Clonal Dissemination of Genetically Diverse Fluoroquinolone-Resistant Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli ST131 in a Veterans Hospital in Southern Taiwan

Uropathogenic Escherichia coli is the common pathogen to cause urinary tract infections (UTIs) and have become multidrug-resistant (MDR) extended-spectrum β-lactamase (ESBL) producers. The differences in the antimicrobial susceptibility, 5 bla genes, 12 virulence genes of 87 clinical ESBL-producing E. coli isolates and genomic variations and sequence types of 18 recurrent and repeated isolates from 9 patients were investigated. The 87 MDR-ESBL isolates collected mainly from indwelling urinary catheters (IUCs) and UTIs were highly resistant to fluoroquinolones, with over 50% of the isolates being resistant to cefepime and piperacillin/tazobactam and a few being resistant to carbapenem. These isolates carried at least two of the five bla genes examined, with the highest prevalence (87.4%) found for blaCTX-M (blaCTX-M3-like and blaCTX-M14-like), followed by blaCMY-2 (80.5%) and blaSHV (56.3%). The predominant virulence genes were the fimbriae gene fimH and the toxin genes cnf1 and hlyA in blood isolates and the capsule gene kpsMTII in UTI and blood isolates. Over 80% of the isolates carried yersiniabactin and aerobactin of siderophores. In 18 isolates, the fluoroquinolone-resistant ST131 isolate of pulsotypes I and II with blaCTX-M-15 was clonally disseminated in the hospital. The genomic plasticity of these ST131 occurred mainly through the conjugative plasmids with differences in replicon types A/C, I1, FIA, FIB and Y, size and number. In conclusion, MDR ESBL-producing E. coli isolates differed in virulence genes of UPEC and antibiotic resistance associated with the sources. Plasmid acquisition and chromosomal variations increase the spread of fluoroquinolone-resistant UPEC ST131 worldwide.

Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort

Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival times.Methods:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)apart.Exposures were baseline OPA,OPA changes,and baseline leisure-time physical activity.Results:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women occurred.Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same outcome.Baseline or changes in OPA showed no associations with CVD or cancer mortality.Conclusion:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women.Our longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.

Etiologies of Dyspepsia among a Chinese Population: One Hospital-Based Study

Background and Methods: Dyspepsia refers to a collection of upper gastrointestinal symptoms, and the causes may be either organic or functional. The aim of this study was to investigate the etiologies of dyspepsia among a Chinese population in Taiwan. Patients who underwent upper endoscopy for symptoms of dyspepsia were retrospectively analyzed between January and December 2008. Exclusion criteria included cirrhosis with varices, heart-burn sensation as the main symptom, gastrointestinal bleeding, hepatobiliary abnormalities, prior gastric surgery, and use of anti-acid medication for more than 2 months. Patients were classified according to the findings of upper endoscopy. Results: Data from the medical records of 2062 patients were collected and retrospectively analyzed. Normal endoscopic findings, gastritis, gastric ulcers, duodenal ulcers, reflux esophagitis and esophageal or gastric malignancy accounted for 1174 (56.9%), 215 (10.4%), 254 (12.3%), 194 (9.4%), 182 (8.8%) and 43 (2.1%) cases, respectively. The overall ratio of H. pylori infection was 28.4%. The ratio was the highest in duodenal ulcers and the lowest in reflux esophagitis. A significantly higher ratio of patients with gastric ulcers had a history of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) usage. Conclusion: Patients with organic dyspepsia, compared to those with functional dyspepsia, were older, male, and had a higher H. pylori infection ratio, a positive relationship with aspirin or NSAIDs usage, and more risk factors. These findings demonstrate that upper endoscopy has a high diagnostic yield in patients in this group.

Predicting portal venous anomalies by left-sided gallbladder or rightsided ligamentum teres hepatis: A large scale, propensity scorematched study

