Drug resistance mutation profiles of the drug-nave and first-line regimen-treated HIV-1-infected population of Suzhou, China

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance(TDR) and acquired drug resistance mutation(ADR) profiles, we collected blood specimens from 127 drug-naive and 117 first-line drugtreated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified po/fragments from 100 drug-naive and 20 drug-treated samples. We then determined the drugresistant mutations to protease(PR) and reverse-transcriptase(RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted(drug-naive group) and acquired(treated group) resistance mutations, respectively. Six transmitted drugresistant mutations were found, including two mutations(L33F and L76V) in the protease region and four(K70N/E and V179D/E) in the RT region. Only L76 V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Serum basic fibroblast growth factor and interleukin-1βpredict the effect of first-line chemotherapy in patients with advanced gastric cancer

BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma(aGC),it may lead to an adverse prognosis.Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients.AIM To determine the efficacy and safety of cetuximab(CET)combined with the FOLFOX4 regimen(infusional fluorouracil,folinic acid,and oxaliplatin)as firstline therapy for patients with aGC,who received evidence-based care(EBC).METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled.Of these,60 in the research group(RG)received CET+FOLFOX4 as first-line therapy,whereas 57 in the control group(CG)received FOLFOX4.The efficacy[clinical response rate(RR)and disease control rate(DCR)],safety(liver and kidney dysfunction,leukopenia,thrombocytopenia,rash,and diarrhea),serum tumor marker expression[STMs;carbohydrate antigen(CA)19-9,CA72-4,and carcinoembryonic antigen(CEA)],inflammatory indicators[interleukin(IL)-2 and IL-10],and quality of life(QOL)of the two groups were compared.RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG,with an equivalent safety profile between the two groups.RG exhibited notably reduced CA19-9,CA72-4,CEA,and IL-2 levels following treatment,which were lower than the pre-treatment levels and those in the CG.Post-treatment IL-10 was statistically increased in RG,higher than the pre-treatment level and the CG.Moreover,a significantly improved QOL was evident in the RG.CONCLUSION The CET+FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC.It facilitates the suppression of STMs,ameliorates the serum inflammatory microenvironment,and enhances QOL,without increased adverse drug effects.

Clinical Effects of the Follicular Phase Long Regimen and Luteal Phase Long Regimen on Ovulation Induction in IVF-ET Treatment: A Meta-Analysis

Objective:To systematically evaluate the clinical effects of the follicular phase long regimen and the luteal phase long regimen on ovulation induction in IVF-ET treatment.Methods:Databases including PubMed,Embase,Cochrane Library,CNKI,Chinese Biomedical Literature(CBM),VIP,Wanfang,and others were searched up to January 2021.Clinical studies on ovulation induction using the follicular phase long regimen and luteal phase long regimen in IVF-ET treatment were identified.Literature screening,data extraction,and quality evaluation were conducted based on inclusion and exclusion criteria.Meta-analysis was performed using RevMan 5.3 software.Results:After screening,a total of 11 studies were included,comprising 21,544 patients:9,974 in the follicular phase long regimen group and 11,570 in the luteal phase long regimen group.The meta-analysis results were as follows:(1)The number of Gn days and the total amount of Gn in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05);(2)The number of eggs obtained in the follicular phase long regimen was higher than that in the luteal phase long regimen(P<0.05).There were no significant differences in the rate of embryo optimization and cycle cancellation between the two groups(P>0.05);(3)The embryo implantation rate and clinical pregnancy rate in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05),while the abortion rate in the follicular phase long regimen was lower than that in the luteal phase long regimen(P<0.05).Conclusion:Compared to the luteal phase long regimen,the follicular phase long regimen involves more Gn days and a higher total amount of Gn.The optimal embryo rate and cycle cancellation rate were similar between the regimens,but the follicular phase long regimen resulted in more eggs,significantly improved the implantation and clinical pregnancy rates,and reduced the abortion rate.However,these conclusions require further validation through more multicenter,large-sample RCT studies.

