Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019

BACKGROUND Gallbladder and biliary diseases(GABDs)are a major public health issue.AIM To analysis the cause-specific incidence,prevalence,and years lived with disability(YLDs)and its temporal trends of GABDs at the global,regional,and national level.Data on GABD were available from the Global Burden of Disease study 2019.METHODS The estimated annual percentage change(EAPC)was used to quantify temporal trend in GABD age-standardized incidence rates(ASIRs),age-standardized prevalence rate(ASPR),and age-standardized YLD rate(ASYR)by region,sex.We analyzed the relationship between the GABD burden and country development level using the human development index(HDI).RESULTS In 2019,the incident cases of GABD were 52003772,with an ASIR of 63432/100000 population.Globally,the number of incident cases and ASIR of GABD increased 97%and 58.9%between 1990 and 2019.Although,the ASPR and ASYR decreased from 1990 to 2019,the number of prevalent and YLDs cases increased.The highest ASIR was observed in Italy,and the highest ASPR and ASYR was observed in United Kingdom.The highest burden of GABD was found in low-SDI region,and the burden in female was significantly higher than males.A generally negative correlation(ρ=-0.24,P<0.05)of GABD with the EAPC and human development index(HDI)(in 2021)were observed for ASIR.What’s more,no correlation in ASPR(ρ=-0.06,P=0.39)and ASYR(ρ=-0.07,P=0.36)of GABD with the EAPC and HDI(in 2021)were observed,respectively.CONCLUSION GABD remain a major global public health challenge;however,the burden of GABD varies geographically.Globally,the number of incident cases and ASIR of GABD increased between 1990 and 2019.The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.

Efficacy of the WINROP algorithm for retinopathy of prematurity screening in Southern China

AIM:To evaluate the predicting efficacy of severe retinopathy of prematurity(ROP)by the WINROP algorithm(http://winrop.com)in Southern China.METHODS:All preterm infants with the gestational age(GA)less than 32 wk were included.Their ROP screening results and serial postnatal body weight were analysed retrospectively.Weekly body weight was entered into and measured by the WINROP system.The outcomes were analysed,and the sensitivity,specificity,positive predictive value and negative predictive value(NPV)were calculated.RESULTS:Totally 432 infants with a median GA of 30.0(24.0-31.9)wk,and a median birth weight(BW)of 1360(540-2700)g were included.Among these 432 infants,50 were diagnosed as type 1 ROP but only 28 were identified by the WINROP algorithm.The sensitivity was 56%(28/50)and the NPV was 92%(252/274).However,for infants with BW<1000g or GA<28 wk,the sensitivity was 93.8%(15/16)and 93.3%(14/15),respectively.Meanwhile,with several postnatal complications added as additional risk factors,the sensitivity was increased to 96%(48/50).CONCLUSION:The sensitivity of the WINROP algorithm from the Southern Chinese cohort is not as high as that reported in developed countries.This algorithm is effective for detecting severe ROP from extremely small or preterm infants.Modification of the algorithm with additional risk factors could improve the predictive value for infants with a GA>28 wk in China.

Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling

BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.

96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients

Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatment.Here,we update 96-week comparison results.Methods:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks.The virological suppression was defined as HBV DNA levels<20 IU/mL at week 96.Safety was evaluated thoroughly with focusing on bone,renal,and metabolic pa-rameters.Results:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations.Noninferior efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at baseline.Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving TDF.In addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.Conclusions:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.

Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial

WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.

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.

不同力度推桥弓治疗Ⅰ级原发性高血压的疗效观察

目的:观察不同力度推桥弓治疗Ⅰ级原发性高血压的临床疗效.方法:将72例Ⅰ级原发性高血压患者采用随机数字表法分为对照组、轻推桥弓组和重推桥弓组,每组24例.三组均接受相同的治疗性生活方式干预.对照组不接受其他干预;轻推桥弓组加用轻手法推桥弓穴治疗;重推桥弓组加用重手法推桥弓穴治疗.治疗4周,随访4周,观察分析三组治疗后及随访时血压变化情况.结果:治疗后,三组患者的血压水平均有降低(P<0.05).对照组有效率43.5%;轻推桥弓组有效率78.3%;重推桥弓组有效率33.3%.轻推桥弓组患者血压降低水平显著优于对照组和重推桥弓组,组间差异均具有统计学意义(P<0.01);重推桥弓组与对照组疗效相当,差异无统计学意义(P>0.05).随访时,与同组治疗结束时比较,对照组及轻推桥弓组的血压水平表现稳定,组内差异均无统计学意义(P>0.05);重推桥弓组的舒张压(DBP)及平均血压(MBP)均较治疗结束时降低,组内差异均具有统计学意义(P<0.05).随访时,轻推桥弓组收缩压(SBP)及MBP均低于重推桥弓组及对照组,组间差异均具有统计学意义(P<0.01),而DBP差异无统计学意义(P>0.05);重推桥弓组的SBP、DBP及MBP与对照组差异均无统计学意义(P>0.05).结论:轻手法推桥弓配合生活方式干预治疗Ⅰ级原发性高血压有效率高,远期血压平稳;不同力度推桥弓对Ⅰ级原发性高血压患者的影响存在差异.