Objective: To investigate the relationship between 24-hour ambulatory pulse pressure (24hPP), 24-hour ambulatory pulse pressure index (24hPPI), night-time ambulatory pulse pressure index (NPPI) and coronary artery disease (CAD) occurrence in hypertension patients. Methods: A total of 305 subjects received ambulatory blood pressure monitoring (ABPM) in our hospital from 2016-05 to 2016-07 were enrolled. Base on ABPM information, 24hPP, 24hPPI and NPPI were calculated to analyze their relationship to CAD occurrence. 24hPP was defined by 24-hour mean systolic blood pressure (24hSBP) minus 24hDBP, 24hPPI by the ratio of 24hPP/24hSBP and NPPI by the ratio of night (22:00-6:00) PP/SBP. Results: There were 222/305 (72.8%) subjects with hypertension. Compared with normotension subjects, hypertension patients had increased 24hPP: (49.0±11.6) mmHg vs (42.2±7.4) mmHg, P<0.001, 24hPPI: (0.39±0.06) vs (0.37±0.05), P=0.004 and NPPI: (0.40±0.07) vs. (0.38±0.06), P=0.009 respectively. 116/222 (52.3%) hypertension patients suffered from CAD. Compared with non-CAD patients, CAD patients presented elevated 24hPP: (50.9±12.2) mmHg vs (47.0±10.6) mmHg, P=0.013, 24hPPI: (0.41±0.07) vs. (0.38±0.06), P<0.001 and NPPI: (0.42±0.07) vs. (0.38±0.06), P<0.001 respectively. Among 83/305 (27.2%) normotension subjects, the above indexes were similar between CAD patients and non-CAD subjects. Logistic regression analysis demonstrated that with adjusted age, gender, body mass index (BMI) and antihypertensive medication, 24hPPI [OR=1.95, 95% CI 1.11-3.44, P=0.020] and NPPI [OR=2.21, 95% CI 1.28-3.82, P<0.01] were related to CAD occurrence. ROC curve analysis showed that 24hPPI and NPPI were superior to 24hPP for CAD screening and prediction in hypertension patients. Conclusion: 24hPPI and NPPI were closely related to CAD occurrence in hypertension patients, they were both helpful for CAD screening and prediction in hypertension patients.

Objective: To investigate the relationship between blood pressure variability and ambulatory arterial stiffness index (AASI) in both normal subjects and hypertensive patients.
Methods: A total of 280 consecutive subjects without antihypertensive medication were studied. All subjects received ambulatory blood pressure monitoring (ABPM) and AASI was calculated as 1 minus the regression slope of diastolic blood pressure value vs systolic blood pressure value according to ABPM recording.
Results: ① There were 161 subjects with male gender, 138 patients with hypertension, and the average age was (50.4 ± 13.3) years.②Pearson analysis indicated that AASI was related to age (r=0.272, P<0.001), 24-hour mean pulse pressure (r=0.504, P<0.001) , nocturnal diastolic blood pressure dipping (r=-0.334, P<0.001) and standard deviation of 24-hour diastolic blood pressure (r=-0.520, P<0.001).③AASI in anti-dipper hypertensive patients was higher than that in dipper patients, P<0.05;while AASI between dipper and non-dipper patients, dipper and extreme-dipper patients were similar, P>0.05 respectively.④Multiple linear regression analysis demonstrated that with adjusted age, gender, BMI and blood pressure, AASI was independently related to 24-hour mean pulse pressure (β=0.003, P<0.001), nocturnal diastolic blood pressure dipping (β=-0.001, P<0.05), standard deviations of 24-hour systolic blood pressure (β=0.032, P<0.001) and 24-hour diastolic blood pressure (β=-0.064, P<0.001), standard deviation of 24-hour heart rate (β=0.006, P<0.001).
Conclusion:AASI is closely related to blood pressure variability, it’s a comprehensive index for arterial stiffness and blood pressure variability.

