Stroke has characteristics of high incidence, disability, mortality and recurrence rates. Ischemic stroke (IS) is the most prevalent type of stroke. Early management of risk factors associated with IS, such as cholesterol level, has a beneficial impact on improving long-term prognosis. Proprotein converting enzyme subtilin kexin type 9 (PCSK9) is a circulating enzyme that regulates low density lipoprotein receptor (LDLR), and PCSK9 inhibitor can reduce serum low density lipoprotein cholesterol by blocking the PCSK9 binding to LDLR; therefore, PCSK9 inhibitor, as a new type of lipid-lowering drug, shows great potential in IS prevention and treatment. This article summarizes the physiological functions of PCSK9, clinical application of PCSK9 inhibitor and role of PCSK9 inhibitor in IS pathologic, aiming to offer novel suggestions for improving short-term and long-term prognoses of individuals with IS.

BACKGROUND:The gluteus medius not only abducts the hip joint,but also plays an important role in limiting the external movement of the femoral head.At present,there is a lack of research on the correlation between gluteus medius status and non-traumatic femoral head necrosis. OBJECTIVE:To investigate the relationship between the gluteus medius width ratio and the medial space ratio of the hip joint and the progression of non-traumatic femoral head necrosis,and to explore the effect of gluteus medius atrophy on the surface and necrotic zone stress of the femoral head necrosis through finite element analysis. METHODS:Retrospective analysis of unilateral non-traumatic femoral head necrosis patients admitted to Third Affiliated Hospital of Guangzhou University of Chinese Medicine was performed.All patients were followed up for an average of more than 2 years.They were divided into a collapsed group and a non-collapsed group based on whether there was collapse of the femoral head during the follow-up.Medial space ratio,gluteus medius width ratio,Sharp angle,gluteus medius length ratio,and gluteus medius activation angle were measured and calculated.The differences in these indicators were compared between the two groups.At the first visit and follow-up at 3,6,12,and 24 months,the medial space ratio and gluteus medius width ratio were measured and calculated to explore the changes of these two indicators in the course of non-traumatic femoral head necrosis.In addition,using three-dimensional finite element analysis,a Japanese Investigation Committee classification C1 type femoral head necrosis model was constructed based on CT data.At the same time,based on MRI data,a model of the gluteus medius muscle was constructed and divided into a gluteus medius muscle atrophy group(gluteus medius width ratio:74%-76%)and a gluteus medius muscle normal group(gluteus medius width ratio:94%-96%).Each group constructed 10 models,with 6 degrees of freedom of the distal femur constrained to zero.600 N pressures were applied along the Z-axis to the upper surface of the sacrum.The stress distribution,maximum stress values on the surface and necrotic area of the femoral head,and the maximum displacement of the necrotic area were compared between two groups of models. RESULTS AND CONCLUSION:(1)A total of 153 patients(67 males and 86 females)with 153 hips were included in this study.(2)At the 24-hour follow-up,the medial space ratio of the collapsed group was significantly higher than that of the non-collapsed group(P<0.05).The gluteus medius width ratio of the collapsed group was significantly lower than that of the non-collapsed group(P<0.05).There was no statistically significant difference in Sharp angle,gluteus medius activation angle,and gluteus medius length ratio between the two groups(P>0.05).(3)Since the follow-up time exceeded 3 months,the gluteus medius width ratio of the collapsed group was lower than that of the non-collapsed group(P<0.05).Since the follow-up time exceeded 12 months,the medial space ratio of the collapsed group was higher than that of the non-collapsed group(P<0.05).(4)Pearson correlation analysis showed a significant positive correlation between follow-up time and medial space ratio in the collapsed group(P<0.05),and a significant negative correlation between follow-up time and gluteus medius width ratio(P<0.05).The regression coefficient of gluteus medius width ratio was larger than that of medial space ratio.(5)The group with middle gluteal muscle atrophy showed significant stress concentration on the surface of the femoral head,and the stress zone was significantly located on the outside.The maximum stress on the surface of the femoral head in the group with middle gluteal muscle atrophy was significantly greater than that in the group with normal middle gluteal muscle(P<0.05).There was significant stress concentration in the necrotic area of the middle gluteal muscle atrophy group,and the maximum stress was located at the edge of the necrotic area.The maximum stress and maximum displacement in the necrotic area of the middle gluteal muscle atrophy group were significantly greater than those of the normal group(P<0.05).(6)It is indicated that gluteus medius width ratio is an effective indicator for evaluating changes in gluteal muscle atrophy.In the progression of non-traumatic femoral head necrosis,atrophy of the gluteus medius muscle first occurs,followed by widening of the medial hip joint space.The mechanical mechanism may be that the atrophy of the gluteus medius muscle affects the stability of the hip joint,leading to external displacement of the femoral head,and increasing stress and displacement on the surface and necrotic area of the femoral head.

