Synthesis of 4-Arylpolyhydroquinoline Derivatives and Evaluation of Their Antitumor Activities

Four novel 4-arylpolyhydroquinoline derivatives（1~4） were synthesized and characterized via IR,~1H NMR,H RMS,and single-crystal X-ray crystallography. It crystallizes in triclinic,space group P1 with a = 7.382（5）,b = 10.766（7）,c = 11.583（8） ？,α = 66.077（10）,β = 77.461（10）,γ = 82.590（11）o,V = 820.6（10） ？~3,Z = 2,F（000） = 332,Dc = 1.260 Mg/m^3,Mr = 311.37 and μ = 0.085 mm-1. In addition,the antitumor effects of compounds 1~4 were studied on three human tumor cells（NCI-H1688,AGS and 95-D）. The results showed that compared with compounds 1 and 2,compounds 3 and 4 displayed efficient antitumor activity.

Enhancing competency of clinical research nurses:A comprehensive training and evaluation framework

The Sun et al's training program for clinical research nurses(CRNs)in the World Journal of Clinical Cases is a comprehensive and scientific approach.It includes structured frameworks for CRN training,aiming to improve CRN competency.This program emphasizes practical abilities,updates training content,and improves evaluation methods.The cultivation of CRN talents focuses on enhancing the training system,establishing a multifaceted evaluation framework,and continuously refining the training programs.Regular feedback and evalua-tion are essential to improve CRNs'competency in practical settings.

Effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role

Objective:To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cell HT29 xenograft of nude mice model was established.The expression of ECF,VEGF,gastric cancer tumor growth in mice were observed.Results:Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group(P<0.05).Conclusions:Tumor can inhibit the expression of PKC inhibition.Yiqi Jianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.

Surveillance colonoscopy practice in Lynch syndrome in the Netherlands:A nationwide survey

Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common genetic disorder predisposing to colorectal cancer. As regular colonoscopic surveillance has been shown to reduce the incidence of colorectal cancer, this strategy is recommended worldwide. Recently, several advances in colonoscopic techniques have improved detection rates of neoplasia in Lynch syndrome. In this nationwide survey, we evaluated current surveillance colonoscopy practices for Lynch syndrome in the Netherlands and the extent to which advanced techniques have been adopted in routine clinical practice.

Thermal ablation and immunotherapy for hepatocellular carcinoma:Recent advances and future directions

Hepatocellular carcinoma(HCC)is one of most common cancers that cause death in the world.Thermal ablation(TA)is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation.Particularly for small and early HCCs,TA can be considered as the first-line curative treatment.However,local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly.Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients,which has the potential to reduce the tumor recurrence and metastasis.The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence.Herein we summarize the latest progress in TA,immunotherapy,and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45

AIM：To clarify the role of activated Notch2 in the invasiveness of gastric cancer.METHODS：To investigate the invasiveness of silencing Notch2 gene expression,we established a Notch2small interfering RNA（siRNA） transfected cell line using the MKN-45 gastric cancer cell line.After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction（RT-PCR） and Western blotting,migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer.RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9（MMP9）,Akt,p-Akt.To confirm the relationship between PI3KAkt and MMP9,the PI3K inhibitor LY294002 was used to treat MKN-45 cells.RESULTS：Notch2 expression was dramatically decreased after Notch2 siRNA transfection（100.00% ± 9.74% vs 11.61% ± 3.85%,P 〈 0.01 by qRT-PCR）.There was also a marked reduction of Notch target gene Hes1（100.00% ± 4.74% vs 61.61% ± 3.58%,P 〈 0.05） at the mRNA,indicating an inhibition of Notch signaling.Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels（100.00% ± 9.74% vs 65.61% ± 7.58%,P 〈 0.05）.Down-regulation of Notch2 by siRNA enhanced tumor cell invasion（100.00% ± 21.64% vs 162.22% ± 16.84%,P 〈 0.05） and expression of MMP9（1.56 fold,P 〈 0.05）,and activated the pro-MMP9 protein to its active form（1.48 fold,P 〈 0.05）.There was no significant difference in the protein levels of Akt between the two groups（100.00% ± 10.87% vs 96.61% ± 7.33%,P 〉 0.05）,while down-regulation of Notch2 elevated p-Akt expression（100.00% ± 9.87% vs 154.61% ± 13.10%,P 〈 0.05）.Furthermore,p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002（p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%,P 〈 0.05;MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%,P 〈 0.05）.CONCLUSION：Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling pathway

