Dystrophinopathies caused by variants of DMD gene are a group of muscular diseases including Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy. With the advancement of genetic testing techniques and wider implementation of genetic screening, especially the expanded carrier screening, more and more individuals carrying DMD gene variants have been identified, whereas the genetic counseling capacity is relatively insufficient. Currently there is still a lack of professional norms for genetic counseling on dystrophinopathies. In this consensus, the main points to be covered in the pre- and post-test consultation have been discussed, with an aim to provide genetic counseling guidance for the disease diagnosis, treatment, and family reproduction.

Aim To investigate the effect of alfentanil on myocardial ischemia-reperfusion injury(MIRI)in rats and its regulatory mechanism on the sphingosine kinase 1(SphK1)/sphingosine-1-phosphate(S1P)signaling pathway dur-ing this process.Methods SPF grade SD male rats were randomly divided into sham surgery group,model group,positive drug group(compound salvia miltiorrhiza group),low dose alfentanil group,high dose alfentanil group,and high alfentanil+SphK1 agonist group(alfentanil+PMA group),with 20 rats in each group.Except the sham operation group,the MIRI model was reproduced by ligating the left anterior descending coronary artery and reperfusion.The activities of serum lactate dehydrogenase(LDH),creatine kinase(CK)and aspartate aminotransferase(AST)were detected by auto-matic biochemical analyzer;TTC was applied to detect the size of myocardial infarction in rats;HE staining was applied to observe the morphological characteristics of rat myocardial tissue;TUNEL staining was applied to detect myocardial cell ap-optosis in rats;ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),inter-leukin-1β(IL-1β),and S1P;kits were applied to detect content of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in myocardial tissue;Western blot was applied to detect the expression level of SphK1 protein in myocar-dial tissue.Results Compared with the sham surgery group,the pathological damage to the myocardial tissue of rats was severe in the model group,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial in-farction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all increased,the activity of SOD decreased(P＜0.05).Compared with the model group,the myocardial tissue damage of rats was reduced in the positive drug group and the low and high dose alfentanil groups,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial infarction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all decreased,the activity of SOD increased(P＜0.05).The SphK1 agonist was able to reverse the impact of high-dose alfentanil on the above indicators(P＜0.05).Conclusion Alfentanil has protective effect on MIRI rats,and its mechanism may be related to the inhibition of SphK1/S1P signaling pathway.

Objective:To examine the association between macrophage migration inhibitory factor(MIF), Interleukin 6(IL-6), periodontal disease, and atherosclerosis in middle-aged and elderly individuals.Methods:This cross-sectional study enrolled 700 diabetic patients who were attending the endocrinology department of Beijing Hospital from January 2020 to December 2022.Out of these patients, 491 underwent a full-mouth periodontal examination.Among them, 106 were middle-aged and elderly.The study included 83 patients with complete data, aged between 45 and 70 years(mean age: 58.2±8.7 years).Among the included patients, 48 were male(57.8%)and 35 were female(42.2%).A questionnaire was administered to gather information about the patients, and serum levels of MIF and IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).The relationship between serum MIF and IL-6 levels and periodontitis and atherosclerosis was evaluated through univariate and multifactorial analyses conducted on middle-aged and elderly individuals.Results:There were 66 cases(79.5%)in the periodontitis stage Ⅰ/Ⅱ group and 17 cases(20.5%)in the stage Ⅲ/Ⅳ group.The serum MIF levels in the two groups were(2, 312.5±795.0)ng/L and(2, 939.8±665.0)ng/L, respectively( P<0.01).Similarly, IL-6 levels were(3.5±3.0)ng/L and(6.7±6.1)ng/L in the two groups( P>0.05).The findings revealed that for each 1 ng/L increase in MIF serum levels, the risk of severe periodontitis and increased carotid intima-media thickness(cIMT)increased by 0.1%.Furthermore, for each 1 ng/L increase in serum MIF and IL-6 levels, the risk increased by 0.2% and 38.9% respectively.Serum MIF levels were found to be associated with atherosclerosis as well as with various factors related to periodontitis, including periodontal probing depth, bleeding index, clinical attachment level, periodontal probing depth≥4 mm sites, clinical attachment level≥5%, and bleeding index >2%(all P<0.05). Conclusions:This study investigates the correlation between MIF and IL-6 levels with Periodontal disease and Atherosclerosis in middle-aged and elderly individuals.

