOD). TPTS was able to suppress cell apoptosis by suppressing Caspase-3 activity and cleavage. TPTS exerted protective effects against cell injury and apoptosis induced by the H/R conditions, which were associated with its regulation of Akt signaling. Moreover, TPTS induced osteoblast differentiation under the H/R condition. In summary, TPTS attenuates H/R-induced injury in osteoblasts by regulating AKT signaling., (© 2023. The Society for In Vitro Biology.)

Conjunctivitis is an inflammatory disease of the conjunctival tissue caused by a variety of causes; despite the conjunctiva being directly exposed to the external atmospheric environment, the important role of air pollution is not fully evaluated, especially in areas with poor air quality undergoing rapid economic and industrial development. Information on 59,731 outpatient conjunctivitis visits from 1 January 2013 to 31 December 2020 was obtained from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China), and data on six air pollutants including particulate matter with a median aerometric diameter of less than 10 and 2.5 mm (PM 10 and PM 2.5 , respectively), carbon monoxide (CO), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) from eleven standard urban background fixed air quality monitors were also recorded. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effect of exposure to air pollutants on the risk of conjunctivitis outpatient visits. Further subgroup analyses were conducted for gender, age, and season, as well as the type of conjunctivitis. Single and multi-pollutant models showed that exposure to PM 2.5 , PM 10 , NO 2 , CO, and O 3 was associated with increased risk of outpatient conjunctivitis visits on the lag 0 day and various other lag days. Variations in the effect estimates on direction and magnitude were found in different subgroup analyses. We conducted the first time-series analysis with the longest duration as well as the largest sample size in Northwest China, which provides evidence that outpatient conjunctivitis visits is significantly associated with air pollution in Urumqi, China. Meanwhile, our results demonstrate the effectiveness of SO 2 reduction in reducing the risk of outpatient conjunctivitis visits in the Urumqi region and reaffirm the need to implement special air pollution control measures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Conjunctivitis is a common multifactorial inflammatory ocular surface disease characterized by symptoms such as congestion, edema, and increased secretion of conjunctival tissue, and the potential effects of meteorological factors as well as extreme meteorological factors on conjunctivitis and their lagging effects have not been fully evaluated. We obtained the electronic case information of 59,731 outpatients with conjunctivitis from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) for the period from January 1, 2013, to December 31, 2020. Meteorological data for daily mean temperature (°C), daily relative humidity (%), daily average wind speed (m/s), and atmospheric pressure (hPa) were obtained from the China Meteorological Data Sharing Service. The air pollutant data were obtained from 11 standard urban background fixed air quality monitors. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effects of exposure to different meteorological factors and extreme weather on conjunctivitis outpatient visits. Subgroup analyses were performed on gender, age and season, and type of conjunctivitis. Univariate and multifactorial model results indicated that each 10-unit increase in mean temperature and relative humidity was associated with an increased risk of conjunctivitis outpatient visits, while each 10-unit increase in atmospheric pressure was associated with a decreased risk. The results of the extreme weather analysis suggested that extremely low levels of atmospheric pressure and relative humidity as well as extreme levels of temperature were associated with an increased risk of outpatient conjunctivitis visits, and extreme wind speeds were associated with a decreased risk. The results of the subgroup analysis suggested gender, age, and seasonal differences. We conducted the first large sample size time-series analysis in the large city furthest from the ocean in the world and confirmed for the first time that elevated mean temperature and extreme low levels of relative humidity in Urumqi were risk factors for local conjunctivitis outpatient visits, while elevated atmospheric pressure and extreme low levels of wind speed were protective factors, and there were lagged effects of temperature and atmospheric pressure. Multicenter studies with larger sample sizes are needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Some previous studies had linked air pollutants and greenness to the risk of death from tuberculosis (TB). Only a few studies had examined the effect of particulate matter (PM 2.5 ) on the mortality of TB, and few studies had assessed the impact and interaction of multiple air pollutants and greenness on the mortality of newly treated TB patients. The study included 29,519 newly treated TB patients from three cities in Anhui province. We collected meteorological data and five pollutants data from The National Meteorological Science Center and air quality monitoring stations. Greenness data were generated by remote sensing inversion of medium-resolution satellite images. We geocoded each patient based on the residential address to calculate the average exposure to air pollutants and the average greenness exposure for each patient during treatment. The Cox proportional risk regression model was used to evaluate the effects of air pollutants and greenness on mortality in newly treated tuberculosis patients. Our results found that the higher the concentration of air pollutants in the living environment of newly treated TB patients, the greater the risk of death: HR 1.135 (95% CI: 1.123-1.147) and HR 1.333 (95% CI: 1.296-1.370) per 10 μg/m 3 of PM 2.5 and SO 2 , respectively. Greenness reduced the mortality among newly treated TB patients: HR for NDVI exposure 0.936 (95% CI: 0.925-0.947), HR for NDVI_250m exposure 0.927 (95% CI: 0.916-0.938), and HR for NDVI_500m exposure 0.919 (95% CI: 0.908-0.931). Stratifying the cohort by median greenness exposure, HRs for air pollutants were lower in the high greenness exposure group. Mortality in newly treated TB patients is influenced by air pollutants and greenness. Higher green exposure can mitigate the effects of air pollution. Improving air quality may help reduce mortality among newly treated TB patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Traffic noise has attracted much attention as a significant and intractable public health threat. This study was designed as a systematical review to explore the association of traffic noise with different indicators of obesity, thus providing updated quantitative estimates for the pooled effect estimates of the existing literature. We conducted an extensive search for epidemiological studies that investigated the association of traffic noise with obesity in three electronic databases till February 23, 2021. We used random-effects meta-analysis to calculate the summary effect estimates for each 10-dB(A) increase in noise and compared the highest with the lowest category of noise in relation to seven obesity indicators. Meanwhile, we assessed the risk of bias and the overall quality of the evidence of each study as well as the level of evidence for each exposure-outcome pair. The initial search identified 30 studies, 13 of which were ultimately included. The meta-analysis for the highest versus the lowest category of noise exposure was generally associated with higher waist circumfluence (WC) ranging from 0.326 cm (95% confidence interval (CI) = 0.078, 0.574) to 0.705 cm (95% CI = 0.071, 1.340) and higher odds of central obesity ranging from 1.055 (95% CI = 1.000, 1.109) to 1.167 (95% CI = 1.037, 1.298). When the continuous exposure (each 10 dB(A) increase in noise) was introduced, similar results were found. This study indicated positive associations of traffic noise with WC and central obesity. However, in consideration of some limitations, there is an urgent need for future studies to increase the sample size, discriminate the etiological differences in different noise and obesity indicators, and thoroughly consider socioeconomic status., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A growing number of biological studies suggest that exogenous sulfur dioxide (SO 2 ) at a certain concentration may promote human resistance to Mycobacterium tuberculosis. However, the results of most relevant studies are inconsistent, and few studies have explored the relationship between SO 2 exposure and tuberculosis risk at provincial level. In addition, occupational exposure has long