United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment

AIM: To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. METHODS: United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. Resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. Resource categories used in the analysis include: Treatments (e.g. , surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). RESULTS: Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of these technologies compared to pNET. Chemotherapy utilization was also greater among GI/Lung types. Multivariate analysis results demonstrated that patients in first progression period were over 3 times more likely to receive chemotherapy when compared to baseline (odds ratio: 3.31; 95%CI: 1.46-7.48, P=0.0041). Further, progression was associated with a greater likelihood of having a study physician visit [relative risk (RR): 1.54; 95%CI: 1.10-2.17, P=0.0117], and an increased frequency of other physician visits (RR: 1.84; 95%CI: 1.10-3.10, P=0.0211). CONCLUSION: Resource utilization in advanced NET in the United States is significant overall and data suggests progression has an impact on resource utilization regardless of NET tumor site.

High burden of hepatocellular carcinoma and viral hepatitis in Southern and Central Vietnam:Experience of a large tertiary referral center,2010 to 2016

AIM To examine the largest tertiary referral center in southern and central Vietnam from 2010 to 2016, evaluating epidemiological trends of hepatocellular carcinoma(HCC) and viral hepatitis B-C in this resource-limited setting.METHODS We extracted data of patients receiving care from Cho Ray Hospital(Ho Chi Minh City), the largest oncology referral center in southern and central Vietnam, from 2010 to 2016. We collected information on patient age, gender, geographic distribution, and disease characteristics including disease stage, tumor biomarker levels [serum alpha-fetoprotein(AFP), AFP-L3 isoform percentage, and prothrombin induced by induced by vitamin K absence-Ⅱ], and serological testing for hepatitis B virus(HBV) and hepatitis C virus(HCV) infections.RESULTS Data from 24091 HCC patients were extracted, with sample demographics comprising mostly male(81.8%) and older age(however with 8.5% younger than 40 years old). This patient sample included a geographic catchment population of 56 million people(60% of the country's total population of 92.7 million), derived from 38 provinces and municipalities in Vietnam. Chronic HBV infection was found in 62.3% of cases, and chronic HCV infection in 26.0%. HBV and HCV co-infection was seen in 2.7%. Cirrhosis was found in an estimated 30% to 40% of cases. Nine percent of patients were not found to have chronic viral hepatitis. Twenty three point two percent of the patients had a normal AFP level. A total of 2199 patients were tested with AFP-L3 and PIVKA Ⅱ over two years, with 57.7% having elevated AFP-L3%, and 88.5% with elevated PIVKA Ⅱ levels. Over this 7-year period, the incidence of HCC increased, with a large proportion of cases(overall 40.8%) presenting initially an advanced stage, not amendable to surgical or locoregional therapy.CONCLUSION HCC contributes significant health care burden in southern and central Vietnam, with increasing case volume over this seven-year period. Viral hepatitis likely explains this high HCC prevalence.

C19MC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.

Potential role of human papilloma virus in the pathogenesis of gastric cancer

AIM: To demonstrate the presence and biological activity of human papilloma virus (HPV) in gastric cancer (GAC) tissues.

Clinical Effects of Lianbai Liquid in Prevention and Treatment of Dermal Injury Caused by Radiotherapy

Objective: To observe the effect of Lianbai liquid (连柏液) in prevention and treatment of acute radiation dermal injury. Method: From May 2000 to December 2005, 126 cancer patients were randomly divided into a prevention group of 75 cases given externally topical application of Lianbai liquid since the first radiotherapy, and a control group Ⅰ of 51 cases given only advice after radiotherapy; while the other 92 cancer patients who had already had grade Ⅲ acute radiation-induced dermal injury were randomly divided into a treatment group of 54 cases treated by externally topical use of Lianbai liquid, and a control group Ⅱ of 38 cases treated by topical use of norfloxacin. Clinical evaluation was carried out according to the CTC.V2.0 standard stipulated by NCI for classifying acute radiation dermal injury. Results: The incidence of skin reaction was 32.0% in the prevention group and 92.2% in the control group Ⅰ, with an obvious difference between the two groups (χ2=54.163, P<0.01). Mild radioactive reaction (grade Ⅰ and Ⅱ) was 28.0% (21/75) in the prevention group and 70.6% (36/51) in the control group Ⅰ, with a remarkable difference between the two groups (χ2=22.226, P<0.01). The effective rate for grade Ⅲ dermal injury was 92.6% (50/54) in the treatment group and 65.9% (25/38) in the control group Ⅱ, with a remarkable difference between the two groups (χ2=6.018, P=0.024). The wound-healing time was 11.07±2.21 days in the treatment group and 18.08±1.76 days in the control group Ⅱ, with a remarkable difference between the two groups (u=16.932, P<0.01). Conclusion: Lianbai liquid can effectively prevent the radiation dermatitis, and treat grade Ⅲ acute radiation dermal injury with obvious curative effect.

