Efficacy and safety of perioperative therapy for locally resectable gastric cancer:A network meta-analysis of randomized clinical trials

BACKGROUND Gastric cancer(GC)is the fifth most commonly diagnosed malignancy worldwide,with over 1 million new cases per year,and the third leading cause of cancer-related death.AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC.METHODS A comprehensive literature search was conducted,focusing on phase II/III randomized controlled trials(RCTs)assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC.The R0 resection rate,overall survival(OS),disease-free survival(DFS),and incidence of grade 3 or higher nonsurgical severe adverse events(SAEs)associated with various perioperative regimens were analyzed.A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.RESULTS Thirty RCTs involving 8346 patients were included in this study.Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone,and the former had the highest probability of being the most effective option in this context.Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS.Owing to limited data,no definitive ranking could be determined for DFS.Considering nonsurgical SAEs,FLO has emerged as the safest treatment regimen.CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC.Further studies are required to validate these findings.

Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety

BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of patients[5,6].Therefore,timely and effective therapeutic inter-ventions are of great significance for improving patient prognosis and ensuring therapeutic effects.Somatostatin(SS),a peptide hormone that can be secreted by endocrine cells and the central nervous system,is in-volved in the regulatory mechanism of glucagon and insulin synthesis in the pancreas[7].It has complex and pleiotropic effects on the gastrointestinal tract,which can inhibit the release of gastrointestinal hormones and negatively modulate the exocrine function of the stomach,pancreas and bile,while exerting a certain influence on the absorption of the di-gestive system[8,9].SS has shown certain clinical effectiveness when applied to SAP patients and can regulate the severity of SAP and immune inflammatory responses,and this regulation is related to its influence on leukocyte apoptosis and adhesion[10,11].Computerized tomography-guided therapeutic percutaneous puncture catheter drainage(CT-TPPCD)is a surgical procedure to collect lesion fluid and pus samples from necrotic lesions and perform puncture and drainage by means of CT image examination and precise positioning[12].In the research of Liu et al[13],CT-TPPCD applied to pa-tients undergoing pancreatic surgery contributes to not only good curative effects but also a low surgical risk.Baudin et al[14]also reported that CT-TPPCD has a clinical success rate of 64.6%in patients with acute infectious necrotizing pan-creatitis,with nonfatal surgery-related complications found in only two cases,suggesting that this procedure is clinically effective and safe in the treatment of the disease.In light of the limited studies on the efficacy and safety of SS plus CT-TPPCD in SAP treatment,this study performed a relevant analysis to improve clinical outcomes in SAP patients.

Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

Objective： To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 （HER2）-overexpressing advanced breast cancer. Methods： A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3（＋） staining in immunochemistry or amplification of fluorescence in situ hybridization （FISH, ratio ≥2.0）. Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival （PFS） and overall survival （OS）. Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox＇s proportional hazards regression model, and the level of significance was P〈0.05. Results： All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 （80.00%） patients had visceral metastasis, and 43 （47.78%） patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months （range, 2-59 months）, and the median OS after metastasis or initially local advanced disease was 22 months （range, 2-1 16 months）. Conclusions： Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.

Comparison of safety,efficacy,and long-term follow-up between“one-step”and“step-up”approaches for infected pancreatic necrosis