Role of cetuximab in first-line treatment of metastatic colorectal cancer

The treatment of metastatic colorectal cancer(mCRC)has evolved considerably in the last decade,currently allowing most mCRC patients to live more than two years.Monoclonal antibodies targeting the epidermal growth factor receptor(EGFR)and vascular endothelial growth factor play an important role in the current treatment of these patients.However,only antibodies directed against EGFR have a predictive marker of response,which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS).Cetuximab has been shown to be effective in patients with KRAS wild-type mCRC.The CRYSTAL study showed that adding cetuximab to FOLFIRI(regimen of irinotecan,infusional fluorouracil and leucovorin)significantly improved results in the first-line treatment of KRAS wildtype mCRC.However,results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are contradictory.On the other hand,recent advances in the management of colorectal liver metastases have improved survival in these patients.Adding cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of patients.In this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication

AIM: To evaluate the efficacy of moxifloxacin-based sequential therapy(MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori(H. pylori) infection.METHODS: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST(MBST group, n = 140) or hybrid(Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated.RESULTS: The eradication rates in the intention-totreat(ITT) analysis were 91.4%(128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2%(114/144; 95%CI: 77.3%-80.7%) in the Hybrid group(P = 0.013). The eradication rates in the perprotocol(PP) analysis were 94.1%(128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6%(114/138; 95%CI: 80.6%-84.1%) in the Hybrid group(P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT(P = 0.013) and the PP analyses(P = 0.003). Both groups exhibited full compliance with treatment(MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8%(16/136) and 19.6%(27/138) in the MBST and Hybrid group, respectively(P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group.CONCLUSION: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.

Efficacy of moxifloxacin-based sequential therapy for first-line eradication of Helicobacter pylori infection in gastrointestinal disease

AIM:To evaluate the efficacy of 14-d moxifloxacinbased sequential therapy as first-line eradication treatment of Helicobacter pylori(H.pylori) infection.METHODS:From December 2013 to August 2014, 161 patients with confirmed H.pylori infection randomly received 14 d of moxifloxacin-based sequential group(MOX-ST group, n = 80) or clarithromycin-based sequential group(CLA-ST group, n = 81) therapy.H.pylori infection was defined on the basis of at least one of the following three tests:a positive 13C-urea breath test; histologic evidence of H.pylori by modified Giemsa staining; or a positive rapid urease test(CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test four weeks after the end of eradication treatment.Compliance was defined as good when drug intake was at least 85%.H.pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.RESULTS:The eradication rates by intention-to-treat analysis were 91.3%(73/80;95%CI:86.2%-95.4%)in the MOX-ST group and 71.6%(58/81;95%CI:65.8%-77.4%)in the CLA-ST group(P=0.014).The eradication rates by per-protocol analysis were 93.6%(73/78;95%CI:89.1%-98.1%)in the MOX-ST group and 75.3%(58/77;95%CI:69.4%-81.8%)in the CLAST group(P=0.022).Compliance was 100%in both groups.The adverse event rates were 12.8%(10/78)and 24.6%(19/77)in the MOX-ST and CLA-ST group,respectively(P=0.038).Most of the adverse events were mild-to-moderate in intensity;there was none serious enough to cause discontinuation of treatmentin either group.In multivariate analysis,advanced age(≥60 years)was a significant independent factor related to the eradication failure in the CLA-ST group(adjusted OR=2.13,95%CI:1.97-2.29,P=0.004),whereas there was no significance in the MOX-ST group.CONCLUSION:The 14-d moxifloxacin-based sequential therapy is effective.Moreover,it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication:A randomized study in Japan

AIM:To find the way to improve the eradication rate of first-line therapy in Japanese patients.METHODS:We prospectively compared the effectiveness of 7-d quadruple therapy to standard 7 d triple therapy in Japanese patients infected with Helicobacter pylori(H.pylori).One hundred and nineteen patients were randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,amoxicillin,clarithromycin and metronidazole(LACM7) or 7-d triple therapy with lansoprazole,amoxicillin and clarithromycin(LAC7).After three months,H.pylori status was analyzed by 13C-urea breath test.Incidence rates of adverse events were evaluated by use of questionnaires.RESULTS:By intention-to-treat(ITT) analysis,the eradication rate in the LACM7 group was 94.9%,which was significantly higher than the LAC7 group(68.3%,P < 0.001).Per protocol analysis also showed a significantly higher eradication rate in the LACM7 group(98.3%) than the LAC7 group(73.2%,P < 0.001).Nevertheless,the incidence of serious adverse events did not differ between the two groups(RR:1.10,95% CI:0.70-1.73,P = 0.67).CONCLUSION:Seven day non-bismuth quadruple therapy(LACM7) was superior to standard 7-d triple therapy(LAC7) for first-line eradication.