been considered to have a certain impact on the human body, so for the first time, we discussed the differences between different occupations in the study on the relationship between air pollutant exposure and tuberculosis risk, and evaluated the impact of occupational exposure. This study aimed to explore the association between short-term SO 2 exposure and the risk of outpatient visits to tuberculosis in Anhui province and 16 prefecture-level cities from 2015 to 2020. We used several models for multi-stage analysis, including distributed lag nonlinear model (DLNM), Poisson generalized linear regression model, and random-effects model. The association was assessed using the 28-day cumulative lag effect RR and 95%CI for each 10-unit increase in SO 2 concentration. We divided all patients into the following six occupations: Worker, Farmer, Retired people, Children and Students, Cadre and Office clerk, and Service staff (catering, business, etc.). Sex, age, and season were analyzed by subgroup. Finally, the robustness of the multi-pollutant model was tested. At provincial level, the overall effect value of SO 2 was RR=0.8191 (95%CI: 07702~0.8712); after grouping all patients by occupation, the association found only among Farmers (RR = 0.7150, 95%CI: 0.6699-0.7632, lag 0-28 days) and Workers (RR = 0.8566, 95%CI: 0.7930-0.9930, lag 0-4 days) was still statistically significant. Estimates for individual cities and using random-effects models to estimate average associations showed that SO 2 exposure was associated with a reduced risk of outpatient TB visits in 14 municipalities, which remained significant when aggregated (RR = 0.9030, 95%CI: 0.8730-0.9340). Analysis of patients grouped by occupation in each municipality showed that statistical significance was again observed only in the Farmer (RR = 0.8880, 95%CI: 0.8610-0.9160) and Worker (RR = 0.8250, 95%CI: 0.7290-0.9340) groups. Stratified analysis of age, sex, and season showed that the effect of SO 2 exposure was greater for middle-aged people (18-64 years old) and males, and less for seasonal changes. In summary, we found that exposure to SO 2 reduces the risk of outpatient visits to tuberculosis, with farmers and workers more susceptible to SO 2 . Gender and age had a greater impact on the risk of TB outpatient visits than seasonal variations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There is growing evidence that air pollution plays a role in TB, and most studies have been conducted in the core countries with inconsistent results. Few studies have comprehensively included the six common air pollutants, so they cannot consider whether various pollutants interact with each other. Our objectives were to investigate the association between short-term exposure to six common air pollutants and the risk of tuberculosis outpatient visits in Fuyang, China, 2015-2020. We combined the two models to explore the effects of exposure to six air pollutants on the risk of tuberculosis outpatient visits, including the Poisson generalized linear regression model and distributed lag non-linear model (DLNM). We performed stratified analyses for the season, type of cases, gender, and age. We used the lag-specific relative risks and cumulative relative risk obtained by increasing pollutant concentration by per 10 units to evaluate the connection between six air pollutants and TB; PM 2.5 (RR = 1.0018, 95% CI: 1.0004-1.0032, delay of 12 days) and SO 2 (RR = 1.0169, 95% CI: 1.0007-1.0333, lag 0-16 days) were 0.9549 (95% CI: 0.9389-0.9712, lag 0 day) and 0.8212 (95% CI: 0.7351-0.9173, 0-20-day lag). Stratified analyses showed that seasonal differences had a greater impact on TB, males were more likely to develop TB than females, older people were more likely to develop TB than younger people, and air pollution had a great impact on new cases. Exposure to O 3 , CO, PM 10 , PM 2.5 , and NO 2 increases the risk of TB outpatient visits, except SO 2 which reduces the risk. The incidence of TB has seasonal fluctuations. It is necessary for the government to establish a sound environmental monitoring and early warning system to strengthen the monitoring and emission management of pollutants in the atmosphere. Management, prevention, and treatment measures should be developed for high-risk groups (males and older people), reducing the risk of TB by reducing their specific behaviors and changing their lifestyle. We need to pay more attention to the impact of seasonal effects on TB to protect TB patients and avoid a shortage of medical resources, and it is necessary for the government to develop some seasonal preventive measures in the future., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer is a complex and multifactorial disease which stems significantly from both environmental and genetic factors. A growing number of epidemiological studies have suggested that ambient air pollution (AAP) exposure may play an important role in breast cancer development. However, no consistency has been reached concerning whether high levels of air pollutant exposure were related to increased breast cancer risk among the current evidence. To further clarify such association of long-term AAP exposure with risk of breast cancer, a systematic review and meta-analysis of available evidence was performed. An extensive literature search in 3 academic databases was conducted before March 10, 2020. The risk of bias (RoB) for each individual study was evaluated with a domain-based assessment tool, developed by the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Meta-estimates for air pollutant-breast cancer combinations were calculated for a standardized increment in exposure by random-effect models. The confidence level in the body of evidence and the certainty of evidence was also assessed for each air pollutant-breast cancer combination. The initial search identified 5446 studies, and 18 of them were eligible. The pooled analysis found an increased risk of breast cancer was associated with an increase in each 10 μg/m 3 in nitrogen dioxide (NO 2 ) exposure (hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01, 1.04), while particulate matter with aerodynamic diameters ≤ 2.5 μm and 10 μm (PM 2.5 , PM 10 ) revealed no statistically significant associations with breast cancer risk. Our evaluation on the certainty of evidence indicates that there was a "moderate level of evidence" in the body of evidence for an association of NO 2 exposure with an increased breast cancer risk and an "inadequate level of evidence" in the body of evidence for an association of PM 2.5 and PM 10 exposure with an increased breast cancer risk. Our study suggests long-term exposure to NO 2 is related to an increased risk of breast cancer. However, in consideration of the limitations, further studies, especially performed in developing countries, with improvements in exposure assessment, outcome ascertainment, and confounder adjustment, are needed to draw a definite evidence of a causal relationship., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Several factors can affect the risk of recurrence after curative resection of colorectal cancer (CRC). We aimed to develop a risk model for recurrence after definitive treatment of Stage I-III CRC using data from a nationally representative database and to develop an individualized web-based risk calculator., Methods: A random sample of patients who underwent resection for Stage I-III CRC between 2006 and 2007 at Commission on Cancer (CoC) accredited centers were included. Primary data regarding first recurrence was abstracted from medical records and merged with the National Cancer Database. Multivariable cox regression analysis was used to test for factors associated with cancer recurrence, stratified by stage. Model performance was tested by c statistic and calibration plots. Hazard Ratios were utilized to develop an individualized web-based recurrence prediction tool., Results: A total of 8249 patients from 1175 CoC centers were included. Of these, 1656 (20.1%) patients had a recurrence during 5 years of follow-up. Median time to recurrence was 16 months. The final predictive models displayed excellent discrimination and calibration with concordance indexes of 0.7. The online calculator included 12 variables, including tumor site, stage, time since surgery, and surveillance intensity. Output is displayed numerically and graphically with an icon array., Conclusions: Using primarily abstracted recurrence data from a random sample of patients treated for CRC at CoC accredited centers across the United States, we successfully created an individualized CRC recurrence risk assessment tool. This web-based calculator can be used by physicians and patients in shared decision making to guide management discussions., Trial Registration: ClinicalTrials.gov Registration Number: NCT02217865.

