Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To verify the accuracy of a Non-Contact Sleep Monitoring Mattress(NCSMM)based on body movement during sleep in assessing sleep quality of patients before neurosurgery in order to provide a more portable and efficient assessment tool for clinical staff.Methods A single-arm trial was conducted on 114 inpatients admitted in our department selected with convenience sampling.Sleep quality data of 1 night were collected through 5 sleep quality assessment tools,including NCSMM,polysomnography(PSG),Patient-Reported Outcome Measurement Information System(PROMIS)Sleep Disturbance scale,Richards-Campbell Sleep Scale(RCSQ),and a wearable device(smart watch for body movements and sleep quality monitoring).The sleep efficiency(≤85%)obtained by PSG was used as the diagnostic standard for sleep disorders.The area under the receiver operating characteristic curve(AUC),sensitivity,specificity,positive predictive value,negative predictive value,and Youden index were calculated for the other 4 tools to evaluate and compare their diagnostic effectiveness.Results The AUC value for NCSMM,PROMIS,RCSQ and smart watch was 0.788(95%CI:0.687～0.888,P<0.001),0.664(95%CI:0.543～0.784,P=0.02),0.723(95%CI:0.600～0.846,P=0.001)and 0.750(95%CI:0.654～0.846,P<0.001),respectively.The diagnostic accuracy rate was 0.774,0.559,0.742 and 0.602,with corresponding Youden index value of 0.488,0.321,0.456,and 0.459.NCSMM demonstrated the best AUC value,sensitivity and Youden index when compared with the other 3 tools.Conclusion NCSMM shows high accuracy in assessing sleep quality in pre-neurosurgery inpatients,and it is a viable portable and efficient assessment tool in clinical practice.

Objective Under the guidance of meridian-sinew(jingjin)theory,the correlation between foot-yangming jingjin lesions and X-ray imaging findings such as medial space and lateral space in femorotibial joint and their ratio,degree of subluxation of femorotibial joint,and the Insll-Salvati index in the patients with knee osteoarthritis(KOA).Methods From January 2019 to November 2021,a total of 66 patients diagnosed as KOA at the Third Affiliated Hospital of Guangzhou University of Chinese Medicine were selected as the study subjects.The patients were divided into the foot-yangming jingjin group and non-foot-yangming jingjin group according to the presence of foot-yangming jingjin lesions.The X-ray postero-anterior and lateral radiography of the knee joint under weight bearing was performed,and imaging parameters of the two groups were measured.Afterwards the pain Visual Analogue Scale(VAS)scores and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores in the two groups were evaluated,the differences between the two groups'X-ray imaging findings and scale scores were compared,and the various X-ray imaging findings in the two groups were analyzed.Results(1)Under X-ray postero-anterior radiography of the knee joint,the medial space and lateral space in femorotibial joint and their ratio in non-foot-yangming jingjin group were lower than those in foot-yangming jingjin group,and degree of subluxation of femoro-tibial joint was higher than that of foot-yangming jingjin group(P<0.05 or P<0.01).(2)The ratio of length of patellar tendon to length of patella(LT:LP)under X-ray lateral radiography in foot-yangming jingjin group was significantly greater than that of the non-foot-yangming jingjin group(P<0.01).(3)The scores of pain VAS and WOMAC in non-foot-yangming jingjin group were both significantly higher than those in foot-yangming jingjin group(P<0.05),while the differences of the scores of WOMAC items such as joint stiffness and physiologic function,and the total WOMAC scores between the two groups were not statistically significant(P>0.05).Conclusion Foot-yangming jingjin lesions in KOA may be closely related to the relatively high position of patella under X-ray lateral radiography,and non-foot-yangming jingjin lesions may be closely related to the narrowing of the medial femorotibial joint space,the increase of medial-lateral space ratio,and the severity of subluxation under X-ray postero-anterior radiography.

