The Impact of Relative Humidity and Atmospheric Pressure on Mortality in Guangzhou, China

Objective Although many studies have examined the effects of ambient temperatures on mortality, little evidence is on health impacts of atmospheric pressure and relative humidity. This study aimed to assess the impacts of atmospheric pressure and relative humidity on mortality in Guangzhou, China. Methods This study included 213,737 registered deaths during 2003-2011 in Guangzhou, China. A quasi-Poisson regression with a distributed lag non-linear model was used to assess the effects of atmospheric pressure/relative humidity. Results We found significant effect of low atmospheric pressure/relative humidity on mortality. There was a 1.79%(95% confidence interval: 0.38%-3.22%) increase in non-accidental mortality and a 2.27%(0.07%-4.51%) increase in cardiovascular mortality comparing the 5th and 25 th percentile of atmospheric pressure. A 3.97%(0.67%-7.39%) increase in cardiovascular mortality was also observed comparing the 5th and 25 th percentile of relative humidity. Women were more vulnerable to decrease in atmospheric pressure and relative humidity than men. Age and education attainment were also potential effect modifiers. Furthermore, low atmospheric pressure and relative humidity increased temperature-related mortality. Conclusion Both low atmospheric pressure and relative humidity are important risk factors of mortality. Our findings would be helpful to develop health risk assessment and climate policy interventions that would better protect vulnerable subgroups of the population.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy

BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.

Prostate volume as an independent predictor of prostate ：ancer in men with PSA of 10-50 ng ml-1

前列腺体积(PV ) 被显示了与察觉在 ‘ 与前列腺特定的抗原(PSA ) 在人评估的前列腺癌症(PCa ) 被联系；灰 zone'(2.0-10.0 ； ng ml −1) 。然而， PSA ‘；因为在亚洲人的 PCa 的发生是相对低的，在亚洲人的灰 zone' 应该更高。因此，我们与测量 10-50 的 PSA 在人评估了在 PV 和 PCa 察觉率之间的协会； ng ml −1 。与 PV 文档经历了 13 核心 prostatic 活体检视的人参予了学习。multivariate 逐步的回归被用来评估在前列腺活体检视的时间的 PV 是否能预言 PCa 的风险。在在不同 PSA 范围的人之中的 PCa 的率，由 PV medians 成层(<； 60 并且 ≥； 60 ； ml ) ，被计算。有 261 个人，总之包括。PV 是 PCa 风险的最强壮的预言者(机会比率， 0.02；P<； 0.001 ) 与另外的变量相比。在有测量 < 的 PV 的人的 PCa 率； 60 并且 ≥； 60 ；在 10-19.9 的 ml； ng ml −1 PSA 组是 40.6 %；并且 15.1 %；，分别地当时为有测量 20-50 的 PSA 的人的率； ng ml −1 是 65.1 %；并且 26.8 %；。PV 是在有测量 10-50 的 PSA 的人的 PCa 的一个独立预言者； ng ml −1 。在临床的实践，特别地为有 PCa 的更低的发生的那些国家，当时， PV 应该被考虑有测量 10-50 的 PSA 的 counselling 病人；关于他们的 PCa 风险的 ng ml −1 。

Regulating effect of glycyrrhetinic acid on bronchial asthma smooth muscle proliferation and apoptosis as well as inflammatory factor expression through ERK1/2 signaling pathway