Single-Exosome Profiling Identifies ITGB3+and ITGAM+Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer

Tumor metastasis is a hallmark of colorectal cancer(CRC),in which exosome plays a crucial role with its function in intercellular communication.Plasma exosomes were collected from healthy control(HC)donors,localized primary CRC and liver-metastatic CRC patients.We performed proximity barcoding assay(PBA)for single-exosome analysis,which enabled us to identify the alteration in exosome subpopulations associated with CRC progression.By in vitro and in vivo experiments,the biological impact of these subpopulations on cancer proliferation,migration,invasion,and metastasis was investigated.The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA.Twelve distinct exosome subpopulations were determined.We found 2 distinctly abundant subpopulations:one ITGB3-positive and the other ITGAM-positive.The ITGB3-positive cluster is rich in liver-metastatic CRC,compared to both HC group and primary CRC group.On the contrary,ITGAM-positive exosomes show a large-scale increase in plasma of HC group,compared to both primary CRC and metastatic CRC groups.Notably,both discovery cohort and validation cohort verified ITGB3+exosomes as potential diagnostic biomarker.ITGB3+exosomes promote proliferation,migration,and invasion capability of CRC.In contrast,ITGAM+exosomes suppress CRC development.Moreover,we also provide evidence that one of the sources of ITGAM+exosomes is macrophage.ITGB3+exosomes and ITGAM+exosomes are proven 2 potential diagnostic,prognostic,and therapeutic biomarkers for management of CRC.

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia

AIM： To determine DNA aneuploidy in mucosal biopsies of achalasia patients for subsequent rapid diagnosis. METHODS： Biopsies from the middle third of the esophagus were obtained in 15 patients with achalasia. Immunohistochemical staining was carried out with monoclonal antibodies MIB-1 for Ki67 and PAb 1801 for p53, in addition to the conventional histologic examination for dysplasia. Nuclei of fresh biopsy material were enzymatically and mechanically isolated, and the DNA content was determined with image cytometry after Feulgen staining. DNA grading of malignancy was assessed according to Boecking to determine the variability of DNA values noted around the normal diploid peak. Further indices measured included the aneuploid rate, and the 5c-, 7c- and 9c-exceeding rate. RESULTS： The histological examination did not demonstrate dysplasia; while MIB-1 （basal） showed a positive reaction in 8/15 achalasia specimens, p53 was negative in all specimens. Image cytometric DNA analysis detected aneuploidy in 4/15 （26.7%） specimens. Samples from 15 patients with squamous cell carcinoma as well as specimens obtained exclusively 2 cm proximal to the tumor served as reference tests. All carcinomas （15/15） as well as 9 of the peritumoral samples （9/15） were aneuploid. The comparison of biopsies from achalasia patients with peritumoral and carcinoma specimens revealed statistically significant differences regarding the aneuploid rate （diploid： P 〈 0.0001; tetraploid： P = 0.001）, grading of malignancy according to Boecking （P 〈 0.0001） and the 5c- （P 〈 0.0001）, 7c-（P 〈 0.0001）, and 9c- （P = 0.0001） exceeding rate with progredient DNA alterations in the respective order. CONCLUSION： The finding that DNA aneuploidy was identified by image cytometry in esophageal specimens of patients with achalasia, which may be due to specific chromosomal alterations presenting as precancerous lesions in 27% of patients, leads us to conclude that image cytometry represents a valuable screening tool.

Recent advances of multimoda ultrasound in image-guided prostate-targeted biopsy

Prostate-targeted biopsy is usually the preferred method over systematic biopsy because it can effectively detect prostate cancer using only a few puncture cores with fewer complications.With the development of ultrasound,it has gained multimodal technological upgrades,such as the emergence of contrast-enhanced ultrasound,ultrasound elastography,and three-dimensional ultrasonography.Moreover,multimodal ultrasound has played an increasingly significant role in prostate-targeted biopsies.

