Selenga River human dispersal path in Initial Upper Paleolithic

Here,we consider earlier Upper Paleolithic sites in the Selenga River Basin,the main fluvial input of Lake Baikal that flows through northern Mongolia and the southwestern Transbaikal region of Russia.Lithic industries from these sites can be attributed to the laminar Initial Upper Paleolithic(IUP)technocomplex,widespread in southern Siberia and Central Asia.IUP industries appear in the Selenga Basin about 45 kaBP cal.Aspects of regional typological variability and the transport of exotic raw materials over long distances indicate that these populations participated in developed exchange networks and employed high mobility targeting the acquisition of necessary raw materials.Two site types are present:quarry-workshops in northern Mongolia and generalized activity settlements in the southwestern Transbaikal.Although faunal data are limited,we interpret available information as indicating a specialization on hunting,focusing on migrating steppe game species.The distribution of sites in the mid-altitudes and landscapes of the Selenga-Orkhon geographical region and the geomorphological homogeneity of this territory also supported interregional human moves during the IUP.

On the beginning of the Japanese Upper Paleolithic:A review of recent archaeological and anthropological evidence

The beginning of the Japanese Upper Paleolithic has mainly been examined using two major models:the Middle Paleolithic evolutionary model within the archipelago and the continental Upper Paleolithic diffusion/migration model.However,recent archeological data from Japan and nearby countries are challenging such simple models.This paper critically reviews previous chronology of the Japanese Paleolithic,including possible Lower and Middle Paleolithic(LP/MP),and attempts to show an alternative model of the beginning of the Japanese Upper Paleolithic.This paper suggests several possible specimens of LP/MP and recommends further geoarchaeological investigation to understand the reliability and cultural relationship between possible LP/MP specimens and the Early Upper Paleolithic(EUP).The start of the Japanese EUP is presently characterized by a flake industry with trapezoids and denticulates around 39-37 kaBP cal on Paleo-Honshu Island,which has partial resemblance with contemporary assemblages in China and the Korean Peninsula,although trapezoids are endemic only to the Japanese EUP and may have derived from the ancestral lithic tradition.Blade technology appeared earliest on Central Paleo-Honshu Island,about 1000 years later than the earliest flake technology.Although blade technology may have originated from the elongated flake technology of the previous period,the sudden simultaneous emergence implies that it diffused from the Korean Peninsula.This paper proposes that blade technology from the Korean Peninsula arrived on the northeastern Paleo-Honshu Island,including the Japan Sea coastal region of western Honshu,rather than the southwest,where flake technology long prospered,due to differences in ecological settings and adaptation strategies between the two regions.

探究晚期恶性肿瘤患者接受替吉奥胶囊姑息治疗的生存情况

目的:探讨晚期大肠癌患者选用替吉奥胶囊姑息治疗的价值。方法:择取2017年6月-2019年6月佛山市三水区人民医院收治的晚期大肠癌患者40例,依随机信封法均分为两组,对照组20例选用安慰剂治疗,观察组20例选用替吉奥胶囊姑息治疗,统计对比两组生存期、近期临床总有效率、血清水平。结果:观察组近期临床总有效率(85.00%)高于对照组(50.00%),差异有统计学意义(P<0.05);观察组生存期高于对照组,差异有统计学意义(P<0.05);观察组血清水平低于对照组,数据对比(P<0.05)。结论:将替吉奥胶囊应用在晚期大肠癌患者姑息治疗中可提高近期临床总有效率,延长无进展生存期,值得借鉴。

Advances in Toxicology of Nε-(carboxymethyl)-lysine(CML)

Advanced glycation end-products （AGEs） are products of non-enzymatic glycation of proteins, lipids or nucleic acids and other macromolecules. To be spe- cific, Nε-（carboxymethyl）-Iysine （CML） is one of the most important components of AGEs, which is wildly distributed in the body and can be formed in vivo or in food processing and heating processes. Previous studies have shown that CML is a ma- jor immunological epitope in AGEs and plays an important role in diabetes and its complications, as well as in the development and progression of aging. This review summarized recent advances in major source, toxicological hazard and control mea- sures of CML.

