Objective:To compare the efficacy of internal fixation using cannulated screw combined with fibular allograft and internal fixation using cannulated screw alone in the treatment of femoral neck fracture in young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 75 young and middle-aged patients with femoral neck fracture admitted to the Third Hospital of Hebei Medical University from January 2020 to December 2022, including 44 males and 31 females, aged 34-56 years [(46.1±12.7)years]. According to Garden classification, 26 patients were classified as type II, 35 type III and 14 type IV. According to the Pauwels classification, 9 patients were classified as type I, 31 type II and 35 type III. Forty-nine patients were treated with internal fixation using three cannulated screws alone (cannulated screw group) and 26 with internal fixation using three cannulated screws combined with double-barrel fibular allograft (cannulated screw combined with bone grafting group). The operation time, intraoperative blood loss, length of hospital stay, and quality of fracture reduction were compared between the two groups. At 4, 8 months after operation and at the last follow-up, grading of femoral neck shortening, number of patients walking with crutches, Barthel index, and Harris hip function score were evaluated. The incidence of complications was measured at the last follow-up.Results:All the patients were followed up for 16-37 months [(23.2±4.5)months]. The operation time of the cannulated screw combined with bone grafting group was (86.3±16.1)minutes, longer than (76.9±20.8)minutes of the cannulated screw group ( P<0.05). The intraoperative blood loss was 100.0(50.0, 200.0)ml in the cannulated screw combined with bone grafting group, more than 50.0(50.0, 100.0)ml in the cannulated screw group ( P<0.01). There were no significant differences in the length of hospital stay or the quality of fracture reduction between the two groups ( P>0.05). At 4 months after operation, grading of the femoral neck shortening in the cannulated screw combined with bone grafting group [24 patients (92.3%) with grade 1, 2(7.7%) with grade 2, and 0(0.0%) with grade 3] was better than that in the cannulated screw group [18 patients (36.7%) with grade 1, 28(57.1%) with grade 2, and 3(6.2%) with grade 3] ( P<0.01). At 8 months after operation, grading of femoral neck shortening in the cannulated screw combined with bone grafting group [22 patients (84.6%) with grade 1, 3(11.5%) with grade 2, and 1(3.8%) with grade 3] was better than that in the cannulated screw group [13 patients (26.5%) with grade 1, 27(55.1%) with grade 2, and 9(18.4%) with grade 3] ( P<0.01). At the last follow-up, grading of femoral neck shortening in the cannulated screw combined with bone grafting group [19 patients (73.0%) with grade 1, 5(19.2%) with grade 2, and 2(7.6%) with grade 3] was better than that in the cannulated screw group [8 patients (16.3%) with grade 1, 31(63.2%) with grade 2, and 10(20.4%) with grade 3] ( P<0.01). At 4, 8 months after operation and at the last follow-up, 12(46.2%), 8(30.8%) and 5(19.2%) patients in the cannulated screw combined with bone grafting group and 38(77.6%), 27(55.1%) and 20(40.8%) patients in the cannulated screw group had to walk with crutches, respectively, showing significant difference between the two groups at the other two time points ( P<0.05 or 0.01) except for at the last follow-up ( P>0.05). The Barthel index values were 85.3±3.2, 90.3±4.3, and 95.3±3.9 in the cannulated screw combined with bone grafting group at 4, 8 months after operation and at the last follow-up, significantly higher than 80.8±7.3, 85.4±7.4, and 90.9±7.8 in the cannulated screw group ( P<0.05 or 0.01). The Harris hip scores were (87.0±2.9)points, (92.0±2.9)points and (91.3±2.4)points in the cannulated screw combined with bone grafting group at 4, 8 months after operation and at the last follow-up, significantly higher than (81.0±6.1)points, (85.7±5.8)points, and (89.6±2.0)points in the cannulated screw group ( P<0.01). At the last follow-up, the complication rate was 3.8%(1/26) in the cannulated screw combined with bone grafting group, significantly lower than 22.4%(11/49) in the cannulated screw group ( P<0.05). Conclusion:For femoral neck fractures in young and middle-aged patients, compared with internal fixation using cannulated screw alone, internal fixation using cannulated screw combined with fibular allograft has more advantages in correcting femoral neck shortening, restoring independent living activities and hip joint function, and reducing the incidence of complications despite its longer operation time and more intraoperative blood loss.