Objective: To study the influence of glycyrrhetinic acid(GA) on bronchial asthma(BA)smooth muscle proliferation and apoptosis as well as inflammatory factor expression and its molecular mechanism.Methods: Male SD guinea pigs were selected and made into asthma models, bronchial asthma smooth muscle cells were cultured and divided into BA group, GA group and GA + LM group that were treated with serum-free RPMI1640 culture medium, serumfree RPMI1640 culture medium containing 50 ng/mL glycyrrhetinic acid, serum-free RPMI1640 culture medium containing 50 ng/mL glycyrrhetinic acid and 100 ng/mL LM22B-10 respectively; normal guinea pigs were collected and bronchial smooth muscle cells were cultured as control group. The cell proliferation activity as well as the expression of proliferation and apoptosis genes, inflammatory factors and p-ERK1/2 was determined.Results: Proliferation activity value and m RNA expression of Bcl-2, TNF-α, IL-4, IL-6,YKL-40, protein expression of p-ERK1/2 of airway smooth muscle cell in BA group were significantly higher than those of control group while m RNA expression levels of Bax,caspase-9 as well as caspase-3 were significantly lower than that of control group(P < 0.05); proliferation activity value and m RNA expression of Bcl-2, TNF-α, IL-4, IL-6, YKL-40, protein expression of p-ERK1/2 of airway smooth muscle cell in GA group were significantly lower than those of BA group(P < 0.05) while the m RNA expression levels of Bax, caspase-9 as well as caspase-3 were significantly higher than those of BA group(P < 0.05); proliferation activity value and m RNA expression of Bcl-2, TNF-α, IL-4, IL-6, YKL-40 of airway smooth muscle cell in GA + LM group were significantly higher than those of GA group(P < 0.05) while m RNA expression levels of Bax, caspase-9 as well as caspase-3 were significantly lower that of GA group(P < 0.05).Conclusion: GA can inhibit the proliferation of bronchial smooth muscle cells and reduce the expression of inflammatory factors by inhibiting the phosphorylation of ERK1/2.

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model

Objective: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion(PNI) in colorectal cancer(CRC).Methods: After computed tomography(CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort(346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen(CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation(separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results: The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index(c-index): 0.817; 95% confidence interval(95% CI): 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination(c-index: 0.803; 95% CI: 0.794–0.812).Conclusions: Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

AIM: To detect the expression of fragile histidine triad (FHIT) in normal colorectal tissue, colorectal adenoma and colorectal cancer (CRC) tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associated proteins (Bcl-2, Bax, survivin) and apoptosis in colorectal cancer. METHODS: FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction (RT-PCR) assay. Tissue microarray (TMA) was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid (PPH) tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens. RESULTS: Ten out of 26 (38.5%) CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matchednormal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins (Bax, Bcl-2 and survivin) in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosis- associated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT positive tumors (5.41 ± 0.23 vs 0.56 ± 0.10, P < 0.01). CONCLUSION: The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

AIM:To investigate the anti-tumor effects of combined cytotoxic drug(gemcitabine)and photodynamic therapy(PDT)on human pancreatic cancer xenograft in nude mice. METHODS:Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice.Sixty mice were randomly allocated into a control group(without treatment),photosensitizer treatment group(2 mg/kg photosan,without illumination),chemotherapy group (50 mg/kg gemcitabine i.p.),PDT group(2 mg/kg photosan+laser irradiation)and combined treatment group(photosan+chemotherapy),with 12 mice in each group.Tumor size was measured twice every week.Anti-tumor activity in different groups was evaluated by tumor growth inhibition(TGI). RESULTS:No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group.PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy (0.24±0.15-0.49±0.08 vs 0.43±0.18-1.25± 0.09,P<0.05).PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group(0.12±0.07-0.28 ±0.12 vs 0.39±0.15-1.20±0.11,P<0.05),small dose chemotherapy group(0.12±0.07-0.28±0.12 vs 0.32±0.14-1.16±0.08,P<0.05)and control group (0.12±0.07-0.28±0.12 vs 0.43±0.18-1.25±0.09, P<0.05).TGI was higher in the combined treatment group(82.42%)than in the PDT group(58.18%). CONCLUSION:PDT has a significant anti-tumor effect,which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer

Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.

Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo

AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance.

Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.

