[Research progress in autophagy in the development of pulp inflammation and dental pulp injury reparation and regeneration].

Pulpitis is an infectious disease characterized by persistent inflammation of dental pulp and severe pain of patients, root canal treatment increases the risk of tooth fracture, discoloration and reinfection. Therefore, pulp injury repair and pulp regeneration become the new targets of pulpitis treatment. Autophagy is considered as an important defense and protective mechanism, thus plays an important role in preventing the host from excessive inflammatory reaction. There are few reports on the regulative mechanisms and therapeutic strategies of autophagy on pulp inflammation progression, therefore, this paper reviewed the role of autophagy on the progression of pulpitis, also reviewed the research progress of autophagy on dental pulp injury repair and regeneration, aiming to provide theoretical support for further research and clinical application.

[The association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices].

Objective: To investigate the association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices. Methods: The cirrhotic patients with esophagogastric varices diagnosed in the People's Hospital of Zhengzhou University from January 2017 to March 2023 were retrospectively collected. The patients were divided into thrombotic group and non-thrombotic group according to the presence or absence of portal vein thrombosis. The failure rate of endoscopic treatment and rebleeding rate in different periods were compared between the two groups. Receiver operating characteristic (ROC) curve was used to select the best cutoff value of gastric varicose diameter that affected total rebleeding during follow-up in both groups. The influencing factors of rebleeding within 12 and 36 months in both groups were analyzed, and the influencing factors of rebleeding within 36 months in thrombus group were further analyzed. Results: A total of 106 patients were enrolled, including 53 patients in the thrombotic group [male 37, female 16, aged 18-78 (54±13) years] and 53 patients in the non-thrombotic group [male 37, female 16, aged 27-83 (55±12) years]. The follow-up time of the two groups were (20±15) and (25±15) months, respectively. The total rebleeding rate in the thrombotic group was higher than that in the non-thrombotic group [30.2% (16/53) vs 13.2% (7/53), P˂0.05]. The rebleeding rates within 6, 12, 24 and 36 months in the thrombotic group were higher than those in the non-thrombotic group [18.9% (10/53) vs 5.7% (3/53), 18.9% (10/53) vs 5.7% (3/53), 28.3% (15/53) vs 9.4% (5/53), 30.2% (16/53) vs 11.3% (6/53), all P˂0.05]. The best cut-off value of the diameter of gastric varices that affects the total rebleeding in the two groups was 10.4 mm (10 mm was selected as the best cut-off value for the convenience of practical clinical application). Hemoglobin ˂ 85 g/L (HR=0.202, 95%CI: 0.043-0.953, P=0.043), 10 mm ˂ the diameter of GV ≤ 15 mm (HR=5.321, 95%CI: 1.161-24.390, P=0.031) and endoscopic variceal ligation combined with endoscopic tissue adhesive injection (EVL+ETAI) (HR=7.172, 95%CI: 1.910-26.930, P=0.004) were the risk factors for the first gastroesophageal variceal rebleeding within 12 months after non-urgent endoscopic treatment. EVL+ETAI (HR=3.811, 95%CI: 1.441-10.084, P=0.007) and portal vein thrombosis (HR=4.026, 95%CI: 1.483-10.932, P=0.006) were the risk factors for the first gastroesophageal variceal rebleeding within 36 months after non-urgent endoscopic treatment. The study found that, 10 mm ˂ the diameter of GV ≤ 15 mm (HR=7.503, 95%CI: 1.568-35.890, P=0.012) was the risk factor for rebleeding within 36 months in the thrombotic group. Conclusion: Portal vein thrombosis is a risk factor for rebleeding after non-urgent endoscopic treatment of esophagogastric varices.

[Bilateral visual pathway invasion of occipital astrocytoma: a case report].

A 33-year-old female presented to the ophthalmology clinic with right periorbital redness and pain for 12 hours. CT revealed right optic nerve thickening and enlargement. Cranial MRI demonstrated abnormalities in the corpus callosum, bilateral hippocampi, thalamus, basal ganglia, temporal-parietal lobes, and the left frontal lobe. Ocular B-scan ultrasound showed elevated optic disc and high echogenic signals in the right vitreous cavity. The patient had a history of surgical resection, radiation therapy, and chemotherapy for a left occipital glioma two years prior, with pathology indicating astrocytoma (World Health Organization Grade Ⅱ). Combining the patient's history and diagnostic findings, the confirmed diagnosis is bilateral occipital astrocytoma with invasion into the right transverse sinus, bilateral optic pathways involvement related to the left occipital astrocytoma, and seeding of astrocytoma in the right vitreous cavity.