The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Objective:To establish a new model for the prediction of severe outcomes of COVID-19 patients and provide more comprehensive, accurate and timely indicators for the early identification of severe COVID-19 patients.Methods:Based on the patients’ admission detection indicators, mild or severe status of COVID-19, and dynamic changes in admission indicators (the differences between indicators of two measurements) and other input variables, XGBoost method was applied to establish a prediction model to evaluate the risk of severe outcomes of the COVID-19 patients after admission. Follow up was done for the selected patients from admission to discharge, and their outcomes were observed to evaluate the predicted results of this model.Results:In the training set of 100 COVID-19 patients, six predictors with higher scores were screened and a prediction model was established. The high-risk range of the predictor variables was calculated as: blood oxygen saturation <94 %, peripheral white blood cells count >8.0×10 9, change in systolic blood pressure <-2.5 mmHg, heart rate >90 beats/min, multiple small patchy shadows, age >30 years, and change in heart rate <12.5 beats/min. The prediction sensitivity of the model based on the training set was 61.7 %, and the missed diagnosis rate was 38.3 %. The prediction sensitivity of the model based on the test set was 75.0 %, and the missed diagnosis rate was 25.0 %. Conclusions:Compared with the traditional prediction (i.e. using indicators from the first test at admission and the critical admission conditions to assess whether patients are in mild or severe status), the new model’s prediction additionally takes into account of the baseline physiological indicators and dynamic changes of COVID-19 patients, so it can predict the risk of severe outcomes in COVID-19 patients more comprehensively and accurately to reduce the missed diagnosis of severe COVID-19.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:This paper aims to analyze the monitoring model of Canadian drug price monitoring mod-el based on the international reference price, and make reference for China. Methods: Through policy analysis and literature research, the system combs the specific Canadian practices of using the international reference prices for the drug price monitoring. Results:For the introduction of new drug prices, Canada uses the international median price comparison test, the highest international price comparison test, the treatment category comparison test and the inter-national treatment category comparison test. For the listed drugs, Canada calculates the international price ratio, and then carries out bilateral comparisons and multilateral comparisons to monitor the prices of drugs already on the mar-ket. At present, Canada has achieved effective monitoring of drug prices, that is to say, the introduction of new drug prices complies with the《Excessive Price Guide》;the patented drugs prices are lower than the designed international price;the price difference between the generic drug and the international level has gradually reduced. Conclusions:The Canadian experience is worth learning, and China should add legislative about drug price monitoring, learn from this experience to identify and monitor the varieties and establish the price monitoring and early warning mechanism with the international reference price as the warning indicator.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation.Limited to the standards of tumor tissue samples and detection methods,still some people can't receive target therapy following genetic guidance.This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation,who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital,analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.Results The objective response rate (ORR)was 52.8％ and the disease control rate (DCR) was 89.3％.The results showed that,patients with high CEA level before treatment responded better to TKIs (ORR 61.3％ vs 35.9％,DCR 95.2％ vs 74.4％,P＜0.001).Similar phenomena was found in patients with CEA decreased 1 month later (61.5％ vs 25％,P=0.002).Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo,P=0.027).To the opposite,PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo,P=0.029;9.0 mo vs 11.5 mo,P=0.023,respectively).Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1,normal baseline CYFRA21-1 and CEA decline predicted longer PFS.The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo,P=0.003;22.7 mo vs 55.0 mo,P＜0.001,respectively),while independent of CEA.Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma.While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.