Therapeutic advances in non-alcoholic fatty liver disease:A microbiota-centered view

Non-alcoholic fatty liver disease(NAFLD)is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide,especially in the West.There are no drugs available at present to treat NAFLD,and the primary therapeutic options include weight loss and the combination of healthy diet and exercise.Therefore,novel interventions are required that can target the underlying risk factors.Gut microbiota is an“invisible organ”of the human body and vital for normal metabolism and immuno-modulation.The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus,and is most abundant in the intestine.Since dysregulated gut microbiota is an underlying pathological factor of NAFLD,it is a viable therapeutic target that can be modulated by antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation,and microbial metabolites.In this review,we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies,and critically evaluate novel targets and strategies for treating NAFLD.

Evaluation of human epidermal growth factor receptor 2 status of breast cancer using preoperative multidetector computed tomography with deep learning and handcrafted radiomics features

Objective:To evaluate the human epidermal growth factor receptor 2(HER2)status in patients with breast cancer using multidetector computed tomography(MDCT)-based handcrafted and deep radiomics features.Methods:This retrospective study enrolled 339 female patients(primary cohort,n=177;validation cohort,n=162)with pathologically confirmed invasive breast cancer.Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase.After the feature selection procedures,handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis.Performance was assessed by measures of discrimination,calibration,and clinical usefulness in the primary cohort and validated in the validation cohort.Results:The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739[95%confidence interval(95%CI):0.661-0.818]in the primary cohort and 0.695(95%CI:0.609-0.781)in the validation cohort.The deep radiomics signature also had a discriminative ability with a C-index of 0.760(95%CI:0.690-0.831)in the primary cohort and 0.777(95%CI:0.696-0.857)in the validation cohort.The combined model,which incorporated both the handcrafted and deep radiomics signatures,showed good discriminative ability with a C-index of 0.829(95%CI:0.767-0.890)in the primary cohort and 0.809(95%CI:0.740-0.879)in the validation cohort.Conclusions:Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer.Thus,these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.

World Journal of GastroenterologyDevelopment and validation of a risk prediction score for the severity of acute hypertriglyceridemic pancreatitis in Chinese patients

BACKGROUND The frequency of acute hypertriglyceridemic pancreatitis(AHTGP) is increasing worldwide. AHTGP may be associated with a more severe clinical course and greater mortality than pancreatitis caused by other causes. Early identification of patients with severe inclination is essential for clinical decision-making and improving prognosis. Therefore, we first developed and validated a risk prediction score for the severity of AHTGP in Chinese patients.AIM To develop and validate a risk prediction score for the severity of AHTGP in Chinese patients.METHODS We performed a retrospective study including 243 patients with AHTGP. Patients were randomly divided into a development cohort(n = 170) and a validation cohort(n = 73). Least absolute shrinkage and selection operator and logistic regression were used to screen 42 potential predictive variables to construct a risk score for the severity of AHTGP. We evaluated the performance of the nomogram and compared it with existing scoring systems. Last, we used the best cutoff value(88.16) for severe acute pancreatitis(SAP) to determine the risk stratification classification.RESULTS Age, the reduction in apolipoprotein A1 and the presence of pleural effusion were independent risk factors for SAP and were used to construct the nomogram(risk prediction score referred to as AAP). The concordance index of the nomogram in the development and validation groups was 0.930 and 0.928, respectively. Calibration plots demonstrate excellent agreement between the predicted and actual probabilities in SAP patients. The area under the curve of the nomogram(0.929) was better than those of the Bedside Index of Severity in AP(BISAP), Ranson, Acute Physiology and Chronic Health Evaluation(APACHE II), modified computed tomography severity index(MCTSI), and early achievable severity index scores(0.852, 0.825, 0.807, 0.831 and 0.807, respectively). In comparison with these scores, the integrated discrimination improvement and decision curve analysis showed improved accuracy in predicting SAP and better net benefits for clinical decisions. Receiver operating characteristic curve analysis was used to determine risk stratification classification for AHTGP by dividing patients into high-risk and low-risk groups according to the best cutoff value(88.16). The high-risk group(> 88.16) was closely related to the appearance of local and systemic complications, Ranson score ≥ 3, BISAP score ≥ 3, MCTSI score ≥4, APACHE II score ≥ 8, C-reactive protein level ≥ 190, and length of hospital stay.CONCLUSION The nomogram could help identify AHTGP patients who are likely to develop SAP at an early stage, which is of great value in guiding clinical decisions.