BACKGROUND Although the“Step-up”strategy is the primary surgical treatment for infected pancreatic necrosis,it is not suitable for all such patients.The“One-step”strategy represents a novel treatment,but the safety,efficacy,and long-term follow-up have not yet been compared between these two approaches.AIM To compare the safety,efficacy,and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment.METHODS This was a retrospective analysis of infectious pancreatic necrosis patients who underwent“One-step”or“Step-up”necrosectomy at Xuan Wu Hospital,Capital Medical University,from May 2014 to December 2020.The primary outcome was the composite endpoint of severe complications or death.Patients were followed up every 6 mo after discharge until death or June 30,2021.Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0,and statistical significance was set at P<0.05.RESULTS One-hundred-and-fifty-eight patients were enrolled,of whom 61 patients underwent“One-step”necrosectomy and 97 patients underwent“Step-up”necrosectomy.During the long-term follow-up period,40 patients in the“Onestep”group and 63 patients in the“Step-up”group survived.The time from disease onset to hospital admission(53.69±38.14 vs 32.20±20.75,P<0.001)and to initial surgical treatment was longer in the“Step-up”than in the“One-step”group(54.38±10.46 vs 76.58±17.03,P<0.001).Patients who underwent“Step up”necrosectomy had a longer hospitalization duration(65.41±28.14 vs 52.76±24.71,P=0.02),and more interventions(4.26±1.71 vs 3.18±1.39,P<0.001).Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group.Although the incisional hernia incidence was higher in the“One-step”group,no significant difference was found in the composite outcomes of severe complications or death,new-onset organ failure,postoperative complications,inflammatory indicators,long-term complications,quality of life,and medical costs between the groups(P>0.05).CONCLUSION Compared with the“Step-up”approach,the“One-step”approach is a safe and effective treatment method with better long-term quality of life and prognosis.It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.

Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

To the Editor:Biliary drainage is most frequently performed among endoscopic procedures using pancreatobiliary endoscopy.A large-diameter metallic stent can significantly extend the patency period rather than a plastic stent for extrahepatic biliary stricture.;However,the optimal drainage for the hilar biliary obstruction is still controversial.

Efficacy and safety of single-bolus tenecteplase compared with front-loaded alteplase in Chinese patients with acute myocardial infarction

Following ST-segment elevation myocardial infarction(STEMI), early and complete epicardial reperfusion is associated with improved survival.……

Safety and efficacy of trimodality therapy in patients undergoing extrapleural pneumonectomy

Malignant pleural mesothelioma （MPM） is a rare but rapidly deadly disease （1）. Macroscopic complete resection （MCR） is the goal of surgery （2）. MCR seems to have the most significant impact on survival in patients undergoing multimodality treatment for MPM. The role of surgical resection in the management of MPM remains controversial. The selection criterion to perform either extrapleural pneumonectomy （EPP） or extended/radical pleurectomy/ decortication （PD） rely not only on the cardio-pulmonary status of the patient, tumor stage and intraoperative findings but is strongly dependent also on surgeons＇ decision and philosophy. This is reflected by a recent survey of opinions and beliefs among 802 thoracic surgeons, in which EPP was believed to be more effective than PD （3）. Nonetheless, either surgery might achieve MCR.

Safety and efficacy of the SeparGateTM balloon-guiding catheter in neurointerventional surgery:A prospective,multicenter,single-arm clinical trial

Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy.The primary endpoint was immediate procedural success rate in flow arrest,device delivery,and withdrawal.The efficacy endpoints were intraoperative product performance,including rigidity,smoothness,fracture resistance of the catheter wall,catheter push performance,compatibility and radiopaque display,integrity,adhesion thrombus after withdrawal and balloon rupture.The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration.Result:A total of 129 patients were included;of them,128 were analyzed in the full analysis set(FAS)and per protocol set(PPS).Immediate procedural success was achieved in 97.7%of patients with FAS and PPS.The lower bound of the 95%confidence interval was 94.6%,higher than the preset efficacy margin of 94%.Device-related adverse events occurred in 2(1.6%)cases.One was mild adverse event of vasospasm,which resolved spontaneously.The other was serious adverse event of dissection aggravation,which was treated with stenting angioplasty.No device defects were observed.Conclusion:In neurointerventional surgery,the SeparGateBGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.