First-line cisplatin,docetaxel,and cetuximab for patients with recurrent or metastatic head and neck cancer:A multicenter cohort study

BACKGROUND The targeted therapy cetuximab[directed at the epidermal growth factor receptor(EGFR)]in combination with 5-fluorouracil and platinum-based chemotherapy(the EXTREME regimen)has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck(R/M SCCHN).Thus,this scheme has been established as the preferred first-line option for these patients.However,more recently,a new strategy combining platinum,taxanes,and cetuximab(the TPEx regimen)has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials.AIM To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study.METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1,2017 and April 31,2020.Chemotherapy consisted of four cycles of docetaxel,cisplatin,and cetuximab followed by cetuximab maintenance therapy.Clinical outcomes and toxicity profiles were collected from medical charts.Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors(version 1.1).Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 4.0).RESULTS Twenty-four patients were included.The median age at diagnosis was 58 years(range:36-77 years).The majority of patients(83.3%)received at least four chemotherapy cycles in the initial phase.In the included group,the overall response rate was 62.5%,and 3 patients achieved a complete response(12.5%).The median time to response was 2.4 mo[95% confidence interval(CI):1.3-3.5].With a median follow-up of 12.7 mo(95%CI:8.8-16.6),the median progression-free survival(PFS)was 6.9 mo(95%CI:6.5-7.3),and the overall survival rate at 12 mo was 82.4%.Patients with documented tumor response showed a better PFS than those with disease stabilization or progression[8.5 mo(95%CI:5.5-11.5)and 4.5 mo(95%CI:2.5-6.6),respectively;P=0.042].Regarding the safety analysis,two-thirds of patients reported at least one treatment-related adverse event,and 25% presented grade 3 toxicities.Of note,no patient experienced grade 4 adverse events.CONCLUSION TPEx was an adequately tolerated regimen in our population,with low incidence of grade 3-4 adverse events.The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination.This regimen may be considered an attractive therapeutic strategy due to its simplified administration,decreased total number of chemotherapy cycles,and treatment tolerability.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer

Objective： To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods： Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results： None of the patients achieved a complete response （CR）, while 15 patients achieved a partial remission （PR） and 17 experienced a stable disease （SD）. Thirteen patients continued to have a progressive disease （PD）. The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash （53.3%） and diarrhea （33.3%）. Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion： Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Paclitaxel-etoposide-carboplatin/cisplatin versus etoposidecarboplatin/cisplatin as first-line treatment for combined small-cell lung cancer: a retrospective analysis of 62 cases

Objective: To compare the efficacy and adverse effects of paclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE) regimen with those of etoposide-carboplatin/cisplatin(EP/CE) regimen as first-line treatment for combined small-cell lung cancer(CSCLC).Methods: A retrospective study was conducted on 62 CSCLC patients who were treated at Tianjin Medical University Cancer Institute and Hospital from July 2000 to April 2013 and administered with TEP/TCE regimen(n=19) or EP/CE regimen(n=43) as first-line CSCLC treatment. All patients received more than two cycles of chemotherapy, and the response was evaluated every two cycles. The primary endpoint was overall survival(OS), and the secondary endpoints were progression-free survival(PFS), objective response rate(ORR), disease control rate(DCR), and adverse effects. Results: ORR between the TEP/TCE and EP/CE groups showed a statistical difference(90% vs. 53%, P=0.033). Both groups failed to reach a statistical difference in DCR(100% vs. 86%, P=0.212). The median PFS and OS of the TEP/TCE group were slightly longer than those of the EP/CE group, although both groups failed to reach a statistical difference(10.5 vs. 8.9 months, P=0.484; 24.0 vs. 17.5 months, P=0.457). However, stratified analysis indicated that the PFS of patients with stages III and IV CSCLC showed marginally significant difference between the TEP/TCE and EP/CE groups(19.5 vs. 7.6 months; P=0.071). Both rates of grade IV bone marrow depression and termination of chemotherapy in the TEP/TCE group were significantly higher than those in the EP/CE group(26.3% vs. 7.0%, P=0.036; 31.6% vs. 14.7%, P=0.004). Conclusion: The TEP/TCE regimen may not be preferred for CSCLC, and this three-drug regimen requires further exploration and research. To date, the EP/CE regimen remains the standard treatment for CSCLC patients.