Objective:To study the phenotype and genotype distribution of Yersinia pestis ( Y. pestis) in different natural foci of plague in China, so as to provide scientific basis for plague prevention and control. Methods:A total of 2 184 strains of Y. pestis isolated from different time periods, regions, hosts and vectors in 11 plague natural foci of China since 1943 were selected for biochemical type identification, glycolysis test, virulence factor test [capsule antigen (F1), pesticin Ⅰ (Pst Ⅰ), virulence antigen factor (VWa), pigmentation factor (Pgm)], different region (DFR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Results:There were 16 biochemical types of Y. pestis in the natural foci of plague in China, and each biochemical type showed obvious regional distribution in each foci. Most strains were positive for ass hide glue glycolysis (89.79%, 1 961/2 184), maltose (80.13%, 1 750/2 184), glycerol (94.23%, 2 058/2 184), and denitrification (82.78%, 1 808/2 184), and negative for rhamnose (88.78%, 1 939/2 184) and melibiose (85.62%, 1 870/2 184). Virulence factor test results showed that 99.95% (2 183/2 184) of Y. pestis were F1 positive; 99.73% (2 178/2 184) of Y. pestis can produce Pst Ⅰ; 73.31% (1 601/2 184) of Y. pestis were VWa positive and 26.69% (583/2 184) were VWa negative; Pgm positive strains accounted for 72.62% (1 586/2 184), Pgm negative strains accounted for 21.52% (470/2 184), and Pgm mixed type strains accounted for 5.86% (128/2 184). According to DFR typing results, there were 52 genotypes in 2 184 strains of Y. pestis, of which 19 were major genotypes and 33 were minor genotypes. CRISPR typing revealed 16 major genotypes, of which 7 were newly discovered. Conclusion:The phenotypes and genotypes of Y. pestis in various natural foci of plague in China are diverse and have geographical distribution characteristics.

Abstract: Objective To observe the phenotypic characteristics of 3 wild-type plague phages under different experimental environments, providing scientific evidence for the identification of phage biological characteristics and the study of their interaction with host bacteria in the future. Methods The sensitivity of 3 wild-type plague phages were detected by using liquid culture method, emisolid medium method and micro-liquid culture method based on OmniLog TM microbial identification system. Results The growth result based on LB liquid medium showed that the growth of plague phage 476 for 20-24 hours at both 28 ℃ and 37 ℃was better than that of plague phages 087 and 072204 at 37 ℃, and the growth of plague phages 087 was better than that of plague phages 072204 at 37 ℃. With the attenuated plague bacterium EV76 as the host bacterium, phage 476 was able to form visible plaque on double-layer agar medium for 20-20 hours at both 28 ℃ and 37 ℃, phages 087 and 072204 were only able to form opaque plaque on double-layer agar medium for 20-24 hours at 37 ℃. The growth results based on OmniLogTM system showed that when plague phage was lysed in EV76 strain at 33 ℃, the first row appeared as a straight line with a peak of no more than 100 in the 96-well microplate curve chart. As the phage quantity decreased, the dilution plate appeared with growth curve similar to EV76 strain in turn, and the color of tetrazolium dyes in the experimental wells gradually deepened as the phage number decreased and the host bacteria number increased. Therefore, it indicates that phage 476 was sensitively at both 28 ℃ and 37 ℃, while phage 087 and 072204 were temperature-dependent only at 37 ℃ to attenuated plague bacterium EV76. Conclusions The lysing ability of 3 wild-type plague phages are temperature-dependent, and the growth results are consistent under the three experimental conditions.