Safety and efficacy of acute normovolemic hemodilution during liver surgery: a Meta-analysis

Objective The aim of this study was to evaluate the safety and efficacy of acute normovolemic hemodilution(ANH) during liver surgery.Methods Structured searches of the Pub Med,Chinese Biological Medicine Database,and Cochrane Library electronic databases were performed,followed by a meta-analysis of outcomes,including intraoperative blood transfusion(s),intraoperative bleeding,postoperative hematocrit(Hct) levels,postoperative prothrombin time(PT),and number of patients who underwent transfusions during liver surgery.Results In total,14 eligible studies were included in the meta-analysis,which revealed that ANH for liver resection was associated with a reduction in intraoperative blood transfusions [weighted mean difference(WMD)-1.99;95% confidence interval(CI)-2.82 to -1.16;P<0.00001].The ANH group experienced less intraoperative bleeding(WMD -72.81;95% CI -136.12 to -9.50;P<0.00001) and exhibited a lower postoperative Hct level(WMD -3.38;95% CI -7.14 to -0.67;P<0.00001) than the control group.Moreover,meta-analysis revealed that postoperative prothrombin time was not affected by ANH(WMD -0.02;95% CI -0.18 to -0.32;P=0.65).Finally,the number of patients requiring allogeneic transfusion was significantly smaller in the ANH group than in the control group(odds ratio 0.13;95% CI 0.09 to 0.18;P=0.24).Conclusion Results of the present meta-analysis indicated that ANH can reduce intraoperative bleeding and the need for blood transfusions.In addition,ANH did not negatively affect the coagulation system after surgery;therefore,ANH appears to be safe and effective during liver surgery.

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.

Efficacy and Phytotoxicity Trial of Different Dosages of 4% Nicosulfuron SC on Weeds in Corn Fields

[Objective]The paper was to study efficacy and phytotoxicity of different dosages of 4% nicosulfuron on weeds in corn fields.[Method]With summer corn variety Zhengdan 958commonly used in field production in Hengshui area of Hebei Province of China as the test material,different dosages（1 050,1 500 and 1 950mL/hm2）of corn postemergence herbicide 4% nicosulfuron SC were sprayed during five-leaf stage of corn,and the treatments with water spraying and manual weeding were set as controls.The effects of different dosages of 4% nicosulfuron SC on weed control efficacy and safety and yield of corn were analyzed in order to determine the optimal dosage.[Result]Spraying 4% nicosulfuron SC with dosage of 1 500mL/hm2 during five-leaf stage of corn not only had better control effect against various weeds,but also did not produce phytotoxicity on corn,and the yield of corn was higher.[Conclusion]The study provided scientific information for using 4% nicosulfuron to eradicate weeds in corn fields.

Stereotactic body radiotherapy combined with sintilimab in patients with recurrent or oligometastatic hepatocellular carcinoma: A phase Ⅱ clinical trial

BACKGROUND Stereotactic body radiotherapy(SBRT)and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma(HCC)in retrospective studies.AIM To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC.METHODS This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression.The primary endpoint was progression-free survival(PFS).RESULTS Twenty-five patients were enrolled from August 14,2019,to August 23,2021.The median treatment duration was 10.2(range,0.7-14.6)months.SBRT was delivered at a median dose of 54(range,48-60)Gy in 6(range,6-10)fractions.The median follow-up time was 21.9(range,10.3-39.7)mo,and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1.The median PFS was 19.7 mo[95%confidence interval(CI):16.9-NA],with PFS rates of 68%(95%CI:52-89)and 45.3%(95%CI:28-73.4)at 12 and 24 mo,respectively.The median overall survival(OS)was not reached,with OS rates of 91.5%(95%CI:80.8-100.0)and 83.2%(95%CI:66.5-100.0)at 12 and 24 mo,respectively.The 1-and 2-year local control rate were 100%and 90.9%(95%CI:75.4%-100.0%),respectively.The confirmed objective response rate and disease control rate was 96%,and 96%,respectively.Most adverse events were graded as 1 or 2,and grade 3 adverse events were observed in three patients.CONCLUSION SBRT plus sintilimab is an effective,well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.