Objective: This study aimed to determine the risk of severe postoperative complications (SPCs) in patients with gastric cancer and to construct a nomogram based on independently related factors to identify high-risk patients., Methods: We conducted a prospective study of 636 consecutive patients with gastric cancer who underwent radical gastrectomy. Degrees of sarcopenia and obesity were calculated before surgery. Factors contributing to SPCs were determined using univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of SPCs., Results: Logistic analysis revealed that sarcopenic obesity, age, open surgery, and combined resection were independent prognostic factors for SPCs. Sarcopenic obese patients have the highest risk in all patients (sarcopenic obesity vs normal, OR = 6.575 p = 0.001; sarcopenic obesity vs obesity, OR = 5.833 p = 0.001; sarcopenic obesity vs sarcopenia, OR = 2.571 p = 0.032), while obese patients share the similar rate of SPCs with normal people (obesity vs normal, OR = 1.056 p = 0.723). The nomogram we constructed was able to quantify the risk of SPCs reliably (c-index, 0.737)., Conclusions: Sarcopenic obesity, together with age, open surgery, and combined resection are independent predictors of SPCs. Obesity will significantly increase the risk of SPCs in sarcopenic patient with gastric cancer, but it will not bring higher risk to normal patients. Our nomogram is a simple and practical instrument to identify patients at high risk of surgical complications.