Study on Seedling Quality of Double-cropping Late Rice Sowed at Different Dates in Guangdong

[Objective] The aim was to study seedling quality of rice sowed at different dates so as to provide theoretical basis for determining the best seeding time.[Method] By investigating the characters of shoot and root of different varieties sowed at different dates,the best seeding time of double-cropping late rice was determined.[Result] The first leaf sheath height and the second leaf length shared significantly positive correlation,which fit the quadratic equation well.The effects of different sowing dates on shoot and root of three rice varieties appeared significant difference.[Conclusion] The best seeding time of Tianyou428 was in June 25-July 2 and that of Tianyou998 and Yuxiangyouzhan was in July 2-9.

Comparison of Letrozole and Aminoglutethimide in Treatment of 113 Cases of Postmenopausal Women with Advanced Breast Cancer

Objective: To compare the efficacy and tolerability of letrozole with aminoglutethimide (AG) in postmenopausal women with advanced breast cancer. Methods: The multicenter, randomized controlled clinical trial was conducted in 113 patients. They randomly received letrozole 2.5 mg once daily (letrozole group) or AG 250 mg 4 times daily (AG group) with hydrocortisone. Results: The OR in letrozole group was 23.73% (2 cases of CR and 12 cases of PR, ITT OR was 21.88%), which was higher than in AG group (the OR 11.11%, 1 CASE of CR and 5 cases of PR, ITT 10.17%), but there was no statistically significant difference (P>0.05). Adverse events (AE) and the treatment related AE (RAE) in letrozole group (n=59) was 18.54% and 13.56% respectively, significantly lower than those (42.11% and 33.33% respectively) in AG group (n=57, P=0.002). Conclusion: The OR of letrozole in the treatment of postmenopausal advanced breast cancer positive or unknown for hormonal receptor is 23.73%, showing no significant difference to that of AG. The AE of letrozole are significantly less than AG.

Clinical Benefit with Intraoperative Radiotherapy Combined with Regional Chemotherapy for Advanced Pancreatic Carcinoma

Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic adenocarcinoma were treated with IORT and regional chemotherapy with 5-FU, Epirubucin and Mitomycin, and 6 cases accepted external radiotherapy postoperatively.Results: 35.29% (6/17) of the patients were clinical benefit responders and 23.53% (4/17) had a partial response. The median survival time was 11 months and the 1-year survival rate was 35.29% (6/17)Conclusion: IORT in combination with regional chemotherapy had a good impact on clinical benefit without severe side effects in locally advanced pancreatic carcinoma and led to a significant prolongation of the survival time. Key words pancreatic cancer - intraoperative radiotherapy - chemotherapy

Effect of Different Seedling Age on the Growth and Yield of Double Cropping of Late Rice

The study aims to solve the problems of late transplanting rice with differ- ent seedling ages at the lower reaches of Yangtze River. We selected six varieties of different thermal and photo-response characteristics as the test material to study the effect of different seedling ages on growth and yield of rice. The results showed that growing period of thermal-response rice was delayed by long seedling age, but less affected by the impact of photo-response rice; the yield of later thermal-re- sponse varieties with 25 days and 30 days seedling ages was significantly reduced. In contrast, the yield of early thermal-response varieties and later photo-response varieties were significantly reduced with 30 days seedling age. The optimal trans- planting seedling age was 15 days of thermal-response rice, while photo-response rice was 20 days. The thermal-response rice should be selected as early maturing varieties, while the photo-response rice could be selected as late maturing varieties for high yield.

MELD vs Child-Pugh and creatinine-modified Child-Pugh score for Dredicting survival in patients with decompensated cirrhosis

AIM: Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive values of MELD, Child-Pugh and creatinine modified Child-Pugh scores in decompensated cirrhosis. METHODS: A cohort of 102 patients with decompensated cirrhosis followed-up for a median of 6 mo was studied.Two types of modified Child-Pugh scores estimated by adding 0-4 points to the original score using creatinine levels as a sixth categorical variable were evaluated.RESULTS: The areas under the receiver operating characteristic curves did not differ significantly among the four scores, but none had excellent diagnostic accuracy (areas:0.71-0.79). Child-Pugh score appeared to be the worst, while the accuracy of MELD was almost identical with that of modified Child-Pugh in predicting short-term and slightly better in predicting medium-term survival. In Cox regression analysis, all four scores were significantly associated with survival, while MELD and creatinine-modified Child-Pugh scores had better predictive values (c-statistics: 0.73 and 0.69-0.70) than Child-Pugh score (c-statistics: 0.65). Adjustment for gamma-glutamate transpeptidase levels increased the predictive values of all systems (c-statistics: 0.77-0.81). Analysis of the expected and observed survival curves in patients subgroups according to their prognosis showed that all models fit the data reasonably well with MELD probably discriminating better the subgroups with worse prognosis. CONCLUSION: MELD compared to the old Child-Pugh and particularly to creatinine-modified Child-Pugh scores does not appear to offer a clear advantage in predicting survival in patients with decompensated cirrhosis in daily clinical practice.

