ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳ_a and aristolochic lactam Ⅰ. Aristolochic acid Ⅳ_a has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.

Objective:To investigate the satisfaction of clinical interns to the department and teachers under the merging mode of standardized residency training and clinical practice, and to explore the feasibility to further implement the mode in clinical practice.Methods:Cluster sampling was used to design the scale, which included the importance attached by department to the teaching work, the rationality of the arrangement of practice content, the implementation of teaching activities, the quality of teaching activities, the status of out-department examination, the demonstration of medical ethics of teachers, the teaching attitude and knowledge lecturing of teachers, the revision of medical records and the guidance of skills operation, etc. The questionnaire survey was conducted among clinical interns in a hospital from July 2018 to June 2019. SPSS 22.0 was used to conduct t test or rank sum test of two independent samples, and the analysis of multiple groups of data was performed by means of variance analysis. Results:A total of 1 230 questionnaires were sent out, and 1 195 were returned, with an effective recovery rate of 97.15%. The overall satisfaction of interns was (9.62±0.39). The interns gave the highest evaluation on the medical ethics and medical style of the teacher (9.75±0.78), and the lowest evaluation on the teaching quality of all departments (9.52±1.15). There were significant differences among the evaluations ( F=7.30, P<0.001). Conclusion:Under the merging mode of standardized residency training and clinical practice management, all teaching and research sections and departments have fulfilled various teaching tasks according to the requirements, but the teaching quality and connotation construction need to be further strengthened.

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT < 150×10 9 /L) who received the DAA treatment regimen without interferon for 12-24 weeks in Tianjin Third Central Hospital from April 2018 to March 2019, and the changes in virologic response, liver function parameters, PLT, and liver stiffness measurement (LSM) were evaluated at the end of treatment (EOT) and at week 12 after EOT. Quantitative data accord with normal distribution were compared by repeated measures ANOVA. Normal transformation was performed before the comparison between skewed data, then repeated measures ANOVA was carried out. A logistic regression analysis was used to investigate the predictive factors for PLT elevation, and the receiver operating characteristic (ROC) curve was plotted to analyze the value of LSM in predicting PLT elevation after treatment. Results Among the 83 CHC patients with thrombocytopenia, 61.4% had liver cirrhosis, and the rate of sustained virologic response at week 12 after the end of treatment (SVR12) was 98.8%. From baseline to EOT and SVR12, the patients had significant reductions in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and globin, a significant increase in the serum level of albumin, and a significant reduction in LSM (all P < 0.05). For all patients, PLT at EOT and SVR12 was significantly higher than that at baseline [EOT vs baseline: (110.4±44.6)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01; SVR12 vs baseline: (109.0±47.7)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01]. At SVR12, there were significant differences in the proportion of patients with liver cirrhosis, baseline LSM, and baseline white blood cell count between the PLT elevation group and the non-PLT elevation group (all P < 0.05). The multivariate logistic regression analysis showed that LSM was an independent predictive factor for significant PLT elevation after DAA treatment (odds ratio=0.929, 95% confidence interval: 0.864-0.999, P < 0.05). Baseline LSM had an area under the ROC curve of 0.644 in predicting PLT elevation, with a sensitivity of 81.0% and a specificity of 48.6% at a cut-off value of 20.15 kPa. The patients with PLT > 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

【Objective】 Compare the early outcome and safety of endoscopy-unilateral laminectomy for bilateral decompression （Endo-ULBD） and posterior lumbar interbody fusion （PLIF） in the treatment of multi-segment lumbar central spinal stenosis. 【Methods】 We retrospectively analyzed 68 patients with multi-segment central lumbar spinal stenosis treated between October 2019 and October 2020 in the Department of Spine Surgery， Affiliated Hospital of Qingdao University. Of them 33 patients were treated with Endo-ULBD and 35 ones were treated with PLIF. We compared the operation time， times of intraoperative fluoroscopy， estimated intraoperative blood loss， incision length， postoperative time to get out of bed， postoperative hospital duration， complications， visual analogue scale （VAS）， Oswestry dysfunction index （ODI） score before and 1 day， 1 month， and 3 months after operation， Japanese Orthopedic Association Assessment Treatment Score （JOA）， and modified MacNab score 3 months after operation between the two groups of patients. 【Results】 Compared with PLIF group， Endo-ULBD group had significantly shorter operation time， smaller incision length， less intraoperative blood loss， shorter postoperative bed time and postoperative hospital stay， and fewer surgical complications （all P<0.05）. There was significantly more intraoperative fluoroscopy in Endo-ULBD group than in PLIF group （P<0.05）. The VAS， ODI and JOA scores of the two groups were significantly improved after treatment （P<0.05）. There was no statistical difference in VAS of leg pain between the two groups after treatment （P>0.05）. However， after treatment Endo-ULBD group outperformed PLIF group in lower back pain VAS， ODI， JOA and the 3-month follow-up excellent and good rates （P<0.05）. 【Conclusion】 For patients with multi-segment central lumbar spinal stenosis， Endo-ULBD treatment can achieve better early clinical outcome than PLIF surgery， with less bleeding， shorter operation time， faster postoperative recovery， and fewer complications.