The Impact of Joint Replacement on Driver Function and Safety

Background: The timing of return-to-driving following total joint replacement has not been well-defined. The primary aim is to study the impact of joint replacement on driver safety. A secondary aim is to investigate the possible predictors for increased car accidents in patients undergoing total joint replacement surgery. This data will provide the background to support further prospective studies on the relationship of driver safety to joint replacement surgery. Methods: A retrospective analysis of driver safety in the postoperative period was performed by analyzing the self-reporting of 485 patients who had undergone a Total Hip Arthroplasty (n = 196), Total Knee Arthroplasty (n = 258) or Total Shoulder Arthroplasty (n = 31). The mean age was 70 (28 - 88) with 164 male (34%) and 319 female (66%). Patients were mailed a questionnaire and the responses were analyzed to determine what factors affect driving after joint replacement. Results: Overall, increased patient age and gender were associated with increased accidents following surgery. Our subgroup analysis demonstrated that in patients undergoing TSA, increased patient age was associated with increased accidents. TKA patients showed that older patient age predicted increased accidents following surgery. Conclusions: While age and gender are correlated with increased accidents after joint replacement in general, no factors specific to joint replacement surgery are related to increased incidence of accidents.

Clinical Observation on the Combined Treatment of 57 Cases of Non-small Cell Lung Cancer Using Argon-Helium Cryosurgery and Chinese Herbal Medicine

Objective： To observe the clinical effect of the combined therapy using argon-helium cryosurgery （Ar-He knife） and Chinese herbal medicine in treating non-small cell lung cancer （NSCLC）. Methods： Fifty-seven patients of NSCLC were treated with the combined therapy and observed. Results： The treatment was successfully completed in all patients with mild adverse reactions. The effective rate was 83.8% 3 months after the operation, 79.6% 6 months after the operation, and 77.3% 12 months after the operation, with median survival of 9 months. The survival rate after 12 months was 46.67% （21/45）, 34.62% （9/26） after 18 months, and 36.36% （4/11） after 24 months. Conclusion： Argon-helium cryosurgery therapy is superior in its assured orientation, quick tumor load deprivation and less post- operational reaction. Combined with Chinese herbal medication, Argon-helium cryosurgery therapy can prolong survival time, relieve clinical symptoms, and elevate the quality of life in NSCLC patients, and is thus worthy of promotion.

A mesenchymal-like subpopulation in non-neuroendocrine SCLC contributes to metastasis

Small cell lung cancer(SCLC)is the most aggressive lung cancer with high heterogeneity.Mouse SCLC cells derived from the Rb1L/L/Trp53L/L(RP)autochthonous mouse model grew as adhesion or suspension in cell culture,and the adhesion cells are defined as non-neuroendocrine(non-NE)SCLC cells.Here,we uncover the heterogenous subpopulations within the non-NE cells and referred to them as mesenchymallike(Mes)and epithelial-like(Epi)SCLC cells.The Mes cells have increased capability to form colonies in soft agar and harbored stronger metastatic capability in vivo when compared with the Epi cells.Gene Set Enrichment Analysis reveals that the transforming growth factor(TGF)-βsignaling is enriched in the Mes cells.Importantly,inhibition of the TGF-βsignaling through ectopic expression of dominant-negative Tgfbr2(Tgfbr2-DN)or treatment with Tgfbr1 inhibitor SD-208 consistently abrogates tumor metastasis in nude mouse allograft assays.Moreover,genetic deletion of Tgfbr2 or Smad4,the key components of the TGF-βsignaling pathway,dramatically attenuates SCLC metastasis in the RP autochthonous mouse model.Collectively,our results uncover the high heterogeneity in non-NE SCLC cells and highlight an important role of TGF-βsignaling in promoting SCLC metastasis.

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.

Therapeutic Mechanisms of Single Chinese Medicine Herb or Their Extracts for Extrahepatic Obstructive Jaundice

Obstructive jaundice （O J） is classified as extrahepatic OJ or intrahepatic OJ. Extrahepatic OJ is attributed to a variety of intricate etiological factors. Research has begun with Chinese medicine （CM）, which can be used as an adjunctive therapy for extrahepatic OJ. Particular attention has been paid to the therapeutic effects and their mechanisms of single CM herb and relevant extracts. The roles of single CM or their extracts during adjunctive therapy for extrahepatic OJ have been described briefly, This review focuses on the effects and their mechanisms of relevant herbal medicines.