Objective To investigate the effect of shenfu injection on immune function in severe trauma patients.Methods 60 severe trauma patients were divided into the control group (n =30)and shefu group (n =30) by random number table.Other 30 cases were chosen as the health control group at the same phase.All patients were received conventional treatments,however,patients of the shenfu group were additionally received the shenfu injection treatment in the early stage.The CD +3 ,CD +4 ,CD +8 cell,human leukocyte antigen (HLA -DR),interleukin -1(IL -1),interleukin -6(IL -6)were detected on 3rd and 7th day by double -antibody sandwich enzyme -linked immu-nosorbent assay (ELISA).Results Compared to the health control group,the IL -1,IL -6 in the control and shenfu group were significantly higher than the health control group(f=7.128,q =9.212,10.112,all P <0.05).The IL -1and IL -6 in the control and shenfu group were significantly increased on 3rd day (t =11.126,10.013,all P <0.05)and decreased on 7th day(t =17.121,14.213,all P <0.05).The IL -1 and IL -6 in shenfu group were sig-nificantly lower than that of the control group(χ2 =4.113,10.117,all P <0.05).The CD +3 ,CD +4 ,CD +8 ,HLA -DR and CD +3 /CD +8 rate in the control and shenfu group were significantly lower than the health control group(f=11.071, q =10.229,12.032,all P <0.05).On 3rd day,the CD +3 ,CD +4 ,CD +8 ,HLA -DR and CD +3 /CD +8 rate in shenfu group were significantly increased(t =10.013,P <0.05).On 7th day,CD +3 ,CD +4 ,CD +8 ,HLA -DR and CD +3 /CD +8 rate in the control and shenfu group were both increased(t =11.126,15.932,all P <0.05).And the CD +3 ,CD +4 ,CD +8 ,HLA -DR and CD +3 /CD +8 rate in shenfu group were significantly higher than the control group(χ2 =3.771,P <0.05).Conclusion Shenfu injection can regulate immune function in severe trauma and improve clinical treatment.

In addition to hearing impairment, syndromic hearing impairment is often accompanied by disorders of urinary, skeletal, muscular, nervous, and ocular systems. Genetic factors have shown to play an important role in the pathogenesis of deafness. Mutations of X-linked genes may cause syndromic hearing impairment. Gene mapping, linkage analysis and next-generation sequencing may facilitate delineation of the pathogenesis of X-linked syndromic hearing impairment. This article reviews recent progress in molecular genetic research on X-linked syndromic hearing impairment, which may shed light for the diagnosis and treatment of these diseases.
Genetic Diseases, X-Linked ; genetics ; Genetic Research ; Hearing Loss ; diagnosis ; genetics ; therapy ; Humans ; Molecular Biology

OBJECTIVE: To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG). METHODS: For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene. RESULTS: Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis. CONCLUSION Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.
Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.

Objective To investigate the medical cost and clinical efficacy of the new quadruple regimen with sodium-glucose linked transporter 2(SGLT2)inhibitor in treatment of heart failure(HF),and to provide economic reference for choosing treatment drugs for HF patients.Methods A total of 86 HF patients hospitalized in Ningbo Medical Center Lihuili Hospital from January 2022 to January 2023 were retrospectively selected as study objects.According to actual HF treatment regimen,the patients were divided into experimental group and control group,43 cases in each group.The experimental group received the new quadruple therapy regimen,and the control group received classical therapy regimen.Clinical efficacy,cardiovascular events and direct medical costs within 1 year were compared between two groups.Incremental cost-effectiveness ratio(iCER)was calculated,and sensitivity analysis was performed on the results.Results The direct medical costs of patients in experimental group were slightly higher than those in control group,but there was no statistically significant difference between two groups(￥12513.0 vs.￥11508.9,t=-0.079,P=0.125).There was no significant difference in total effective rate between experimental group and control group(81.40％vs.74.4％,x2=1.237,P=0.539).There was no significant difference in cardiovascular events within 1 year between two groups(x2=0.073,P=0.787).The cost-effectiveness ratio(C/E)of experimental group and control group were 15372.3 and 15468.9,respectively,and iCER was 143.5.Sensitivity analysis showed that the results were robust.Conclusion The clinical efficacy of control group and experimental group for HF was similar,but the C/E of experimental group was slightly higher than that of control group,and the new quadruple regimen with SGLT2 inhibitors had more pharmacoeconomic advantages.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Clinical phenotypes and gene characteristics of a patient diagnosed with Mowat-Wilson syndrome (MWS) with Hirschsprung′s disease (HSCR) and vaginal atresia in the Department of Neonatal Surgery, Beijing Children′s Hospital, Capital Medical University in March 2021 were analyzed retrospectively.The eight-month-old girl was admitted to the hospital with symptoms of constipation for nine days and abdominal distension for two days.Lower digestive tract radiography and rectal mucosa biopsy results suggested HSCR.The child also had specific facial features and motor development delay.Whole exome test showed a de novo heterozygous mutation, ZEB2 gene c. 2761C>T (p.R921*). After laparoscopic-assisted Soave procedure, the child had normal bowel movements, and no surgery-related compli-cations occurred during the follow-up period.The child′s motor development improved after rehabilitation treatment.According to literature review, 2 female cases show similar clinical manifestations to this girl, but the genotypes were different.This patient expands the clinical phenotype of ZEB2 gene pathogenicity.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.