Objective: To provide guidelines for the prevention of post-stroke dementia, we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge. Methods: Five dementia-related questions were designed. A field survey was conducted in a question-and-answer method using the designed questions. The surveys assessed 3000 stroke patients (2 weeks-6 months after stroke attacks) from 14 hospitals/clinical centers in 7 provinces and cities across China. Results: Among 3000 stroke patients, 80.5％had heard of dementia, 39.1％knew that stroke can lead to dementia, 55.7％ believed dementia can be prevented, 50.8％ thought dementia can be cured, and only 8.8％had ever seen a doctor because of memory deterioration. Then, patients were classified into three groups, including a no cognitive impairment (NCI) group, a mild cognitive impairment (MCI) group, and a mild dementia (MD) group. Among the MCI and MD groups, only 8.7％ (75/861) and 9.9％ (64/649) of patients, respectively, had ever seen a doctor because of memory deterioration. According to our results, patients with a higher level of cognitive impairment had a lower awareness of dementia (P<.001). Conclusion: The awareness of dementia in stroke patients in China is low, and the consultation rate is even lower. Moreover, patients with a higher level of cognitive impairment have a lower awareness of dementia. To improve public awareness and improve prevention, more emphasis should be put on ed-ucation regarding post-stroke dementia. Routine cognitive function screening should be conducted on stroke patients as an effective way to assess dementia.

Objective:To evaluate the effects of fluorinated porcine hydroxyapatite (FPHA) on guided bone regeneration of peri-implant buccal bone defects in canine mandible.Methods:Six male beagle dogs were randomly divided into two groups with different time points (4 weeks and 12 weeks after implants placement), with 3 dogs in each group. Bilateral mandibular second premolars, first molars, and second molars in each dog were extracted. The wounds were allowed to heal for 12 weeks. For each dog, four implant beds were prepared in each side and standardized peri-implant buccal bone defect was created at each implant site. After implants placement, the defect sites were randomly allocated in a split-mouth design to blank control group, deproteinized bovine bone mineral (DBBM), the porcine hydroxyapatite (PHA), FPHA and covered with collagen membranes. The animals were sacrificed 4 or 12 weeks after the surgery. Biopsies of the implant sites were obtained for micro-CT evaluation [bone volume fraction (BV/TV) and bone trabecular separation degree (Tb.Sp)] and histological analysis.Results:Micro-CT results showed that 4 weeks after implants placement, PHA, FPHA and DBBM successfully maintained the contour of alveolar ridge at the buccal aspect of the implants, while the contour of alveolar ridge collapsed in the blank control group. BV/TV in the FPHA group [(24.77±2.20) %] was significantly higher than that in the PHA group [(16.89±1.70)%] and DBBM group [(15.68±3.15)%] ( P<0.05). Tb.Sp in the FPHA group (0.70±0.07) was significantly lower than that in the DBBM group (1.03±0.19) ( P<0.05). Twelve weeks after implants placement, the alveolar ridge contour of the grafted sites in PHA, FPHA and DBBM group remained stable. The alveolar ridge of the blank control group was still collapsed. There was no significant difference in BV/TV and Tb.Sp between PHA group, FPHA group and DBBM group. The histomorphological analysis showed that 4 weeks after implants placement, in the central area of the defect, the amount and maturity of new bone (NB) around the material particles in FPHA group was higher than that in PHA group and DBBM group. Osseointegration could be observed between the NB and implant surface in all the four groups. Twelve weeks after implants placement, the material particles were surrounded by a large number of mature NB in PHA, FPHA and DBBM group. Conclusions:The incorporation of fluoride ion into PHA could effectively promote the repair of peri-implant bone defects in the early stage of guided bone regeneration.

Objective: To investigate the effect of long-term exposure of nitrogen dioxide on the incidence of hypertension. Methods: From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow-up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self-report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO₂ during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO₂ exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO₂ exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results: The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m². During an average follow-up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m³. After adjusting for age, sex, BMI, family history of hypertension, socio-economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m³ increase of NO₂ was 1.21 (95%CI: 1.18-1.25). Compared with residents aged 60 years and over (HR=1.19, 95%CI: 1.14-1.26), former and current smoking (HR=1.20, 95%CI: 1.14-1.25), and high-frequency fruit consumption (HR=1.17, 95%CI: 1.13-1.21), residents younger than 60 years (HR=1.28, 95%CI: 1.25-1.32), non-smoker (HR=1.23, 95%CI: 1.19-1.27), and low-frequency fruit consumption (HR=1.27, 95%CI: 1.20-1.35) had stronger interaction effect with NO₂ (all P values for interaction<0.05). Conclusion NO₂ exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low-frequency fruit consumption.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.