BACKGROUND Right-sided ligamentum teres(RSLT)is often associated with portal venous anomalies(PVA)and is regarded as a concerning feature for hepatobiliary intervention.Most studies consider RSLT to be one of the causes of left-sided gallbladder(LGB),leading to the hypothesis that LGB must always be present with RSLT.However,some cases have shown that right-sided gallbladder(RGB)can also be present in livers with RSLT.AIM To highlight the rare variation that RSLT may not come with LGB and to determine whether ligamentum teres(LT)or gallbladder location is reliable to predict PVA.METHODS This study retrospectively assessed 8552 contrast-enhanced abdominal computed tomography examinations from 2018 to 2021[4483 men,4069 women;mean age,59.5±16.2(SD)years].We defined the surrogate outcome as major PVAs.The cases were divided into 4 subgroups according to gallbladder and LT locations.On one hand,we analyzed PVA prevalence by LT locations using gallbladder location as a controlled variable(n=36).On the other hand,we controlled LT location and computed PVA prevalence by gallbladder locations(n=34).Finally,we investigated LT location as an independent factor of PVA by using propensity score matching(PSM)and inverse probability of treatment weighting(IPTW).RESULTS We found 9 cases of RSLT present with RGB.Among the LGB cases,RSLT is associated with significantly higher PVA prevalence than typical LT[80.0%vs 18.2%,P=0.001;OR=18,95%confidence interval(CI):2.92-110.96].When RSLT is present,we found no statistically significant difference in PVA prevalence for RGB and LGB cases(88.9%vs 80.0%,P>0.99).Both PSM and IPTW yielded balanced cohorts in demographics and gallbladder locations.The RSLT group had a significantly higher PVA prevalence after adjusted by PSM(77.3%vs 4.5%,P<0.001;OR=16.27,95%CI:2.25-117.53)and IPTW(82.5%vs 4.7%,P<0.001).CONCLUSION RSLT doesn't consistently coexist with LGB.RSLT can predict PVA independently while the gallbladder location does not serve as a sufficient predictor.

Rare combination of traumatic subarachnoid-pleural fistula and intracranial subdural hygromas:A case report

BACKGROUND Subarachnoid-pleural fistula(SPF)is a complex and rare condition characterized by a pathological shunt between the subarachnoid and pleural spaces.It can lead to the accumulation of cerebrospinal fluid(CSF)in the pleural space,pneumocephalus,and the development of central nervous system infection.Trauma or thoracic spinal surgery are common causes of SPF,with symptoms including postural headache,consciousness status changes,and dyspnea.The combination of SPF and subdural hygroma is a severe and rare condition,with little existing literature on its clinical correlation.CASE SUMMARY We report a case of an 83-year-old male patient with traumatic SPF and bilateral frontal subdural hygroma following a fall from height.The patient initially presented with severe lower back and buttock pain.During admission,the patient developed worsening lower limb weakness and pleural effusion.Further investigation revealed the presence of subdural hygromas with mass effect,requiring emergency bilateral subdural drainage.A multidisciplinary approach was undertaken to manage this complex condition,including intervention for hypovolemic CSF status and subdural hygroma management.The pleural effusion eventually resolved and the patient attained a higher level of con-sciousness after bilateral hygroma drainage surgery.We also reviewed the present literature relating to this rare combination of medical conditions.CONCLUSION Traumatic SPF with subsequent subdural hygroma is a rare but serious combination.Although the optimal treatment strategy for this complex condition remains uncertain,our literature review suggested that a multidisciplinary approach,including intervention for hypovolemic CSF and management of the subdural hygroma,is the most beneficial.

Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma:A literature review

Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first.

Risk factors and therapeutic response in Chinese patients with peptic ulcer disease

AIM:To assess the risk factors and the eff icacy of medications of patients with gastric and duodenal ulcers among Chinese patients in Taiwan.METHODS:Patients with peptic ulcers,diagnosed by upper endoscopy,were retrospectively collected between January 2008 and December 2008.The differences were compared.RESULTS:Among all 448 cases,254(56.6%) and 194(43.4%) patients had gastric ulcers and duodenal ulcers respectively.Patients with gastric ulcers were younger than those with duodenal ulcers.Although more men existed,there was a female predominance in middle-aged cases.Patients with duodenal ulcers had a higher rate of Helicobacter pylori(H.pylori) infection(62.4% vs 43.3%,P = 0.001),and those with gastric ulcers owned a significantly higher amount of aspirin and nonsteroidal anti-inflammatory drug(NSAID) use(7.5% vs 1.5%,6.7% vs 2.1%,P = 0.001).Tobacco smoking and alcohol drinking had no different impact between these two groups.Proton-pump inhibitors and H2-receptor antagonists(H2RA) were effective,but significantly less so in cases with duodenal ulcers receiving H2RAs,or in those with H.pylori infection and a history of NSAID use.CONCLUSION:Patients with gastric ulcers had lower H.pylori infection but more aspirin or NSAID use.Antisecretory therapy was ineffective in gastric ulcers underwent H2RA treatment,and cases combined H.pylori infection and NSAID use.

Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population

Background: Non-alcoholic fatty liver disease(NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese population.Methods: Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver(normal or NAFLD), and body mass index(BMI) levels(non-obese if BMI < 25 kg/m~2 or obese if BMI ≥ 25 kg/m~2).Results: There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver(group A), non-obese NAFLD(group B), obese normal liver(group C) and obese NAFLD(group D),respectively. The highest ratio of metabolic syndrome existed in the group B(26.9%), followed by group A(11.7%), group D(10.9%) and finally the group C(5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02) and glucose(OR = 1.02; 95% CI:1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases(adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals(OR = 2.81; 95% CI: 1.92–4.12).Conclusions: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.

Comparison of presentation and impact on quality of life of gastroesophageal reflux disease between young and old adults in a Chinese population

AIM:To compare the presentation and impact on qual-ity of life of gastroesophageal reflux disease(GERD)in old and young age groups.METHODS:Data from adult patients with GERD di-agnosed by endoscopic and symptomic characteristics were collected between January and November 2009.Exclusion criteria included combined peptic ulcers,ma-lignancy,prior surgery,antacid medication for more than 2 mo,and pregnancy.Enrolled patients were assigned to the elderly group if they were 65 years or older,or the younger group if they were under 65 years.They had completed the GERD impact scale,the Chinese GERD questionnaire,and the SF-36 question-naire.Data from other cases without endoscopic f ind-ings or symptoms were collected and these subjects comprised the control group in our study.RESULTS:There were 111 patients with GERD and 44 normal cases:78(70.3%)and 33 patients(29.7%)were in the younger and elderly groups,respectively.There were more female patients(60.3%)in the younger group,and more males(72.7%)in the elderly group.The younger cases had more severe and fre-quent typical symptoms than the elderly patients.Sig-nif icantly more impairment of daily activities was noted in the younger patients compared with the elderly group,except for physical functioning.CONCLUSION:Elderly patients with GERD were pre-dominantly male with rare presentation of typical symp-toms,and had less impaired quality of life compared with younger patients in a Chinese population.

The association of non-alcoholic fatty liver disease and metabolic syndrome in a Chinese population

BACKGROUND： Non-alcoholic fatty liver disease（NAFLD） is associated with features of metabolic syndrome. The aim of this study was to investigate the association between NAFLD and metabolic syndrome in a Chinese population. METHODS： Data from subjects were retrospectively collected from 2006 to 2009. The exclusion criteria included significant consumption of alcohol and chronic hepatitis B and C. The patients were assigned to two groups according to ultrasound findings： normal group and fatty liver group. The liver function of patients was determined by assessing serum alanine aminotransferase（ALT）. Metabolic syndrome was diagnosed based on the 2005 International Diabetes Federation criteria. RESULTS： A total of 7568 subjects were enrolled and 5736（75.8%） and 1832（24.2%） patients were assigned to the normal and fatty liver groups, respectively. The fatty liver group had significant male predominance（69.7% vs 56.0%）, higher body mass index（mean, 26.67 vs 23.55 kg/m^2） compared with the normal group. There were 441（7.7%） and 377（20.6%） cases with metabolic syndrome in the normal and fatty liver groups, respectively, with significant difference（P=0.001）, and the subgroup of 385 cases with fatty liver and elevated ALT had higher prevalence（28.8%） of metabolic syndrome. The strongest association of an individual component of metabolic syndrome with NAFLD was hyperlipidemia（adjusted OR=2.55, 95% CI： 2.22-2.94）.CONCLUSION： The individuals with NAFLD had a higher ratio of metabolic syndrome. Hyperlipidemia had the strongest positive association with NAFLD.

Heartburn and regurgitation have different impacts on life quality of patients with gastroesophageal reflux disease

AIM:To investigate the impact of heartburn and regurgitation on the quality of life among patients with gastroesophageal reflux disease(GERD).METHODS:Data from patients with GERD,who were diagnosed according to the Montreal definition,were collected between January 2009 and July 2010.The enrolled patients were assigned to a heartburn or a regurgitation group,and further assigned to an erosive esophagitis(EE)or a non-erosive reflux disease(NERD)subgroup,depending on the predominant symptoms and endoscopic findings,respectively.The general demographic data,the scores of the modified Chinese version of the GERDQ and the Short-form 36(SF-36)questionnaire scores of these groups of patients were compared.RESULTS:About 108 patients were classified in the heartburn group and 124 in the regurgitation group.The basic characteristics of the two groups were similar,except for male predominance in the regurgitation group.Patients in the heartburn group had more sleep interruptions(22.3%daily vs 4.8%daily,P=0.021),more eating or drinking problems(27.8%daily vs 9.7%daily,P=0.008),more work interferences(11.2%daily vs none,P=0.011),and lower SF-36 scores(57.68 vs64.69,P=0.042),than patients in the regurgitation group did.Individuals with NERD in the regurgitation group had more impaired daily activities than those with EE did.CONCLUSION:GERD patients with heartburn or regurgitation predominant had similar demographics,but those with heartburn predominant had more severely impaired daily activities and lower general health scores.The NERD cases had more severely impaired daily activity and lower scores than the EE ones did.