Adjusting phosphate feeding regimen according to daily rhythm increases eggshell quality via enhancing medullary bone remodeling in laying hens

Background Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle.The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms.There is lack of information about the impact of adjusting phosphate feeding regimen according to daily rhythm on the phosphorus homeostasis and bone remodeling of laying hens.Methods and results Two experiments were conducted.In Exp.1,Hy-Line Brown laying hens(n=45)were sampled according the oviposition cycle(at 0,6,12,and 18 h post-oviposition,and at the next oviposition,respectively;n=9 at each time point).Diurnal rhythms of body calcium/phosphorus ingestions and excretions,serum calcium/phosphorus levels,oviduct uterus calcium transporter expressions,and medullary bone(MB)remodeling were illustrated.In Exp.2,two diets with different phosphorus levels(0.32%and 0.14%non-phytate phosphorus(NPP),respectively)were alternately presented to the laying hens.Briefly,four phosphorus feeding regimens in total(each included 6 replicates of 5 hens):(1)fed 0.32%NPP at both 09:00 and 17:00;(2)fed 0.32%NPP at 09:00 and 0.14%NPP at 17:00;(3)fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00;(4)fed 0.14%NPP at both 09:00 and 17:00.As a result,the regimen fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00,which was designed to strengthen intrinsic phosphate circadian rhythms according to the findings in Exp.1,enhanced(P<0.05)MB remodeling(indicated by histological images,serum markers and bone mineralization gene expressions),elevated(P<0.05)oviduct uterus calcium transportation(indicated by transient receptor potential vanilloid 6 protein expression),and subsequently increased(P<0.05)eggshell thickness,eggshell strength,egg specific gravity and eggshell index in laying hens.Conclusions These results underscore the importance of manipulating the sequence of daily phosphorus ingestion,instead of simply controlling dietary phosphate concentrations,in modifying the bone remodeling process.Body phosphorus rhythms will need to be maintained during the daily eggshell calcification cycle.

Comparative effectiveness of first-line therapies for eradication of antibiotic-resistant Helicobacter pylori strains:A network metaanalysis

BACKGROUND As a first-line treatment regimen for Helicobacter pylori(H.pylori)infection,antibiotic therapy is widely used worldwide.However,the question of increasing antibiotic resistance must be considered.Given this issue,we need to find ways to reduce drug resistance.This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials(RCTs).AIM To compare first-line treatment regimens for eradication of antibiotic-resistant H.pylori strains.METHODS To compare the effectiveness of the first-line regimens for treating H.pylori infection,a Bayesian network meta-analysis was applied to process data extracted from RCTs.The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve(SUCRA).In addition,we conducted a relevant search by reference citation analysis.RESULTS Twenty-five RCTs involving 12029 participants[including 1602 infected with clarithromycin(CAM)-resistant strains and 1716 infected with metronidazole(MNZ)-resistant strains]were included,in which a total of seven regimens were used for H.pylori eradication.The results showed that dual therapy containing a high-dose proton pump inhibitor(HDDT)[odds ratio(OR):4.20,95%confidence interval(CI):2.29-8.13]was superior to other therapies for all patients,including those with CAM/MNZ-resistant H.pylori infection.In the comparative effectiveness ranking,for CAM-resistant H.pylori,HDDT(OR:96.80,95%CI:22.46-521.9)had the best results,whereas standard triple therapy ranked last(SUCRA:98.7%vs 0.3%).In the subgroup of high cure rates(≥90%),HDDT was also generally better than other therapies.CONCLUSION For the eradication of CAM-and MNZ-resistant H.pylori strains,HDDT exhibited considerable advantages.The studies of CAM-resistant H.pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs,but the results showed that all patients,including those with CAM-resistant H.pylori infection,had a concordant trend.Overall,HDDT may be a reference for RCTs and other studies of H.pylori eradication.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.