Objective To explore potential association between sedentary time and the risk of all-cause mortality and cardiovascular disease(CVD)in Chinese population using data from the Prospective Urban Rural Epidemiology(PURE-China)cohort study.Methods Baseline data were collected,from 2022 standardized questionnaires and physical examinations,with follow-up until August 31,2022.The primary endpoints were all-cause mortality and cardiovascular events(non-fatal myocardial infarction,stroke or heart failure).Multivariable Cox shared frailty model was used to analyze the association between sedentary time and the risks of all-cause mortality and CVD in the target population,and to compare differences across subgroups based on gender,age and geographic location.Results A total of 47 931 participants were recruited,and 43 367 were included in the final analysis.Over a me-dian follow-up of 11.9±3.0 years,2 277 participants experienced all-cause mortality,3 551 experienced cardiovas-cular events.The Cox model indicated that,compared to individuals with less than 4 h of sedentary time per day,those with 6-8 h had a 23％increased in risk of all-cause mortality(HR=1.23,95％CI:1.06-1.44)and an 18％increased risk of CVD(HR=1.18,95％CI:1.04-1.33).For individuals with more than 8 h of sedentary time,the risk increased by 50％for all-cause mortality(HR=1.50,95％CI:1.16-1.94)and 44％for CVD(HR=1.44,95％CI:1.16-1.79).These associations were more pronounced in men and individuals aged 50 years and older.Conclusions Sedentary behavior is associated with an increased risk of all-cause mortality and cardiovascular disease in Chinese population,especially in the population with sedentary time of 6 hrs or more per day.Reducing sedentary time and increasing physical activity is an important strategy to mitigate the disease burden of cardiovascular disease and premature death.

Objective To explore the risk signals of niraparib and provide references for rational and safe clinical medication.Methods Niraparib-related adverse drug events(ADEs)reports from Q1 2017 to Q2 2023 were extracted from the US FDA Adverse Event Reporting System(FAERS)database.Risk signals were identified using the reporting odds ratio(ROR),proportional reporting ratio(PRR),Bayesian confidence propagation neural network(BCPNN),and multi-item gamma Poisson shrinker(MGPS)methods.The Risk signals were described and classified by preferred system organ classes(SOCs)and preferred terms(PTs)from the Medical Dictionary for Regulatory Activities(MedDRA)version 26.1,and the occurrence of niraparib-related ADEs was also analyzed.Results A total of 16,961 ADE reports with niraparib as the primary suspected drug were extracted.Through screening and analysis,32 PTs were identified involving 11 SOCs,which were largely consistent with the information in the drug label.However,suspicious signals not mentioned in the label,including neuropathy peripheral,decreased red blood cell count,reduced hematocrit,dehydration,and hot flashes,require further attention.The median occurrence time was 22 days(IQR 2-98 days),and the Weibull distribution test indicated an early failure-type curve.Conclusion When using niraparib,particularly in early stages of treatment,it is essential to monitor not only the ADEs mentioned in the drug instructions,such as decreased platelet count,nausea and fatigue,but also to pay close attention to the ADEs not included in the instructions,such as peripheral neuropathy and decreased red blood cell count,which exhibit strong signal values,to ensure patient medication safety.

Objective:To explore the effect of acute exercise on the executive function in patients with atten-tion deficit hyperactivity disorder(ADHD),and to provide a theoretical basis for the exercise intervention of ADHD.Methods:Experimental studies on the effect of acute exercise on executive function in patients with ADHD published up to 21 April 2023 were searched from PubMed,Web of Science,Cochrane Library,Embase,CNKI,Wanfang,and other data platforms.Results:A total of 15 studies were included,and 515 patients with ADHD were included.The results of meta-analysis showed that a single exercise could improve inhibitory control(SMD=0.36,95％CI=0.17-0.55,P＜0.05)and cognitive flexibility(SMD=0.40,95％CI=0.10-0.69,P＜0.05)in pa-tients with ADHD.The results of subgroup analysis showed that in terms of the age of the participants,a single ex-ercise could only improve inhibitory control and cognitive flexibility in children and adolescents with ADHD(SMD=0.36,0.43,Ps＜0.05),but not in adult patients with ADHD(SMD=0.34,0.14,Ps＞0.05).In terms of exer-cise regimen,only a single exercise with moderate and high intensity,≤ 20 minutes,and open motor skills could simultaneously improve inhibitory control(SMD=0.47,0.51,0.47,Ps＜0.05)and cognitive flexibility(SMD=0.86,0.65,0.86,Ps＜0.05)in patients with ADHD.Conclusion:Acute exercise could improve inhibitory control and cognitive flexibility in children and adolescents with ADHD,but has no significant effect on working memory and executive function in adult patients.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Adult ; Humans ; Depression ; East Asian People ; Life Style ; Asian People ; China

ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.