Clinical evidence of neoadjuvant immunotherapy for resectable locally advanced esophageal carcinoma:A systematic review

Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEc by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC.Methods:PubMed,Cochrane Library,Embase and ClinicalTrials.gov were searched from inception until June 1st,2023,for available reports to perform a meta-analysis.The primary endpoints were RO resection,objective response rate(ORR),pathological complete response(pCR)and major pathological response(MPR),as well as treatment-related adverse events(AEs)and postoperative complications.The Stata 14.0 software was employed to estimate pooled effect size.Results:A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria.Meta-analysis showed that,among these patients with rlaEC,the pooled R0 resection rate was 97.0%(95%CI:94.0%-99.0%),the p0oled ORR was 70.0%(95%CI:64.0%-76.0%),the p0oled pCR and MPR rate were 34.0%(95%CI:29.0%-39.0%)and 56.0%(95%CI:47.0%-65.0%)respectively.The incidence of main treatment-related AEs and postoperative complications was about 6%-45% and 8%-19% respectively.Conclusions:Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy.But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase II randomized controlled clinical trials.

Microwave Ablation versus Laser Ablation in Occluding Lateral Veins in Goats

Increasing number of endovenous techniques are available for the treatment of saphenous vein reflux and endovenous laser ablation（EVLA） is a frequently used method. A newly developed alternative, based on thermal therapy, is endovenous microwave ablation（EMA）. This study evaluated the effect of the two procedures, in terms of coagulation and histological changes, in occluding lateral veins in goats. Twelve animals were randomized into two group, with 6 treated with EMA（EMA group）, and the rest 6 with EVLA（EVLA group）. Results of coagulation, including coagulation, fibrinolysis and platelet activation, were assessed at three or four different time points： before, immediately after, 24 h（and 48 h） after ablation. The diameter change, a measure of efficacy, was ultrasonographically measured before and 1 month after the ablation. Histological changes were grossly and microscopically evaluated immediately, 1 and 3 month（s） after the ablation. The length of the ablated vein and preoperative average diameter were comparable between the two groups. In both EMA and EVLA groups, several coagulation parameters, fibrinolysis and platelet activation parameters only underwent slight changes. Ultrasound imaging displayed that the diameter reduction of the veins treated by EMA was significantly larger than by EVLA, in consistent with the results of macroscopic examination. Microscopic examination revealed necrosis and thickening of the vein wall, and occlusion of the lumen within 3 months after ablation in both EMA and EVLA groups. It is concluded that EMA is a minimally invasive therapy, which appears to be safe and effective for treatment of lateral veins in goats.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients： A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China

Background：High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia,and a domestically developed pacemaker will help lower the burden.This study aimed to evaluate the safety and efficacy ofQinming8631 DR （Qinming Medical,Baoji,China）,the first domestically developed dual-chamber pacemaker of China,compared with a commercially available pacemaker Talos DR （Biotronik,Berlin,Germany） in Chinese patients.Methods：A prospective randomized trial was conducted at 14 centers in China.Participants were randomized into trial （Qinming8631 DR） and control （Talos DR） groups.Parameters of the pacing systems were collected immediately after device implantation and during follow-ups.The effective pacing rate at 6-month follow-up was recorded as the primary end point.Electrical properties,magnet response,single-and double-pole polarity conversion,rate response function,and adverse events of the pacing system were analyzed.The Cochran-Mantel-Haenszel Chi-square test,paired t-test,and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data.Results：A total of 225 patients with a diagnosis ofbradyarrhythmia and eligible for this study were randomly enrolled into the trial （n =113） and control （n =112） groups.They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity.Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set （81.4% vs.79.5%,P =0.712 and 95.4% vs.89.5%,P =0.143,respectively）.In both data sets,noninferiority of the trial group was above the predefined noninferiority limit（-9.5%）.Conclusions：This study established the noninferiority ofQinming8631 DR to Talos DR.The safety and efficacy ofQinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Respiratory support for severe acute respiratory syndrome: integration of efficacy and safety

Severe acute respiratory syndrome （SARS） is an acute respiratory illness caused by infection with the SARS virus. The most obvious clinical characteristic of SARS is rapidly progressive pneumonia, and about 20% patients need intensive care due to acute lung injury （ALI） and acute respiratory distress syndrome （ARDS）.1-3 In the absence of effective drugs for SARS, supportive care, especially respiratory support techniques （RSTs）, is of primary importance. On the other hand, offering RSTs to SARS patients may carry a high-risk of infection to healthcare workers because of the high infectivity of SARS. Therefore, the strategy of RSTs for SARS should be the integration of efficacy and safety. In this issue of the Chinese Medical Journal, an article from Hong Kong has retrospectively compared both the safety and efficacy of noninvasive positive pressure ventilation （NIPPV） with that of invasive mechanical ventilation （IMV） in the treatment of respiratory failure in SARS.