Background: As a tricyclic glycopeptide antibiotic used to treat acute infections, Vancomycin (VAN) is often administered with piperacillin/tazobactam (PT) to treat various infections in clinical practice. However, whether the combination of these two drugs, compared to VAN alone, can cause an increased risk of acute kidney injury (AKI) remains controversial., Objectives: This study aims to identify the correlation between the development of AKI and the combined use of VAN and PT., Methods: We conducted a meta-analysis of eight observational cohort studies (a total of 10727 participants received VAN and PT versus VAN and other β-lactams). PubMed, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, Wan Fang Digital Periodicals Database (WFDP), and China Science Citation Database (CSCD) were searched through April 2017 using "vancomycin" and "piperacillin" and "tazobactam" as well as "acute kidney injury" or "acute renal failure" or "AKI" or "ARF" or "nephrotoxicity." Two reviewers extracted the data and assessed the risk of bias., Results: A correlation was found between the development of AKI and concurrent use of VAN and PT compared with concomitant VAN and β-lactams (OR 1.57; 95% CI, 1.13-2.01; I 2  = 76.4%, p < 0.001). Similar findings were obtained in an analysis of studies comparing concurrent VAN and PT use with concurrent VAN and β-lactam (cefepime) use (OR 1.50; 95% CI, 1.07-1.93; I 2  = 80.5%, p < 0.001). Exclusion of fair-quality and low-quality articles did not change the results (OR 1.49; 95% CI, 1.06-1.92; I 2  = 84.1%, p < 0.001)., Conclusions: Regarding β-lactam therapy in clinical practice, an elevated risk of AKI due to the combined use of VAN and PT should be considered.

Background: Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane., Methods: The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015., Results: Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %., Conclusions: Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

Genetic alterations in the PI3K/AKT cascade have been linked to various human cancers including acute myeloid leukemia (AML) and have emerged to be promising targets for treatment. In this study, we explored the molecular mechanism and clinical implication of a specific allosteric AKT inhibitor, MK-2206, in the treatment of AML. Four leukemia cell lines, MV-4-11, MOLM-13, OCI/AML3, and U937, were used. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Expression of anti-apoptotic protein family and glycogen synthase kinase 3β (GSK3β) signaling was determined by western blotting. Drug combination effects of MK-2206 with cytarabine were evaluated by cell proliferation assay, and the combination index values were calculated by CompuSyn software. MK-2206 had no effect on normal peripheral blood mononuclear cells, but induced G1-phase arrest and apoptosis in leukemia cells. Among anti-apoptotic Bcl-2 family members, only myeloid cell leukemia-1 (Mcl-1) was significantly suppressed. Mcl-1 suppression by MK-2206 was closely associated with decreased GSK3β phosphorylation at Ser9, an event leads to GSK3β activation. Furthermore, the effect of MK-2206 on Mcl-1 downregulation was abolished by GSK3β inhibitor, lithium chloride and proteasome inhibitor, MG-132, suggesting that MK-2206 acted through a GSK3β-mediated, proteasome-dependent protein degradation. In addition, co-administration of MK-2206 with cytarabine could enhance the cytotoxic efficacy of cytarabine in leukemia cell lines. In conclusion, we have demonstrated that MK-2206 is an active agent in AML and its efficacy as in combination with cytarabine is implicated.