Objective:To study the clinical significance of plasma D-dimer for extended anticoagulation in the elderly patients with hip fracture after discharge.Methods:The data were retrospectively analyzed of the 355 elderly patients with hip fracture who had been admitted to Emergence Center of Trauma and Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University from January 2016 to November 2020. There were 107 males and 248 females with a mean age of 79.0 years (from 65 to 102 years). There were 179 femoral neck fractures, 159 intertrochanteric fractures, and 17 subtrochanteric fractures. Plasma D-dimer concentrations were detected at admission, before surgery, and 35 days after surgery. Color Doppler ultrasonography of deep veins of lower extremities was performed at admission, before surgery, before discharge, and 35 days after surgery. The patients with deep vein thrombosis (DVT) at the time of discharge should were reexamined 15 days after discharge. Strategies for anticoagulation prevention and treatment were formulated according to the patients' plasma D-dimer, color Doppler ultrasonography results, symptoms and signs. Plasma D-dimer concentrations were compared between patients with thrombosis and without thrombosis at different time points.Results:The plasma D-dimer concentrations for the 355 patients at admission, before surgery and 35 days after surgery were 2.73 (1.72, 5.13) mg/L, 1.31 (0.72, 2.58) mg/L, and 0.49 (0.25, 0.80) mg/L, respectively. The level of D-dimer at 35 days after surgery was significantly lower than that at admission and before surgery ( P<0.05). There were, respectively, 105, 126,191 and 148 patients with DVT at admission, before surgery, before discharge and 35 days after surgery, and the DVT was distal in most cases. The D-dimer concentrations for patients with thrombosis and without thrombosis at 35 days after surgery was 0.64 (0.32, 1.00) mg/L and 0.37 (0.22, 0.68) mg/L respectively, showing a significant difference ( P<0.05). The area under the receiver operating characteristic curve of plasma D-dimer for the diagnosis of DVT at 35 days after surgery was 0.665. Conclusions:Extended anticoagulation and continuous monitoring of plasma D-dimer are very important for elderly patients with hip fracture after discharge. For patients with DVT at discharge, negative plasma D-dimer is a sign for termination of anticoagulation; for patients without DVT at discharge, it is reasonable to extend anticoagulation 35 days after surgery.

Objective: To investigate the influence of mechanical debridement on the subgingival microbiome in chronic periodontitis by 16S rRNA high-throughput sequencing. Methods: Patients with generalized moderate to severe chronic periodontitis were recruited into this study and received oral hygiene instruction and supragingival scaling. One week later, they received ultrasonic and manual subgingival scaling and root planning. Clinical parameters were recorded and subgingival plaques were sampled at baseline and 3 months and 6 months after treatment. The comprehensive profiles of the subgingival microbiome were analyzed by sequencing the V3-4 region of 16S rRNA with the Illumina MiSeq platform. Results : Alpha diversity analysis showed that the richness and diversity of the subgingival community were consistent before and after treatment, but a significant difference in community structure was detected only between baseline and month 3 by principal coordinates analysis (PCoA). After 3 months, the clinical parameter as probing depth (PD) decreased significantly and the relative abundances of the genera related to periodontitis such as Porphyromonas, Treponema, Tannerella, and Filifactor decreased significantly. Meanwhile, the relative abundances of the genera associated with periodontal health increased, such as Capnocytophaga, Kingella. Six months later, however, less genera related to periodontitis decreased significantly from the baseline level, such as Filifactor. PD decreased significantly compared with baseline, but increased significantly compared with 3 months after treatment. Conclusion Mechanical debridement alone could relieve periodontal inflammation and balance microbial dysbiosis and the greater efficacy occurred 3 months after treatment.

