Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

The changes in epigenetic modifications of histones are one of the important factors in cancer development and metastasis,and the development of epigenetic therapies for cancer treatment has led to epigenetic drug screening as a research focus. In this work,the common methylation and acetylation modifications at the N-terminal of cellular histones H3 were quantified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,and a throughput assay for screening and assessment of epigenetic drug was established. A total of 39 kinds of modification combinations containing common methylation and acetylation sites of H3 peptides were simultaneously monitored by triple quadrupole mass spectrometry in multiple reaction monitoring (MRM) mode. The developed method was applied to analyze HepG2 cells exposed for 24 h to 28 kinds of epigenetic drugs that could modulate the level of methylation or acetylation modifications. Results showed that 25 of these drugs,such as deacetylase inhibitors Abexinostat,Valproic acid and AGK7,induced histone H3 modification changes in the exposed cells that were consistent with those reported in the literature,while other modification changes were also detectable. Three of these drugs,including demethylase inhibitors IOX1,GSK-j1 and acetyltransferase inhibitor L002,however,induced modification changes different from those reported in the literature. An overall test match rate of 89.3％ was achieved. The established LC-MS/MS method could quantitatively analyze histone H3 modification sites and their changes in cells in a high-throughput and highly sensitive manner,and could be applied to the evaluation of epigenetic drugs with known activities,with good specificity and rich modification information,which was expected to provide a new technological tool for screening and evaluation of epigenetically active compounds and exploration of their mechanism of action.

Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective To observe the value of semi-quantitative parameters related to gated myocardial perfusion imaging(G-MPI)for predicting occurrence of major adverse cardiovascular events(MACE)in patients with chronic kidney disease(CKD).Methods Totally 148 CKD patients who underwent rest G-MPI(R-GMPI)(R-GMPI group,n=95)or stress/rest G-MPI(S/R-GMPI)(S/R-GMPI group,n=53)were retrospectively included.The patients were categorized into MACE subgroup and non-MACE subgroup according to MACE occurred or not during follow-up.Clinical data and G-MPI parameters were compared between subgroups,and independent predictors of MACE in CKD patients were obtained using multivariate Cox proportional hazards regression analysis.Receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated to assess the efficacy of each independent predictor for predicting MACE.Among patients who underwent only R-GMPI,the optimal cut-off value of each parameter for predicting MACE was obtained by ROC curve analysis,and the risk of MACE was stratified,then Kaplan-Meier curves were drawn and compared with log-rank test.Results Among 95 patients who underwent only R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had smaller body mass index(BMI)and higher proportion of previous myocardial infarction and hemodialysis,as well as higher R-GMPI left ventricle end-diastolic volume(R-LVEDV),left ventricle end-systolic volume(R-LVESV),sum rest score(R-SRS)but lower left ventricle ejection fraction(R-LVEF)(all P＜0.05),while R-SRS(HR=1.068,95％CI[1.027,1.110])and R-LVESV(HR=1.011,95％CI[1.005,1.017])were both independent predictors for MACE(both P＜0.05).Among 53 patients who underwent S/R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had with higher blood creatinine and lower estimated glomerular filtration rate(eGFR),higher S-LVESV,R-LVEDV,sum stress score(SSS),SRS and sum difference score(SDS)(all P＜0.05),and SDS(HR=1.454,95％CI[1.063,1.989])was an independent predictor for MACE(P＜0.05).Among 95 CKD patients who underwent only R-GMPI,AUC of R-SRS and R-LVESV alone for predicting MACE was 0.659 and 0.694,respectively,and higher incidence of MACE was found in those w ith R-SRS ≥8 points,also in those with R-LVESV ≥91 ml(both P＜0.05).Conclusion G-MPI could be used to evaluate myocardial perfusion and function in CKD patients.For CKD patients just underwent only R-GMPI,R-SRS and R-LVESV were independent predictors for MACE,whereas SDS might be utilized to predict MACE in CKD patients who could undergo S/R-GMPI.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To establish the normal reference value of left ventricular function parameters by cadmium-zinc-tellurium (CZT) SPECT stress gated myocardial perfusion imaging (G-MPI) in low-likelihood of stable coronary artery disease (SCAD).Methods:From March 2022 to August 2022, 348 consecutive SCAD patients (146 males, 202 females, age (58±10) years) who underwent exercise or pharmacological stress G-MPI (CZT SPECT) in Beijing Anzhen Hospital, Capital Medical University were retrospectively recruited. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were acquired using quantitative gated SPECT (QGS) analysis. EDV and ESV were corrected by body surface area (BSA) to obtain EDV index (EDVI) and ESV index (ESVI), respectively. Independent-sample t test, one-way analysis of variance and Mann-Whitney U test were used for data analysis. The influences of EDV, ESV, EDVI, ESVI and LVEF were analyzed by multiple regressions for linear models. Results:There were 314 patients with low-likelihood of SCAD (128 males, 186 females, age (58±10) years) and 34 normal controls (18 males, 16 females, age (55±10) years). There were no significant differences of basic clinical characteristics and left ventricular function parameters in different genders between 2 groups ( z values: from -1.74 to -0.02, t values: from -1.16 to 1.17, all P>0.05). Using the 95% CI as the cut-off value for left ventricular function parameters in patients with a low-likelihood of SCAD, the upper limits of EDV, ESV, EDVI and ESVI in females and males were 84 and 111 ml, 30 and 44 ml, 47 and 54 ml/m 2, 17 and 21 ml/m 2, respectively, and the lower limit of LVEF in females and males were 58% and 55%, respectively. In the low-likelihood of SCAD group, the EDV ((58±13) vs (77±17) ml) and ESV ((16±7) vs (26±9) ml) of females were smaller than those of males ( t values: 10.65, 10.35, both P<0.001), while LVEF of females was higher than that of males ((72±7)% vs (67±6)%; t=-6.23, P<0.001). However, there were no significant differences in left ventricular function parameters among different age groups with the same gender ( F values: 0.12-2.19, all P>0.05). Based on multiple regression for linear models, the primary predictors of EDV, ESV and LVEF were gender and weight ( β values: from -0.380 to 0.358, all P<0.05). Conclusions:Normal reference values of left ventricular function parameters are established by CZT SPECT stress G-MPI in low-likelihood of SCAD patients. Left ventricular EDV and ESV of females are smaller than those of males, while LVEF of females is higher than that of males. The influence of gender on left ventricular function parameters should be considered in clinical practice.