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

New perspectives in the treatment of advanced or metastatic gastric cancer

Metastatic gastric cancer remains an incurable disease,with a relative 5-year survival rate of 7%-27%.Chemotherapy,which improves overall survival(OS) and quality of life,is the main treatment option.Metaanalysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine,an anthracycline,and cisplatin(ECF).Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens,the availability of newer agents has provided some measure of optimism.A number of new combinations incorporating docetaxel,oxaliplatin,capecitabine,and S-1 have been explored in randomized trials.Some combinations,such as epirubicin-oxaliplatin-capecitabine,have been shown to be as effective as(or perhaps more effective than) ECF,and promising early data have been derived for S-1 in combination with cisplatin.One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments.However,the biggest hope for signif icant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy f irst-line regimens.

Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer?

AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.

Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

Advanced gastric cancer:Is there enough evidence to call second-line therapy standard?

Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.

Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer: Which is superior?

The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy are controversial topics. The MEDLINE, Cochrane Library databases, and meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer. Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy. Neither adjuvant or neoadjuvant radiotherapy impacts overall survival. Short course versus long course neoadjuvant radiotherapy remains controversial. There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery. Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity. Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy, and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation. Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer. There are significant side effects from radiation, including anorectal and sexual dysfunction, which may be less with short course neoadjuvant radiation.

Child-Pugh-Turcott versus Meld score for predicting survival in a retrospective cohort of black African cirrhotic patients

AIM: To compare the performance of the Child-Pugh-Turcott (CPT) score to that of the model for end-stage liver disease (MELD) score in predicting survival of a retrospective cohort of 172 Black African patients with cirrhosis on a short and mid-term basis.METHODS: Univariate and multivariate (Cox model) analyses were used to identify factors related to mortality. Relationship between the two scores was appreciated by calculating the correlation coefficient. The Kaplan Meier method and the log rank test were used to elaborate and compare survival respectively. The Areas Under the Curves were used to compare the performance between scores at 3, 6 and 12 mo.RESULTS: The study population comprised 172 patients, of which 68.9% were male. The mean age of the patient was 47.5 ± 13 years. Hepatitis B virus infection was the cause of cirrhosis in 70% of the cases. The overall mortality was 31.4% over 11 years of follow up. Independent factors significantly associated with mortality were: CPT score (HR = 3.3, 95% CI [1.7-6.2]) (P < 0.001) (stage C vs stage A-B); Serum creatine (HR = 2.5, 95% CI [1.4-4.3]) (P = 0.001) (Serum creatine > 1.5 mg/dL versus serum creatine < 1.5 mg/dL); MELD score (HR = 2.9, 95% CI [1.63-5.21]) (P < 0.001) (MELD > 21 vs MELD < 21). The area under the curves (AUC) that predict survival was 0.72 and 0.75 at 3 mo (P = 0.68), 0.64 and 0.62 at 6 mo (P = 0.67), 0.69 and 0.64 at 12 mo (P = 0.38) respectively for the CPT score and the MELD score.CONCLUSION: The CPT score displays the sameprognostic significance as does the MELD score in black African patients with cirrhosis. Moreover, its handling appears less cumbersome in clinical practice as compared to the latter.

Symptom clusters and quality of life among patients with advanced heart failure

Objectives To identify symptom clusters among patients with advanced heart failure （HF） and the independent relationships with their quality of life （QoL）. Methods This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale （ESAS） and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hier- archical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities. Results The patients were at an advanced age （82.9± 6.5 years）. Three distinct symptom clusters were identified： they were the distress cluster （including shortness of breath, anxiety, and depression）, the decondition cluster （fatigue, drowsiness, nausea, and reduced appetite）, and the discomfort cluster （pain, and sense of generalized discomfort）. These three symptom clusters accounted for 63.25% of variance of the patients＇ symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress （β = -0.635, P 〈 0.001）, the decondition （β = -0.148, P = 0.01）, and the discomfort （β = -0.258, P 〈 0.001） symptom clusters independently predicted their QoL. Conclusions This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Role of the receptor for advanced glycation end products in hepatic fibrosis

AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.