Background: With advances in multimodality therapy, colorectal cancer survivors are living longer. However, little is known about the quality of their long-term survival. We investigated the functional outcomes and symptoms among long-term survivors., Methods: A cross-sectional study of 1,215 long-term (>5 years) colorectal cancer survivors was conducted using a validated disease-specific questionnaire. Younger onset survivors (18-50 years) were matched 1:2 to later onset survivors (>50 years). Standardized mean scores were compared using one-way ANOVA. Key patient and treatment factors that impact function and symptoms were assessed by multivariate linear regression., Results: Eight hundred thirty survivors responded at an interval of 10.8 ± 3 years from diagnosis (68% response rate). Younger onset survivors underwent more surgery (97.9 vs. 93.6%, P < 0.001) and received more chemotherapy (86.1 vs. 77.7%, P = 0.004). Anxiety, body image, sexual dysfunction, embarrassment by bowel movements, micturition problems, and impotence were significant concerns. Younger onset survivors reported worse anxiety, body image, and embarrassment with bowel movements, whereas later onset survivors highlighted sexual dysfunction, micturition problems, and impotence. Age at diagnosis was a key independent determinant of long-term function and symptoms., Conclusion: Long-term survivors of CRC face ongoing functional deficits and symptoms, and their survivorship experience differs by age. Age at diagnosis should serve as a basis for tailored, personalized survivorship care plans.

The growth arrest-specific 6 (GAS6) gene product participates in platelet activation and granulocyte interaction with the endothelium. Our case-control study aimed to determine whether polymorphism of GAS6 was associated with predisposing risk or specific clinical manifestations of systemic lupus erythematosus (SLE). Two of the single-nucleotide polymorphisms (SNPs) of the GAS6 gene, GAS6 834 + 7G/A (rs8191974) and GAS6 +1332C/T (rs1803628), were investigated in 83 SLE patients and 89 non-lupus control subjects. We demonstrated that among lupus patients, the GAS6 +1332 T allele was more prevalent in patients with cutaneous vasculitis (allele T 41.7 % in patients with cutaneous vasculitis compared with 18.3 % in patients without vasculitis, odds ratio (OR) 3.2, 95 % confidence interval 1.3-8.0, p = 0.016). In conclusion, GAS6 polymorphism is positively associated with cutaneous vasculitis in SLE patients, which suggests that GAS6 polymorphism could be a genetic marker for SLE with cutaneous vasculitis.

Purpose: We evaluated clinical features and survival outcomes among patients with signet ring and mucinous histologies of colorectal adenocarcinoma by using data from the National Cancer Data Base (NCDB)., Methods: Patients aged 18-90 years with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified from the NCDB. Site-stratified (colon vs. rectum) survival analysis was performed by multivariate relative survival adjusted for multiple clinicopathologic and treatment variables., Results: The study included 244,794 patients: 25,546 (10%) with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous, non-signet ring adenocarcinoma. Mucinous and signet ring cancers were more frequently right-sided (60% and 62%, respectively) than were nonmucinous, non-signet ring adenocarcinomas (42%, P < 0.001). Signet ring histology was associated with a higher stage (P < 0.001), and 77.2% of signet ring tumors were high-grade lesions, compared with 20% of mucinous and 17% of non-signet ring, nonmucinous adenocarcinomas (P < 0.001). After adjustment for covariates, signet ring histology was independently associated with higher risk of death [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51, and HR 1.57, CI 1.38-1.77, for tumors located in the colon and rectum, respectively]. Mucinous tumors of the rectum (HR 1.22, CI 1.16-1.29), but not the colon (HR 1.03, CI 1.00-1.06), were associated with increased risk of death., Conclusions: Signet ring cell adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the rectum are associated with poorer survival. These aggressive histologic variants of colorectal adenocarcinoma should be targeted for research initiatives to improve outcomes.