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma(HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

Impact of body mass index and gender on quality of life in patients with gastroesophageal reflux disease

AIM:To investigate the symptom presentation and quality of life in obese Chinese patients with gastroesophageal reflux disease(GERD).METHODS:Data from patients diagnosed with GERD according to the Montreal definition,were collected between January 2009 to March 2010.The enrolled patients were assigned to the normal [body mass index(BMI) < 25 kg/m 2 ],overweight(25-30 kg/m 2),and obese(BMI > 30 kg/m 2) groups.General demographic data,endoscopic findings,and quality of life of the three groups of patients were analyzed and compared.RESULTS:Among the 173 enrolled patients,102,56 and 15 patients were classified in the normal,overweight,and obese,respectively.There was significantly more erosive esophagitis(73.3% vs 64.3% vs 39.2%,P = 0.002),hiatal hernia(60% vs 33.9% vs 16.7%,P = 0.001),and males(73.3% vs 73.2% vs 32.4%,P = 0.001) in the obese cases.The severity and frequency of heartburn,not acid regurgitation,was positively correlated with BMI,with a significant association in men,but not in women.Obese patients were prone to have low quality of life scores,with obese women having the lowest scores for mental health.CONCLUSION:In patients with GERD,obese men had the most severe endoscopic and clinical presentation.Obese women had the poorest mental health.

Clinical significance of telomerase and its associate genes expression in the maintenance of telomere length in squamous cell carcinoma of the esophagus

AIM: To observe the interaction between the expression of telomerase activity (TA) and its associate genes in regulation of the terminal restriction fragment length(TRFL) in esophageal squamous cell carcinoma (SCC).METHODS: Seventy-four specimens of esophageal SCC were examined. The TA was measured by telomeric repeat amplification protocol (TRAP) assay, and the associated genes [human telomerase-specific reverse transcriptase (hTERT), hTERC, TP1, c-Myc, TRF1,and TRF2] were detected using RT-PCR method. The TRFL was measured by Telomere Length Assay Kit and Southern blotting. The correlations between the expression of telomerase and its associated genes with the TRFL and survivals were examined.RESULTS: Expressions of the TA, hTERT, hTERC, TP1,c-Myc, TRF1, and TRF2 genes were observed in 85.1%,64.9%, 79.7%, 100.0%, 94.6%, 82.4%, and 91.9% of the tumor tissues, respectively. The TRFL of the tumor and normal esophageal tissues were 2.70±1.42 and 4.93±1.74 kb, respectively (P＜0.0001). The TRFL of the telomerase positive and telomerase negative tumor tissues were 2.72±1.44 and 2.58±1.32 kb, respectively (P = 0.767).The TRFL ratios (TRFLR) of the telomerase positive and telomerase negative tumor tissues were 0.55±0.22 and 0.59±0.41, respectively (P = 0.742). The expression rates of h-TERT (P = 0.0002), hTERC (P＜0.0001), and TRF1(P = 0.002) in the tumor tissues are higher than those of the normal paired tissues. Though TA is markedly activated in tumor tissues (P＜0.0001), its expression is not related to clinicopathological parameters including gender, tumor differentiation, and TNM stages. The cumulative 4-year survival rates of telomerase positive and telomerase negative cases were 35.86% and 31.2%,respectively (P = 0.8442). The cumulative 4-year survival rates of patients with their TRFLR ≤85% and ＞85%were 38.7% and 15.7%, respectively (P = 0.1307).CONCLUSION: Though telomerase expression is not related to tumor stages and prognosis, our data support that the TA increased as the TRFL decreased,probably under the control of hTERT, hTERC, and TRF1.When telomerase expression was activated, only TRF2overexpression persisted to stabilize T-loop formation.Furthermore, as the TRFLR decreased to 85%, a trend of better prognosis was observed. Cox model analysis indicates a higher t/n TRFLR and distant metastasis are independent poorer prognostic factors (P = 0.035 and P = 0.042, respectively).

