This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Decabromodiphenyl ether(BDE-209)and decabromodiphenyl ethane(DBDPE)are widely used brominated flame retardants,which have been detected in the atmosphere,water,soil,and various organisms.In this study,a method based on high-performance liquid chromatography-inductively coupled plasma-mass spectrometry(HPLC-ICP-MS)was developed for determination of BDE-209 and DBDPE in sediment.Firstly,the target compounds in the sediments were extracted by accelerated solvent extraction(ASE),and the extraction solvent was hexane/dichloromethane(1∶1,V/V).The extract was concentrated by rotary evaporation and purified by a composite silica gel column(6 g neutral silica gel,8 g acidic silica gel,and 4 g anhydrous sodium sulfate),concentrated by nitrogen blowing,and then re-dissolved with 1 mL of toluene for instrumental determination.The chromatographic separation was carried out on a TC-C18(2)column(250 mm×4.6 mm)with isocratic elution using methanol-isopropanol-water(89∶6∶5,V/V)as the mobile phase,and the samples were separated within 20 min.Further,the Br element was quantified by ICP-MS to realize the detection of the target.The results showed that the method established in this study exhibited good linearity(R2>0.999)in the range of 100-10000 ng/mL,and the limits of quantification(LOQs)of the method were 2.0 ng/g for BDE-209 and 10.0 ng/g for DBDPE,with the relative standard deviations(RSDs,n=3)lower than 10%,and the recoveries were in the acceptable range(80.9%-120.7%).The matrix effect was effectively controlled within 10%.In addition,by analyzing the actual sediment samples from Guangxi,a background point,and Taizhou,Zhejiang,a typical contaminated area,it was found that neither BDE-209 nor DBDPE was detected in the sediment from Guangxi,while the concentrations of BDE-209 and DBDPE in the sediment from Zhejiang ranged from 1591.8 to 3362.9 ng/g,which further demonstrated the applicability and reliability of the method for analyzing actual environmental samples.This study provided a strong technical support for the accurate detection of POPs in the environment.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the effect of physical activity on mortality risk in patients with chronic obstructive pulmonary disease (COPD) in Sichuan Province.Methods:Based on baseline data from 2004 to 2008 from the China Kadoorie Biobank project site in Pengzhou City, Sichuan Province, a total of 8 501 COPD patients aged 30-79 years were enrolled and followed up for a long period to determine mortality outcomes. Quartiles were used to group physical activity levels. The Cox proportional hazards regression model was used to analyze the effect of physical activity level on mortality outcomes.Results:As of December 31, 2017, the cumulative follow-up of the participants totaled 85 600.58 person-years (mean follow-up duration: 10.07 years). During this period, a total of 2 000 deaths were recorded, yielding a cumulative mortality rate of 23.53%. Among these deaths, 665 were attributed to COPD, corresponding to a cumulative mortality rate of 7.82%; and 1 116 were attributed to cardiovascular and cerebrovascular disease (CVD), corresponding to a cumulative mortality rate of 13.13%. The Cox proportional hazards regression model analysis revealed that, after adjusting for confounding factors, total physical activity was associated with a reduced risk of mortality from COPD, CVD, and all causes in patients with COPD. Compared with the low-level group of total physical activity, the medium-high-level group had the lowest risk of COPD mortality, with an HR of 0.39 (95% CI: 0.30-0.49). The high-level group had the lowest risk of CVD death and all-cause death, with HRs of 0.46 (95% CI: 0.37-0.56) and 0.55 (95% CI: 0.48-0.64), respectively. The lowest risk of COPD death and CVD death was found in the medium-high level of work-based physical activity group, with HRs of 0.36 (95% CI: 0.28-0.46) and 0.43 (95% CI: 0.36-0.51), respectively; the risk of all-cause mortality was lowest in the medium-high and high-level groups, with HRs values of 0.53 (95% CI: 0.46-0.61) and 0.53 (95% CI: 0.45-0.61). The risk of COPD death was lowest in the high-level transportation physical activity group, with an HR of 0.66 (95% CI: 0.53-0.83), and the risk of CVD and all-cause death was lowest in the medium-high level group, with HRs of 0.63 (95% CI: 0.53-0.76) and 0.73 (95% CI: 0.64-0.84), respectively. The risk of COPD death and CVD death was the lowest in the high-level domestic physical activity group, with HRs of 0.66 (95% CI: 0.49-0.89) and 0.76 (95% CI: 0.61-0.95), respectively, and the risk of all-cause death was the lowest in the medium-high level group, with an HR of 0.82 (95% CI: 0.72-0.94). There is no statistical association between leisure physical activity and the risk of death from three types of diseases. Conclusions:Total physical activity, including work-based, transportation-based, and domestic physical activity, reduced the risk of COPD, CVD, and all-cause mortality in patients with COPD in Sichuan Province. The magnitude of mortality risk was influenced by the type and level of physical activity.

Objective:To explore the natural course of ulcerative proctitis (UP) and the risk factors associated with disease extent progression.Methods:A retrospective cohort study was conducted, including UP patients who had undergoing prospective regisration in the Department of Gastroenterology, Xijing Hospital of Digestive Diseases, Air Force Medical University between January 2000 and May 2023. All patients were ≥ 18 years old at the time of diagnosis and followed up for more than one year. The disease extent in patients at diagnosis and during follow-up was assessed according to the Montreal classification. The clinical data were compared between the progression group and the non-progression group. The cumulative proportions of disease extent progression were analyzed with the Kaplan-Meier method, and the risk factors associated with disease extent progression were analyzed with the Cox proportional hazards regression model.Results:A total of 184 UP patients were included, with a median follow-up time of 4.8 (2.8, 8.5) years. Among them, 96 were male (52.2%) and 88 were female (47.8%), with a median age at diagnosis of 39.1 (28.8, 49.7) years. At the time of diagnosis, 95 (51.6%) patients had moderate endoscopic manifestations and 64 (34.8%) had severe endoscopic manifestations, while only 25 (13.6%) patients had mild lesions. 116 patients (63.0%) experienced disease extent progression in a median time of 4.2 (1.8, 9.0) years. The cumulative proportions of disease extent progression in 1, 3, 5, and 10 years were 13.0%, 39.0%、56.7% and 78.3%, respectively. Cox regression analysis identified the use of 5-aminosalicylic acid as a protective factor against disease extent progression ( HR = 0.55, 95% CI: 0.31 ~ 0.96, P = 0.035). During follow-up, only one patient (0.5%) underwent surgery. Five patients (2.7%) were diagnosed with dysplasia, and all of these patients had experienced disease extent progression before the development of dysplasia. Conclusions:Patients with UP had a high proportion of moderate-to-severe active endoscopic findings at diagnosis, and nearly two-thirds of patients experienced disease progression during follow-up, but the rates of colectomy and neoplasia were relatively low. 5-ASA was a protective factor against disease extent progression.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.