Objective:To investigate the correlation between clinical periodontal indexes of periodontitis and glomerular filtration rate (GFR) in a non-diabetic elderly population in four communities of Shijingshan, Beijing.Methods:This was a cross-sectional study. Questionnaires, blood biochemical examinations, and periodontal indexes were conducted in elderly people (35 to 84 years old) in four communities of Shijingshan, Beijing between May and July 2005. Non-diabetic patients with fasting blood glucose<6.1 mmol/L, postprandial blood glucose<7.8 mmol/L, and ≥ 10 remaining teeth were included. Patients with diabetes, fasting blood glucose ≥6.1 mmol/L or postprandial blood glucose ≥7.8 mmol/L, and total residual teeth less than 10 were excluded. A total of 362 study subjects met the inclusion criteria. The survey subjects were selected by convenient sampling method. The mean full-mouth probing depth (PD), bleeding index (BI), attachment loss (AL), and plaque index (PLI), as well as PD≥4 mm% (the number of sites with PD≥4 mm as a percentage of the total number of sites in full mouth), PD≥5 mm%, PD≥6 mm%, AL≥3 mm%, AL≥4 mm%, AL≥5 mm% and AL≥6 mm% were used for the analysis. Serum creatinine values was used to calculate GFR. GFR≥90 ml/(min·1.73 m 2) was defined as normal group and GFR<90 ml/(min·1.73 m 2) was defined as reduced group. Univariate analysis was conducted between two groups. Multivariate regression analysis was performed with GFR as dependent variable and adjusted for risk factors such as age, sex, smoking, waist-hip ratio and physical activity. Results:There were 164 subjects in the normal GFR group (45.3%) and 198 in the reduced GFR group (54.7%). Percentage of males in the reduced GFR group, 118 in total, accounting for 59.6%, were significantly higher than in the normal GFR group (73, 44.5%)( P=0.004). The median of age, uric acid, triglyceride, and waist-to-hip ratio (65 years, 323 mmol/L, 1.73 mmol/L, 0.90) were significantly higher in the reduced GFR group than in the normal GFR group (54 years, 277 mmol/L, 1.45 mmol/L, 0.88) ( P<0.05). The median of PD mean, AL mean, BI mean, PD≥4 mm%, AL≥3 mm%, and AL≥4 mm% in the reduced GFR group were 2.80 mm, 2.52 mm, 2.06, 20.4%, 46.5%, and 30.4%, respectively, which were significantly higher than those in the GFR normal group (2.60 mm, 2.37 mm, 1.93, 16.6%, 42.9%, 28.9%) ( P<0.05). After adjusting for confounding factors such as age, gender, smoking, waist-to-hip ratio and physical activity, the results of logistic regression analysis showed that PD mean, AL mean, PD≥4 mm%, PD≥5 mm%, PD≥6 mm%, AL≥3 mm% and AL≥4 mm% of clinical periodontal indexes were significantly correlated with reduced GFR in this population ( OR values were 1.765, 1.879, 1.430, 1.713, 1.771, 1.428, 1.445, respectively, P<0.05). Conclusions:In the non-diabetic elderly population in communities of Shijingshan, Beijing, clinical periodontal indexes reflecting the degree of periodontal tissue destruction were associated with a decreased level of GFR.