Clinical Characteristics of Sleep Disorders in Patients with Parkinson's Disease

In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease(PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index(PSQI), and the Epworth Sleepiness Scale(ESS). It was found that poor sleep quality(77.11%) and excessive daytime sleepiness(32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency(SE) was significantly decreased(P<0.01), and sleep latency(SL) and the arousal index(AI) were increased(P<0.05) in the PD group as compared with those in the control group. SE and total sleep time(TST) were positively correlated with the Hoehn and Yahr(H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group(P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

Study on Treatment of Polycystic Ovarian Syndrome with Infertility by Combined Therapy of Chinese Herbal Medicine and Compound Cyproterone Acetate

Objective: To evaluate the effect of combined therapy of Chinese herbal medicine and compound cyproterone acetate (CPA) in treating non-obesity polycystic ovarian syndrome (PCOS) and to explore its mechanism in improving withdrawal ovulation. Methods:Eighty-six patients of non-obesity PCOS, typed as Shen-deficiency with blood stasis Syndrome or Shen-deficiency with Phlegm-Dampness Syndrome by Syndrome Differentiation in traditional Chines medicine, were randomly divided into three groups: (1) The TCM group (n=26) was treated with Chinese drugs for 6 menstrual cycles; (2) The western medicine (WM) group (n=30) was treated with 1 tablet of CPA for 21 days, with the treatment beginning from the 5th day of menstruation. The treatment was given for 3 menstrual cycles by repetitious medication, which stopped and restarted on the 5th day of withdrawal bleeding. Then the ovulation promoting therapy was applied by using clomifene citrate and human chorionic gonadotropin (CC/Hcg) for 3 menstrual cycles; (3) The TCM-WM group (n=30) was treated with the medications used for the above two groups. The menstrual cycle, the volume and duration of the menstruation, as well as the improvement of acne and pilosis [Ferriman-Gallway (F-G) scoring]were observed after 3 cycles ended. Moreover, condition of ovulation was monitored by B-ultrasonography at the 4th-6th cycle and status of pregnancy was observed. Results: Compared with before treatment, the blood level of luteinizing hormone (LH) and testosterone (T) in all 3 groups after treatment significantly decreased (P<0.05), with its ratio to follicle-stimulating hormone (LH/FSH) recovered to normal, but without markedly change in levels of FSH, estradiol (E2) and prolactin (PRL). The menstrual cycle in most patients got regular and acne significantly alleviated (P<0.05), and the improvement of infrequent menstruation and acne was better in the WM group and the TCM-WM group than that in the TCM group, but pilosis showed no significant improvement in all three groups. The periodical ovulation rate in the TCM-WM group (73.1%) and the WM group (68.3%) was significantly higher than that in the TCM group (40%). The pregnancy rate in the TCM-WM group (53.8%) was significantly higher than that in the other two groups (26.1% and 25% respectively, all P<0.05). Conclusion: Using combined therapy of TCM and composite CPA followed by ovulation promoting agents of TCM and WM to treat patients of non-obesity PCOS could relieve the clinical symptoms, improve the abnormal blood level of sex hormones and significantly elevate the pregnancy rate.

Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans

AIM:To investigate the association of polymorphisms of nur-related receptor 1 (Nurr1 ) and development of alcohol dependence in Mexican Americans. METHODS:Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Americans; these two groups were sex-and age-matched. Sample DNA was extracted and genomic DNA was amplified by polymerase chain reaction. The-2922(C) 2-3 polymerase chain reaction products were digested with Sau96I , alleles of 1345(G/C) , and -1198(C/G) in the regulatory region as well as Ex+132 (G/T/A/C) and Ex+715(T/-) in exon 3 were studied by sequencing. RESULTS:The C2/C2, C2/C3, C3/C3 genotype distribution of -2922(C) 2-3 was 34.4%, 38.2% and 27.5% inthe nonalcoholic group compared to 23.3%, 51.2% and 25.4% in the alcoholic group (P = 0.001). The C/C, C/G, G/G genotype distribution of -1198(C/G) was 23.5%, 46.1% and 30.3% in the nonalcoholic group compared to 13.9%, 50.9% and 35.3% in the alcoholic group (P = 0.007). However, the -1345 (G/C) , Ex3+132(G/T/A/C) and Ex3+715(T/-) alleles were not polymorphic in Mexican Americans, and all those studied had G/G, G/G and T/T genotype for these three alleles, respectively. The -2922(C) 2-3 did not show allele level difference between alcoholic and nonalcoholic individuals, but -1198 (C/G) showed a significant allele frequency difference between alcoholic (39.3%) and nonalcoholic (46.6%) populations (P = 0.005). Excluding obese individuals, significant differences were found at both genotypic and allelic levels for the -2922(C) 2-3 polymorphism (P = 0.000 and P = 0.049) and the -1198 (C/G) polymorphism (P = 0.008 and P = 0.032) between nonobese alcoholics and nonobese controls. Excluding smokers, a significant difference was found only at the genotypic level for the -2922(C) 2-3 polymorphism (P = 0.037) between nonsmoking alcoholics and nonsmoking controls, but only at the allelic level for the -1198(C/G) polymorphism (P = 0.034). CONCLUSION:Polymorphisms in the regulatory region of Nurr1 are implicated in pathogenesis of alcohol dependence and the Nurr1 /dopamine signaling pathway might be important for this dependence development in Mexican Americans.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Percutaneous transcatheter super-selective renal arterial embolization with N-butyl cyanoacrylate for iatrogenic renal hemorrhage

Background:To evaluate the safety and efficacy of percutaneous transcatheter super-selective renal arterial embolization(SRAE)with N-butyl cyanoacrylate(NBCA)for iatrogenic renal hemorrhage.Methods:Between January 2014 and December 2019,45 patients(including 18 patients with coagulopathy),who underwent percutaneous transcatheter SRAE with NBCA for iatrogenic renal hemorrhage at our institution,were retrospectively reviewed.The technical success rate,clinical success rate,and embolization-related complications were analyzed.The values of estimated glomerular filtration rate(eGFR),serum creatinine(sCr),and serum urea(sUr)were analyzed at the time of pre-SRAE,post-SRAE,and last follow-up to evaluate the effects of NBCA-based SRAE on renal function.Results:Diagnostic renal arteriography revealed contrast extravasation in 18 patients and pseudoaneurysms in 27 patients.NBCA mixed with iodized oil in a 1:2–1:4 ratio was the sole embolic agent.No procedure-related mortality or major complications occurred.The technical and clinical success rates were both 100%.The values of eGFR,sCr and sUr were not found to be significantly different between pre-SRAE,post-SRAE and last follow-up(eGFR:91.52±21.17 vs.90.98±22.11 vs.92.14±23.51 mL/min/1.73 m^(2),p=0.729;sCr:74.73±11.08 vs.75.27±12.43 vs.73.95±10.14μmol/L,p=0.543;sUr:5.69±0.84 vs.5.71±0.96 vs.5.70±0.79,p=0.515,respectively).Conclusions:Percutaneous transcatheter SRAE with NBCA is a safe and effective treatment modality for iatrogenic renal hemorrhage with no deterioration of renal function.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease

Objective Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease(TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. Methods We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. Results A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level(≤ 102.0 mmol/L) or serum sodium level(≤ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death(hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention(PCI) with Taxus and Cardiac Surgery score. Conclusion Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.