[Comparison of the impact of orthodontic treatment on pulp volume in adolescents and adults].

Objective: To compare the impact of orthodontic treatment on pulp volume in adolescents and adults. Methods: Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results: Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P (t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC (t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P (t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm3, respectively (t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment (t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively (t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 (t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P (r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P (r=0.11, P>0.05). Conclusions: The effect of orthodontic treatment on pulp volume in adolescents and adults were different.

[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

[Clinical value of arterial stiffness assessment on risk prediction of vascular stiffness in the octogenarian elderly].

Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.

[Analysis of China's influenza vaccination policy based on the model of "behavioural and social drivers of vaccination"].

This article uses the "behavioural and social drivers of vaccination" model released by the World Health Organization (WHO) in 2022 to analyze influenza vaccine policy documents issued by the state and governments. This indicates that the current influenza vaccination policy in China has paid some attention to "publicity and mobilization", but it still pays insufficient attention to "vaccination convenience". It is recommended to continue to strengthen publicity and mobilization, explore ways to improve the convenience of vaccination, formulate corresponding plans to improve the convenience of vaccination, scientifically set vaccination rate targets, and encourage areas with conditions to carry out free vaccination projects for key populations.

[The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study].

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

Retraction Note: LncRNA BRE-AS1 acts as a tumor suppressor factor in bladder cancer via mediating STAT3.

The article "LncRNA BRE-AS1 acts as a tumor suppressor factor in bladder cancer via mediating STAT3", by L. Zhang, B. Liu, Q.-H. Deng, J.-X. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5320-5328-DOI: 10.26355/eurrev_202005_21314-PMID: 32495865 has been retracted by the Editor in Chief for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/F4A75D571A58C9005B703B2B8C4A8E). In particular, concerns were raised about Figures 2D and 5A as the figures result to overlap with previously published papers. The paper has been identified with the "The Clear Skies Papermill Alarm". The Editorial Office has contacted the corresponding author of the article to provide a reply to the comments on PubPeer and the raw data. Still, the journal has yet to receive a reply. Therefore, considering the comments released on PubPeer and the lack of response from authors, the Editor in Chief no longer relies on the data presented and decided to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21314.

[Pathologic features of paraspinal muscle biopsies in patients with adolescent idiopathic scoliosis].

OBJECTIVE: To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology. METHODS: Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically. RESULTS: Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers. CONCLUSION: The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.

[Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients].

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

[Application of bridging study design in preventive vaccine clinical trials].

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.

[Five-year immunity persistence following immunization with haemophilus influenzae type b conjugate vaccine].

Objective: To evaluate the immunity persistence five years later after immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in healthy infants/children aged 3 months to 5 years in China. Methods: The children were subjects who completed the whole-schedule immunization in the phase Ⅲ clinical trial in Lianshui county of Jiangsu povince was selected for the collection of blood samples at 5 years after vaccination from November to December, 2019. The enzyme-linked immunosorbent assay (ELISA) was used to detect Hib polyribosyl-ribitol-phosphate antibody (anti-Hib-PRP), and the long-term/short-term protection rate, geometric mean concentration (GMC) and geometric mean concentration increase fold (GMFI) of serum anti-Hib-PRP were calculated. Results: A total of 580 children were enrolled in this study, of which 158, 207 and 215 belonged to 3-5 month age group, 6-11 month age group and 1-5 year age group, respectively. The short-term (≥0.15 µg/ml)/long-term (≥1.0 µg/ml) protection rates of serum anti-PRP in the three groups after immunization were 89.24%, 90.34% and 98.60%, respectively; the GMC were 3.95 µg/ml, 3.11 µg/ml and 10.01 µg/ml respectively, and the GMFI were 29.04, 11.01 and 3.26 respectively. Conclusions: Hib conjugate vaccine can still have good immunogenicity after 5 years of primary immunization in healthy infants/children aged 3 months to 5 years in China.

[Effect evaluation of "Smoking cessation: Doctor first"program in China].

Objective: To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff. Methods: From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into"Smoking cessation: Doctor first"program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated. Results: The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking is not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully. Conclusion: "Smoking cessation: Doctor first"program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.

[Impact of prolonging dual antiplatelet therapy on long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus undergoing drug-eluting stent implantation].

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (1324 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 1324 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 1324 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 1324 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.

[A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting].

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.

[Effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits].