Objective     To systematically evaluate the safety, efficacy, and economics of intracardiac echocardiography (ICE) versus transesophageal echocardiography (TEE) in left atrial appendage occlusion (LAAO). Methods     PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Database were systematically  searched to collect relevant studies on comparing ICE and TEE-guided LAAO from inception to June 15th, 2022. Two reviewers independently screened the literatures, extracted the data, and assessed the risk of bias of the included studies. Meta-analyses were performed using RevMan 5.3 and R 4.0.3. Retrospective cohort studies were excluded for sensitivity analysis. Subgroup analyses were performed based on the types of occluder and ICE catheter. Results     A total of 14 studies with 6 599 patients were included. Meta-analyses showed no statistical differences in technical success rate, overall complications, device embolization, peri-device leakage, device-related thrombus, stroke, vascular complications, bleeding, operation time, fluoroscopy time, or contrast agent volume between the ICE and TEE-guided LAAO. The total in-room time (MD=–33.47 min, 95%CI –41.20 to –25.73, P<0.000 01) and radiation dosage (MD=–170.20 mGy, 95%CI –309.79 to –30.62, P=0.02) were lower in the ICE group than those in the TEE group, whereas the incidence of pericardial effusion/tamponade was higher than the TEE group (RR=1.57, 95%CI 1.01 to 2.45, P=0.048). Except for pericardial effusion/tamponade, subgroup analyses and sensitivity analysis showed similar results. The analysis based on the cost data from the United States showed comparable or even lower total costs for ICE versus TEE, but comparative domestic cost studies were lacking. Conclusion     Current evidence suggests that ICE-guided LAAO can reduce radiation dosage and total in-room time, and there is no statistical difference in the overall complication rate between the two groups. Owing to the limitations of sample size and quality of the included studies, the conclusion still needs to be verified by large sample size and high-quality randomized controlled trials.

Objective:To investigate the effects of superoxide dismutase 1 (SOD1) mutations G41D and G41S on the cognitive behavior of mice.Methods:The recombinant adeno-associated virus (rAAV) which overexpressed human SOD1WT, SOD1G41S, SOD1G41D and the blank virus without the target gene were constructed, then they were stereotaxic injected into mice bilateral medial prefrontal cortex (mPFC) area respectively.According to the difference of injected virus, they were divided into CONTROL group, SOD1WT group, SOD1G41S group and SOD1G41D group ( n=16 in each group). One month later, open field test, Y-maze spontaneous alternation experiment, three box social interaction experiment and trace fear conditioning test were conducted to observe the effect of mutant gene on cognitive behavior of mice. Results:In the open field test, the movement distance of SOD1WT group((39.67±6.04)m)was significantly higher than that of SOD1G41D group((28.47±6.92)m, P=0.034). In the Y-maze spontaneous alternations experiment, the number of arm entries and actual alternations of arm entries of SOD1WT group((40.56±10.12)times, (32.63±8.19)times)and SOD1G41S group((36.75±9.43)times, (29.06±8.32)times)were significantly higher than those of SOD1G41D group((24.50±11.30)times, (18.38±9.09)times, P<0.05). In the three-compartment social experiment, there was no statistical difference between the residence time of SOD1G41D group in the area containing mouse ((279.08±134.94) s) and the empty metal cage area ((218.54±125.63) s) ( t=1.313, P=0.199). SOD1WT group and SOD1G41S group showed no statistical difference in the residence time in the regions of the unfamiliar mouse 1((253.07±55.60)s, (253.20±57.61)s) and the unfamiliar mouse 2 ((243.44±55.33) s, (239.76±67.49) s) ( P>0.05), and SOD1WT group and SOD1G41S group presented new social barrier.In the test stage of trace fear condition task, the percentage of freezing time of SOD1G41S group was significantly higher than that of other experimental groups and CONTROL group ( P<0.05). Conclusion:SOD1G41S and SOD1G41D have significantly changed the cognitive behavior of mice, and the two types of mutations at the same site have significant differences in the cognitive behavior changes.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective: Understanding mental health status of students with learning disabilities in Beijing to provide a basis for mental health promotion of students with learning disabilities. Methods: By means of random cluster sampling, 5 787 enrolled students in grade one and grade two of 11 public junior middle schools in Beijing were selected as the survey subjects. A self designed questionnaire was used to investigate the students’ learning disabilities and mental health status through anonymous self filling. Results: About 11.6% students self reported learning disabilities. The proportions of students with learning difficulty in mathematical reasoning and calculation were higher, 44.1% and 40.7% respectively. The reported rate of mental health problems was 38.3%. The top four of the 10 symptoms were obsessive compulsive symptoms, learning pressure, emotional instability and anxiety(2.19±0.77)(2.17±0.99)(2.09±0.90)(2.07±1.08). Compared with students without learning disabilities, students with self reported learning disabilities had poorer mental health status(OR=1.47), and learning disabilities were related to most factors of mental health. Different types of learning disabilities were associated with different mental health factors. Conclusion Mental health problems of students with learning disabilities are higher than that of students without learning disabilities. It is necessary to strengthen the mental health support for students with learning disabilities and improve their mental health.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

The 28th International Conference on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Boston from December 8 to 10, 2017. The conference covered 23 topics, 102 special topics and 446 papers. This article briefly introduces some topics of the conference, involving basic research, clinical research and clinical trials. Among these, basic studies include genetics, cell biology and pathology, and superoxide dismutase1 gene ALS related pathology; clinical studies include the progression of ALS disease, cognitive behavioral disorders, and biological markers.