Analysis of the effective dose of ultraviolet light in corneal cross-linking

AIM: To analyze the efficacy of ultraviolet (UV) light initiating corneal cross-linking (CXL). METHODS: The time-dependent absorption of UV light due to the depletion of the initiator (riboflavin) was calculated. The effective dose of CXL with corneal surface covered by a thin layer of riboflavin was derived analytically. The cross linking time was calculated by the depletion level of the riboflavin concentration. A comprehensive method was used to derive analytic formulas. RESULTS: The effective dose of CXL was reduced by a factor (R) which was proportional to the thickness (d) and concentrations (C-0) of the riboflavin surface layer. Our calculations showed that the conventional dose of 5.4 J/cm(2) had a reduced effective dose of 4.3 and 3.45 J/cm(2), for d was 100 and 200 pm, respectively, and C-0=0.1%. The surface cross linking time was calculated to be T*=10.75s, for a depletion level of 0.135 and UV initial intensity of 30 mW/cm(2). The volume T* was exponentially increasing and proportional to exp (bdC(0)), with b being the steady state absorption coefficient. CONCLUSION: The effective dose of CXL is reduced by a factor proportional to the thickness and concentrations of the riboflavin surface layer. The wasted dose should be avoided by washing out the extra riboflavin surface layer prior to the UV light exposure.

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

Can ＂Hybrid stent implantation＂ improve long-term safety without adversely affecting efficacy when treating multilesion coronary artery disease in the drug-eluting stent era？

Background Though drug-eluting stent （DES） almost solved a problem of restenosis, safety issues related to stent thrombosis are still the major concern of DES. We hypothesized that hybrid stent implantation may decrease the use of DES, probably improving the long-term safety but not affecting efficacy adversely when treating multilesion coronary artery disease in the DES era. Methods From April 2004 to October 2006, 848 patients with multilesion disease underwent hybrid stent implantation. During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital. According to propensity score matching, we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study. We obtained the 24-month clinical outcome including death, myocardial infarction （MI）, thrombosis, target lesion revascularization （TLR）, target vessel revascularization （TVR）, and major adverse cardiac events （MACE, the composite of death, MI, and TVR）. We used Cox＇s proportional-hazard models to assess relative risks of all the outcome measures after propensity match. Results At 24 months, patients in the hybrid stent implantation group showed a significantly higher risk of TLR （8.39% vs. 3.28%, HR2.38, 95% Cl. 1.50-3.70）, TVR （11.07% vs. 6.32%,/-/R 1.61, 95% Cl. 1.15-2.27） and MACE （13.75% vs. 8.75%, FIR 1.37, 95% Cl. 1.02-1.85）. No significant difference was apparent in terms of mortality （1.22% vs. 1.70%, HR 0.55, 95% Cl. 0.24-1.25）, MI （1.95% vs. 2.31%, HR0.73, 95% Cl. 0.37-1.42）, or thrombosis （definite＋probable） （0.73% vs. 1.58%, HR0.40, 95% Cl. 0.15-1.05）. Conclusions In patients with multilesion coronary artery disease, the exclusive DES implantation was associated with significantly lower risks of TLR, TVR and MACE, and the hybrid stent implantation did not result in any significant improvements regarding safety issues. Prospective studies are needed to confirm our results.

Efficacy and safety of evolocumab in reducing lipids and cardiovascular events

Background Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 （PCSK9）, significantly reduced low-density lipoprotein （LDL） cholesterol levels in short-term studies. We con- ducted two extension studies to obtain longer-term data.