Background: Because of its rarity, adenocarcinoma of the small intestine is frequently compared to adenocarcinoma of the colon, although the validity of this comparison is not known., Methods: Patients with small and large bowel adenocarcinoma (SBA and LBA) diagnosed between 1988 and 2007 were identified from the Surveillance, Epidemiology, and End Results registry. Age-standardized incidence and mortality rates were determined. Cancer-specific survival (CSS) stratified by stage and by number of assessed lymph nodes was calculated., Results: A total of 4518 and 261,521 patients with SBA and LBA, respectively, were identified. In comparison to LBA, patients with SBA were younger and presented with disease of higher stage and histologic grade. The age-standardized incidence rates decreased for LBA (-1.24% per year) but increased for SBA (+1.47% per year). Although age-standardized mortality rates decreased for both LBA and SBA, the decreases were more pronounced for LBA. Five-year CSS was worse for resected SBA compared with resected LBA, although this difference diminished when comparing cases having eight or more lymph nodes assessed. The relative reduction in CSS when selecting eight or more lymph nodes was much greater for duodenal as opposed to jejunal/ileal subsite of the small bowel. With nodal selection the absolute difference in CSS between LBA and SBA for stages I, II, and III was 13, 15.9, and 18.5%, respectively., Conclusions: Adequate nodal assessment is much less common in SBA than LBA; and it appears that SBA, in particular duodenal adenocarcinoma, is understaged. Even after corrections to minimize the effect of stage migration and inadequate lymph node evaluation, SBA demonstrated distinctly worse CSS than LBA.

Randomized trials conducted in the 1980s have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy in treating stage-III colon cancer. However, the initiation of adjuvant chemotherapy is just the first step for survival improvement. Little is known about the actual completion rate of such a therapy in the community. The objectives of this study were to measure the initiation and completion rate of adjuvant chemotherapy and to identify the associated factors. We studied 12,265 patients aged 65+ diagnosed with stage-III colon cancer between 1991 and 2005 who were identified from the Surveillance, Epidemiology, and End Results-Medicare linked database. Chemotherapy initiation was defined as at least one claim indicating the use of chemotherapy. The first and last claims were used to measure the length of chemotherapy. A complete course of chemotherapy was defined as 8-13 months for 1991-1995 cohort and 5-7 months for 1996-2005 cohort according to clinical guideline. Of the 12,265 patients, 64.4% received adjuvant chemotherapy within 3 months after tumor resection. Among those who had chemotherapy initiated, 62.2% (or 38.0% of 12,265 patients) received a complete course of chemotherapy. Patient's age at diagnosis, marital status, and comorbidity score were the significant predictors for chemotherapy initiation. These variables remained significant in predicting chemotherapy completion after adjusting for year of diagnosis and other factors. In conclusion, initiation and completion of chemotherapy was largely influenced by patient's age, marital status and comorbidity. Further investigation is needed to explore the cause of these differences in adherence to standard treatment that is essential for better quality of cancer care.

Background: Although international studies of young gastric cancer patients have mainly reported favorable survival outcomes compared with older patients, US-based experiences have shown a wider spectrum of outcomes. We examined the impact of young age (under 45 years) on the presentation and survival outcomes of gastric adenocarcinoma., Methods: A total of 33,236 patients with gastric adenocarcinoma were identified within the 1988-2006 Surveillance, Epidemiology, and End Results (SEER) registry. Multivariate regression analysis of relative survival was performed to adjust for covariate effects using generalized linear models., Results: Young patients were more likely than older patients to have advanced nodal and distant metastatic disease at presentation (P < 0.001 for both). Unadjusted relative survival analysis demonstrated younger patients to have favorable stage-stratified survival when compared with middle-aged and older patients. These findings persisted after adjusting for covariates. After stratifying for receipt of cancer-directed surgery, younger age was associated with more favorable stage-stratified relative survival., Conclusions: This is the largest US population-based study of age-related gastric cancer outcomes. Although young patients with gastric cancer present with more advanced disease, their adjusted stage-stratified relative survival is more favorable than that of older patients. This study supports a stage-dependent treatment approach in younger populations.

Galectin-3 is a beta-galactoside-binding lectin which is involved in modulating inflammation and apoptosis. Elevated expression of galectin-3 has been demonstrated in synovium of rheumatoid arthritis (RA). The aim of our study is to investigate the genetic polymorphisms of galectin-3 in association with RA. Polymorphisms of galectin-3 gene (LGALS3) were compared between 151 RA patients and 182 healthy subjects in Taiwan. Variants at two LGALS3 single nucleotide polymorphism (SNP) sites (rs4644 and rs4652, corresponding to LAGLS3 +191 and +292) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide probe hybridization, respectively. The allelic carriage of LGALS3 +292C was increased in patients with RA (66.9% in RA vs. 52.7% in controls, odds ratio=1.8, 95% confidence interval=1.2-2.8, p=0.009). These results implicate that the genetic polymorphisms in galectin-3 gene may contribute to development of RA.

