Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.
Humans ; DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Deafness/genetics* ; Hearing Loss/genetics* ; Phenotype ; Genotype ; Nucleotides ; Pedigree ; Mutation ; GPI-Linked Proteins/genetics*

Humans ; Otosclerosis/surgery* ; Stapes ; Stapes Surgery/adverse effects* ; Arteries

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Numerous studies showed that the growth of medicinal plants in their native areas was simultaneously affected by abiotic stress combinations. Compared with single stress, plants have unique responses to a combination of different abiotic stresses and cannot be inferred directly from plants' responses to each individual stress. The effect of combined stresses on plants usually has three types of synergistic antagonism or independence. The secondary metabolism in the process of medicinal plant stress combination response also played a vital role, and environmental stresses can spur the accumulation of secondary metabolites, but under the stress combination, plants induce specific gene expression of key enzymes on secondary metabolic pathways, in turn, the accumulation of secondary metabolites against stress is formed. When plants are subjected to stress combination, the interaction of multiple signaling pathways makes it highly complex for plants to respond to stress combination. This paper summarized the effects of stress combination on physiological and secondary metabolism of medicinal plants, and discussed the related physiological, biochemical and molecular mechanisms. It provides theoretical basis for improving the adaptability of medicinal plants to adversity, improving the quality of Chinese medicinal materials, and further optimizing the cultivation of medicinal plants.
Gene Expression Regulation, Plant ; Metabolic Networks and Pathways ; Plants, Medicinal ; Secondary Metabolism ; Stress, Physiological

Rhizosphere bacteria play a vital role in plant nutrition absorption,growth and disease resistance. In this study,high-throughput sequencing technology was used to analyze the rhizosphere bacterial communities of Salvia miltiorrhiza and S. miltiorrhiza f. alba. Moreover,the function of dominant rhizosphere bacterial communities was analyzed. We found that Sphingobacteriales,Sphingomonadales and Nitrosomonadaceae were both dominant and specific bacteria in the rhizosphere of S. miltiorrhiza. The main functions of dominant rhizosphere bacteria communities in both species include promoting transformation of soil nutrients,improving plant immunity and ability of stress tolerance. This study was the first to compare rhizobacterial communities structure and function of S. miltiorrhiza and S. miltiorrhiza f. alba,which provided a new theoretical reference for studing the rhizosphere mechanism of healthy S. miltiorrhiza planting in the future.
Bacteria ; classification ; High-Throughput Nucleotide Sequencing ; Rhizosphere ; Salvia miltiorrhiza ; microbiology ; Soil Microbiology

BackgroundSleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.

MethodsWe recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.

ResultsThe mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO(r = -0.323, -0.315, both P = 0.001) in PD patients.

ConclusionsThe level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Aged ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease ; blood ; physiopathology ; Polysomnography ; Sleep Wake Disorders ; blood ; physiopathology

Objective: To investigate the current status of antithrombotic strategy for elderly patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) after stent implantation in Beijing area and to study the safety and efficacy of different therapeutic strategy. Methods: A total of 467 relevant patients were enrolled by re-travelling electronic medical records from 12 hospitals in Beijing area. The patients' mean age was (78.70±3.32) years and they were divided into 2 groups by antithrombotic therapy condition: Triple therapy group, n=17 (3.64％), Double therapy group, n=450 (96.36％). The incidence of major adverse cardiac and cerebral events (MACCE) including all-caused death, non-fatal myocardial infarction, stent thrombosis, target vessel revascularization (TVR), stoke and bleeding was compared between Triple therapy group and Double therapy group.Results: The medication in Double therapy group included aspirin+ticagrelor, aspirin+clopidogrel, clopidogrel+warfarin and cilostazol+clopidogrel; in Triple therapy group was aspirin+clopidogrel+warfarin. Patient with HAS-BLED score≥3 was defined as high risk of bleeding and they were all treated by double therapy; HAS-BLED<3 was defined as low risk of bleeding, only 5.03％ patients were treated by triple therapy. 3 patients in Triple therapy group and 33 in Double therapy group suffered from gastrointestinal bleeding, P=0.338; 6 patients in Triple therapy group and 128 in Double therapy group had MACCE, P=0.589; 3 and 80 patients died in Triple therapy group and Double therapy group, P=0.766. Conclusion: Triple therapy was rarely used in elderly AF and ACS patients after stent implantation, double therapy was the main strategy; the incidence of MACCE and mortality were similar between triple and double therapies; patients with triple therapy had the higher incidence of gastrointestinal bleeding.