Objective:To investigate the status quo of human resources of dentists who deal with periodontal disease in Beijing area through an online survey, which may hopefully provide a preliminary basis for the decision-making of administrative departments and the formulation of periodontal professional development plan.Methods:The dentists who deal with periodontal disease at least half a day per week in Beijing area were investigated. A questionnaire was designed by the chairman of the Periodontology Committee of Beijing Stomatological Association. The questionnaire was sent to and finished by the dentists via "WenJuanXing" online survey software. The contents of the survey included general condition, the property of practice unit, title and position of the dentist, membership of professional society, time and content of periodontal treatment, adoption of new technology and new method of periodontal therapy during the past one year, status of periodontal treatment in the local population and reasons, understanding and influencing factors of periodontal professional development.Results:A total of 1 255 dentists completed the survey, who came from all 16 districts in Beijing, mainly Haidian, Chaoyang, Dongcheng and Xicheng Districts [The total percentage of these four main districts was 70.3% (882/1 255)]. The mean age of the dentists was (36.1±8.3) years. Among the dentists, 71.1% (892/1 255) were females, 88.1% (1 106/1 255) got a Bachelor′s degree or above. It was estimated that 35.4% (444/1 255) of the dentists had received standardized periodontal training ever. The percentage of dentists carrying out new technology in the past one year was as high as 68.1% (855/1 255). There were only 163 periodontal specialists (13.0%) out of the dentists in the survey. Only 15.9% (200/1 255) of the dentists routinely performed periodontal surgery. The majority of the dentists [82.8% (1 039/1 255)] were from the state-owned hospitals. Fifty-four point seven percemt (686/1 255) of the dentists thought that lack of knowledge was the main reason why the general public failed to receive periodontal treatment. As for the biggest bottleneck affecting periodontal professional development, fifty-one point zero percent (640/1 255) of the dentists attributed it to the public neglect.Conclusions:The periodontal practitioners in Beijing are young, highly educated, unevenly distributed in 16 districts and mostly females. State-owned oral health institutions are an important force in periodontal diagnosis and treatment services in Beijing. The number of periodontal specialists need to be improved. Promotion of standardized periodontal surgery and the popularization of healthcare knowledge on periodontal disease should also be the focus in the future.

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNF (CHX/TNF)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

Objective To investigate the clinical features and antimicrobial susceptibility of neonatal Listeria septicemia.Methods Eleven cases of neonatal Listeria septicemia that were treated in the Huzhou Maternity and Children Health Hospital from March 2013 to March 2017 were enrolled in this study.Clinical data including the results of bacterial culture,antimicrobial susceptibility test and antibiotic treatment were collected and retrospectively analyzed.Moreover,maternal history of Listeria monocytogenes (LM) infection before delivery was retrieved.Results All of the 11 mothers had fever before delivery and nine of them showed different grades of amniotic fluid contamination during delivery.Clinical symptoms of the 11 neonates included dyspnea (11 cases),fever (ten cases),apnea (nine cases),slow response and feeding difficulty (nine cases),convulsion (six cases),vomiting and abdominal distension (two cases),pulmonary hemorrhage (one case),progressive jaundice (one case) and systemic skin bleeding point (one case).All cases showed abnormal results of blood routine test and increased calcitonin and C-reactive protein.Ten cases received cercbrospinal fluid examination,seven of which were abnormal.Altogether 17 strains of LM were isolated from various specimens.These strains were all sensitive to piperacillin-tazobactam,ampicillin-sulbactam,meropenem,vancomycin,cotrimoxazole,ciprofloxacin and gentamycin,but resistant to oxacillin.Strains those were sensitive to penicillin,ampicillin,erythromycin and clindamycin accounted for 10/17,11/17,9/17 and 8/17,respectively.The 11 neonates were treated with piperacillin-tazobactam,meropenem or vancomycin.All of them improved (11/11)and ten were cured (10/11).All cases were followed up through phone calls at one week and one month after discharge.Two were lost to follow-up,while thc others were all in good condition.Conclusions Neonatal Listeria septicemia is usually a severe disease characterized by rapid progression and mainly presented with dyspnea and fever,besides there is a high possibility of purulent meningitis.Some LM strains are resistant to single-agent penicillin antibiotics.However,antibiotics such as piperacillin-tazobactam,meropenem and vancomycin are effective in the treatment of neonatal Listeria septicemia.