Background: Treatment of distal rectal cancer remains clinically challenging and includes proctectomy and coloanal anastomosis (CAA) or abdominoperineal resection (APR). The purpose of this study is to evaluate operative and pathologic factors associated with long-term survival and local recurrence outcomes in patients treated for distal rectal cancer., Methods: A retrospective consecutive cohort study of 304 patients treated for distal rectal cancer with radical resection from 1993 to 2003 was performed. Patients were grouped by procedure (CAA or APR). Demographic, pathologic, recurrence, and survival data were analyzed utilizing chi-square analysis for comparison of proportions. Survival analysis was performed using Kaplan-Meier method and log-rank test for univariate and Cox regression for multivariate comparison., Results: The median tumor distance from the anal verge was 2 cm [interquartile range (IQR) 0.5-4 cm]. Margins were negative in all but four patients (one distal, 0.3%; three radial, 1%). The 5-year overall survival rate was 82% (88.6% stage pI, 80.5% stage pII, 67.9% stage pIII). Older age, advanced pathologic stage, presence of lymphovascular or perineural invasion, earlier treatment period, and APR surgery type were associated with worse survival on multivariate analysis. The 5-year local recurrence rate was 5.3% after CAA and 7.9% after APR (p = 0.33)., Conclusions: Low rates of local recurrence and good overall survival can be achieved after treatment of distal rectal cancer with stage-appropriate chemoradiation and proctectomy with CAA or APR. Sphincter preservation can be achieved even with distal margins less than 2 cm.

Background: Conditional survival estimates provide useful prognostic information for cancer survivors. The objective of this study was to determine conditional survival estimates for melanoma patients with substages of stage III disease., Materials and Methods: A retrospective analysis of 760 patients who underwent lymphadenectomy for node-positive melanoma was conducted, and patients were stratified into substages: IIIA, IIIB, and IIIC. The 5-year conditional disease-free survival (DFS) and disease-specific survival (DSS) were calculated following lymphadenectomy using the methods of Kaplan and Meier and were reassessed for survivors on an annual basis. Multivariate Cox regression models were used to calculate adjusted conditional DFS and DSS accounting for age, gender, tumor histology, and extracapsular extension., Results: For patients with IIIA, IIIB, and IIIC disease, 5-year conditional DSS from treatment to year 5 improved from 78% to 90%, 54% to 79%, and 39% to 78%, respectively. For 5-year conditional DFS over the same period, the estimates increased from 65% to 79%, 37% to 81%, and 26% to 92%, respectively. Male patients experienced decreased 5-year conditional DSS and DFS across all substages, with the most pronounced effect on DSS in stage IIIC. Multivariate analysis demonstrated that survival differences among stage IIIC patients based on histologic subtype and extracapsular extension decreased over time., Conclusions: Conditional survival estimates are more optimistic and realistic for cancer survivors than traditional survival estimates over time. For node-positive melanoma survivors, 5-year conditional DFS and DSS improve significantly over time. These estimates are critical to treatment decisions and non-treatment-related planning for both clinicians and patients.

Our previous in vitro study has shown that toluidine blue (TB)-mediated lethal photosensitization of periodontal pathogens (PPs) from periodontal patients is possible. The purpose of this study was to investigate whether TB-mediated photosensitization exerted damaging effects on periodontal tissues in mice. Twenty-four mice were randomly divided into four groups; the experimental photodynamic therapy (PDT) group was treated with 1 mg/ml TB and light irradiation (60 J/cm(2), 635 nm, 337 s). Those in control groups were subjected to 140 J/cm(2) laser irradiation alone or to 2.5 mg/ml TB alone or received neither TB nor light exposure. All the mice were killed 72 h after they had been subjected to PDT, and periodontal tissue samples were taken for histological examination. During the 72 h observation period, no mice showed any distress. No necrotic or inflammatory changes were found in the gingiva, dentin, dental pulp or alveolar bone of the mice in any of the groups in this study. The results suggest that TB-mediated PDT is a safe antimicrobial approach for the treatment of periodontopathy without damaging effects to adjacent normal tissues.

The effects of landscape characteristics on surface water quality were evaluated in terms of land-use condition, soil type and slope. The case area, the Chichiawan stream in the Wulin catchment in Taiwan, is Formosan landlocked salmon's natural habitat. Due to the agriculture behavior and mankind's activities, the water and environmental quality has gradually worsened. This study applied WinVAST model to predict hydrological responses and non-point source pollution (NPSP) exports in the Wulin catchment. The land-use condition and the slope of land surface in a catchment are major effect factors for watershed responses, including flows and pollutant exports. This work discussed the possible variation of watershed responses induced by the change of land-use condition, soil type and slope, etc. The results show that hydrological responses are highly relative to the value of Curve Number (CN); Pollutant exports have large relation to the average slope of the land surface in the Wulin catchment.