Objective: To study the effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits. Methods: Thirty-two 3.5-month-old New Zealand rabbits were randomly divided into low-intensity group, medium-intensity group, high-intensity group and control group, with 8 rabbits in each group. The rabbits in the experimental group were subjected to hind limb vibration load test for 45 days. The vibration intensity of the high intensity group was 12.26 m/s(2), the medium intensity group was 6.13 m/s(2), and the low intensity group was 3.02 m/s(2) according to the effective value of weighted acceleration[a(hw (4))] for 4 hours of equal energy frequency. The control group was exposed to noise only in the same experimental environment as the medium-intensity group. The noise levels of each group were measured during the vibration load experiment. After the test, the mRNA expression of mitochondrial fusion gene (Mfn1/Mfn2) and fission gene (Fis1, Drp1) by RT-PCR in the skeletal muscles were measured and the ultrastructure of the skeletal muscles were observed in high intensity group. Results: The mRNA expression of mitochondrial in the skeletal muscle tissues of control group, low intensity group, medium intensity group and high intensity group were Mfn1: 3.25±1.36, 3.85±1.90, 4.53±2.31 and 11.63±7.68; Mfn2: 0.68±0.25, 1.02±0.40, 0.94±0.33 and 1.40±0.45; Fis1: 1.05±0.62, 1.15±0.59, 1.53±1.06 and 2.46±1.51 and Drp1: 3.72±1.76, 2.91±1.63, 3.27±2.01 and 4.21±2.46, respectively. Compared with the control group, the expressions of Mfn1 mRNA, Mfn2 mRNA and Fis1 mRNA in the high-intensity group increased significantly (P<0.05) , and the expressions of Mfn2 mRNA in the medium-intensity group and the low-intensity group increased significantly (P<0.05) . Compared with the control group, the ultrastructure of skeletal muscle of high intensity group showed mitochondrial focal accumulation, cristae membrane damage, vacuole-like changes; Z-line irregularity of muscle fibers, and deficiency of sarcomere. Conclusion: Vibration must be lead to the abnormal mitochondrial morphology and structure and the disorder of energy metabolism due to the expression imbalance of mitochondrial fusion and fission genes in skeletal muscles of rabbits, which may be an important target of vibration-induced skeletal muscle injury.

Effects of feeding solid-state fermented wheat bran on growth performance and nutrient digestibility in broiler chickens.

Solid-state fermentation has been used to improve the nutritive value of feed ingredients. In the present study, we investigated the effects of solid-state fermented wheat bran (FWB) on growth performance and apparent digestibility in broiler chickens. We measured the growth performance (ADFI, ADG, feed conversion, livability, and European performance efficiency factor) over 38 d in chicks fed a corn-soybean meal control diet (CON) or CON plus wet FWB (25 g/kg [T1]; 50 g/kg [T2]); or T1 plus 3 g/kg (T3); or T2 plus 6 g/kg (T4) soybean oil). The same diets were used to determine nutrient availability in chicks aged 20 d. Regression equations for AME and AMEn were obtained using 20-day-old chicks fed either the corn-soybean meal basal diet only or basal diet partially substituted with 50, 150, or 300 g/kg DM FWB. Diets containing 25 or 50 g/kg wet FBW did not affect the growth performance of broiler chickens, nor the apparent DM, energy, and nitrogen digestibility of the feeds, compared with the control diets (all P > 0.05). Further supplementation with oil did not improve the growth performance of broiler chickens compared with controls or chickens fed FBW. However, chickens fed diets containing soybean oil (T3 or T4) had lower (P = 0.005 and P = 0.040, respectively) apparent DM and energy digestibility than the control and FWB groups. The regression equations for AME and AMEn with the substitution of FWB produced values of 1,854.3 and 1,743.9 kcal/kg DM, respectively, and the equations were Y = 1854.3X + 52.7 (R2 = 0.971, n = 24, P < 0.001), and Y = 1743.9X + 44.6 (R2 = 0.978, n = 24, P < 0.001), respectively. Supplementation with wet FWB did not affect the growth performance of broiler chickens. Therefore, FWB is a suitable feed component for broilers.

[Application of cluster randomization design in vaccine clinical trials].

When the coverage of the vaccinated people reaches a certain percentage of the population, the herd protection will protect the unvaccinated persons. However, the traditional clinical evaluation of vaccines performing individual randomized design fails to evaluate the herd protection of vaccines. Compared with the individual randomized design, the cluster-randomized design can determine the overall protection by the vaccine more comprehensively. It has become increasingly common to perform a cluster-randomized design in clinical trials of vaccines in Phase Ⅲ and Ⅳ clinical trials. However, little is known about the application of cluster randomized design in vaccine clinical trials in China. We, at this moment, do a review of the application of random cluster design in vaccine clinical trials and provide references for future research in China.