Current systemic treatment of hepatocellular carcinoma:A review of the literature

Hepatocellular carcinoma(HCC) is the fifth most common form of human cancer worldwide and the third most common cause of cancer-related deaths. The strategies of various treatments for HCC depend on the stage of tumor,the status of patient's performance and the reserved hepatic function. The Barcelona Clinic Liver Cancer(BCLC) staging system is currently used most for patients with HCC. For example,for patients with BCLC stage 0(very early stage) and stage A(early stage) HCC,the curable treatment modalities,including resection,transplantation and radiofrequency ablation,are taken into consideration. If the patients are in BCLC stage B(intermediate stage) and stage C(advanced stage) HCC,they may need the palliative transarterial chemoembolization and even the target medication of sorafenib. In addition,symptomatic treatment is always recommended for patients with BCLC stage D(end stage) HCC. In this review,we will attempt to summarize the historical perspective and the current developments of systemic therapies in BCLC stage B and C in HCC.

Prostatic abscess of Klebsiella pneumoniae complicating septic pulmonary emboli and meningitis: A case report and brief review

Prostatic abscess is a rare entity with an incidence of 0.5% to 2.5% in all prostate diseases and usually occurs in the 5th and 6th decades of life with immunocompromised status,Prostatic abscess might be a process of evolution from acute prostatitis,Klebsiella pneumoniae is the leading microorganism in the diabetic patients of prostatic abscess in Taiwan,A 60-year-old diabetic man,with a one-week history of acute bacterial prostatitis was reported in this study,presenting to the emergency department with sudden altered mental status,The abdominal computed tomographic scan demonstrated lobulated prostatic abscess and multiple septic pulmonary emboli with lung abscesses,Analysis of cerebrospinal fluid showed white blood cells of 10 771 counts/mm3 with segmented neutrophils of 99%,Cultures of blood,cerebrospinal fluid and sputum yielded Klebsiella pneumoniae,We concluded that computed tomographic scan can make a definite diagnosis of prostatic abscess associated with complications and management with empiric antibiotics and adequate drainage is suggested.

Lower serum folate is associated with development and invasiveness of gastric cancer

AIM: To evaluate the associations of serum folate levelwith development, invasiveness and patient survival of gastric cancer. METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls(3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender(all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population(OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata(age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years(OR = 21.67, 95%CI: 8.27-56.80), males(OR = 17.95, 95%CI: 7.93-40.62), and females(OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion(OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion(OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis(OR =6.67, 95%CI: 1.28-34.91) of gastric cancer(all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival(HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.

Risks of rapid decline renal function in patients with type 2 diabetes

Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general,it is defined by the decrease of estimated glomerular filtration rate(e GFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained declinein e GFR of > 5 m L/min per 1.73 m2 per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection.

机器人辅助腹腔镜根治前列腺切除术的外科学习曲线：一名外科医生500病例的经验

To analyze the learning curve for cancer control from an initial 250 cases （Group I） and subsequent 250 cases （Group II） of robotic-assisted laparoscopic radical prostatectomy （RALP） performed by a single surgeon. Five hundred consecutive patients with clinically localized prostate cancer received RALP and were evaluated. Surgical parameters and perioperative complications were compared between the groups, Positive surgical margin （PSM） and biochemical recurrence （BCR） were assessed as cancer control outcomes. Patients in Group II had significantly more advanced prostate cancer than those in Group I （22.2% vs 14.2%, respectively, with Gleason score 8-10, P = 0.033; 12.8% vs 5.6%, respectively, with clinical stage T3, P = 0.017）. The incidence of PSM in pT3 was decreased significantly from 49% in Group I to 32.6% in Group Ih A meaningful trend was noted for a decreasing PSM rate with each consecutive group of 50 cases, including pT3 and high-risk patients. Neurovascular bundle （NVB） preservation was significantly influenced by the PSM in high-risk patients （84.1% in the preservation group vs 43.9% in the nonpreservation group）. The 3-year, 5-year, and 7-year BCR-free survival rates were 79.2%, 75.3%, and 70.2%, respectively. In conclusion, the incidence of PSM in pT3 was decreased significantly after 250 cases. There was a trend in the surgical learning curve for decreasing PSM with each group of 50 cases. NVB preservation during RALP for the high-risk group is not suggested due to increasing PSM.

Thymoquinone suppresses migration of Lo Vo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce Lo Vo cancer cell growth. Cyclooxygenase 2(COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2(PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoV o cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.