Hepatitis C virus (HCV) infection is frequently associated with anti-SSA/Ro and anti-SSB/La autoantibodies. The objective of this study is to examine the prevalence of anti-SSA/Ro and anti-SSB/La autoantibodies in HCV-infected patients and their possible associations with HLA-DRB1 polymorphism in Chinese patients in Taiwan. About 288 HCV-infected patients were recruited for autoantibody detection and HLA-DRB1 typing. Anti-SSA/Ro and anti-SSB/La autoantibodies were detected in 12.8 and 9.7% of HCV-infected patients. Anti-SSA/Ro antibody was positively associated with age over 55 [p = 0.04; odds ratio = 2.17; 95% confidence interval (CI), 1.03-4.57]. Anti-SSB/La antibody was negatively associated with HLA-DR2 carriage (p = 0.024; odds ratio = 0.30; 95% CI, 0.10-0.90). No significant correlation was found between autoantibody production and gender, autoimmune manifestation, presence of cirrhosis, or hepatocellular carcinoma in HCV infection. In conclusion, anti-SSA/Ro and anti-SSB/La antibodies present frequently in HCV-infected patients. Anti-SSB/La antibody is negatively associated with HLA-DR2 in HCV-infected patients in Taiwan.

Employing a different culture strategy, we obtained a greatly improved frequency of embryo rescue in intersubgeneric soybean hybrids. Successful crosses were obtained in 31 different genotype combinations between nine Brazilian soybean lines as the female parents and 12 accessions from Glycine canescens, G. microphylla, G. tabacina and G. tomentella. The hybrid pod retention rate dropped to about 10% during the first 8 days after pollination and stayed largely unchanged up to the 20th day. Immature harvested seeds fell into three size groups: Group 1, smaller than 1.3 mm (mostly empty seed coats); Group 2, 1.9-5.0 mm; Group 3, larger than 5 mm (from selfing). A total of 90 putative hybrid embryos were rescued using a highly enriched B5 medium to nourish the newly dissected embryos. The growing embryos were then placed in a high osmotic, modified B5 medium to induce maturation and dormancy. Schenk and Hildebrandt medium was used to germinate the dormant, partially dehydrated, physiologically mature embryos. Approximately 37% of the rescued embryos developed into plantlets in vitro, and approximately 8% grew into mature plants in the greenhouse. Morphological, cytological and isoenzyme patterns confirmed the hybrid status of all seven mature plants, all of which were generated using G. tomentella G 9943 as the paternal parent. It was observed that all soybean lines crossed with G 9943 were capable of producing mature hybrid plants. There was no correlation between the initial size of Group 2 seeds and plant survival rate. The hybrids were cloned by grafting and treated with colchicine. One of the treated plants displayed chromosome doubling.

Explants from 13-d old pepper (Capsicum annuum, L. cv. Early California Wonder) seedlings were cultured in Murashige and Skoog (MS) medium supplemented with different levels of 1-naphthalene acetic acid (NAA) and 6-benzylamino purine (BAP). Multiple shoot-buds proliferated from the cut surfaces of cotyledon, shoot-tip and hypocotyl explants in one month. The best NAA to BAP combinations (mg/l: mg/l) for multiple shoot-bud regeneration of the above three explant types were 0.1 ∶ 5.0, 0.0 ∶ 5.0, and 0.1 ∶ 10.0, respectively. Root explants did not express any new morphogenetic response in all hormonal combinations tested. Regenerated shoot-buds were excised from the explants and cultured in 1/2X or 1X MS medium supplemented with different levels of Indole-3-acetic acid (IAA) or NAA. When cultured in full strength MS medium with 0.5 mg/l IAA or 0.4 mg/l NAA, 70% of the buds rooted in one month. Plantlets were established successfully ex vitro under greenhouse mist and grown to maturity.

Fifty-two plant species, covering some Gymnosperms and all the key groups of Angiosperms, were chosen for surveying their intrinsic beta-glucuronidase-like activities. Histochemical (overnight incubation) and qualitative fluorometric (24 h incubation) assays indicated that, with few exceptions, such activities were detected in certain part(s) of the fruit walls, seed coats, endosperms or, especially, the embryos of the tested plants. Most of such activities in the excised immature embryos of soybean and string bean disappeared after one to a few days' in vitro culturing. Such activities in the intact mature seeds of these two species diminished also during germination process. The vegetative organs of seedlings/mature plants usually lack such activities. The enzyme(s) responsible for such activities was antigenically dissimilar to E. coli beta-glucuronidase.