ObjectiveTo screen suitable packaging and storage conditions for small packaged Alismatis Rhizoma decoction pieces， laying the foundation for developing standardized storage， maintenance techniques and determining shelf life. MethodsUsing the accelerated stability test method， the small packaged decoction pieces of Alismatis Rhizoma were placed in polyethylene plastic bags， aluminum foil polyethylene composite bags， and cowhide coated paper bags under temperature of （40±2） ℃ and relative humidity of （75±5）% conditions， the quality testing was conducted at the end of the 0^th， 1^st， 2^nd， 3^rd， and 6^th month， respectively. Using long-term stability test method， an orthogonal experiment was designed to investigate storage conditions， packaging materials， and packaging methods. At the end of the 0^th， 1^st， 3^rd， 6^th， 9^th， 12^th， 18^th， and 24^th month， the quality of small packaged Alismatis Rhizoma decoction pieces was tested under different packaging and storage conditions（including 2 packaging methods：vacuum packaging and sealed packaging， 3 storage conditions：room temperature， cool， and modified atmosphere， 3 packaging materials：cowhide coated paper bag， aluminum foil polyethylene composite bag， and polyethylene plastic bag）. Then， the G1-entropy weight method combined with orthogonal experiment was used to analyze the quality changes of the decoction pieces under different packaging and storage conditions to identify optimal packaging and storage conditions. The quality testing indicators for Alismatis Rhizoma decoction pieces were expanded beyond those specified in the 2020 edition of the Pharmacopoeia of the People's Republic of China. In addition to the existing indicators（characteristics， moisture content， extractives， and the total content of 23-acetyl alisol B and 23-acetyl alisol C）， new indicators including color value， water activity， total triterpenoid content， and alisol B content have been added. ResultsThe accelerated stability test results indicated that the quality of small packaged Alismatis Rhizoma decoction pieces was more stable when packaged in aluminum foil-polyethylene composite materials compared to cowhide-coated paper bags and polyethylene plastic bags. Analysis of the long-term stability test results using the G1-entropy weight method combined with orthogonal experiment revealed that storage conditions had the greatest impact on both raw and salt-processed products， followed by packaging materials， while the packaging method had the least influence. For both types of small packaged Alismatis Rhizoma decoction pieces， modified atmosphere storage demonstrated superior efficacy compared to cool storage or room temperature storage. Storage in aluminum foil-polyethylene composite bags was superior to polyethylene plastic bags or cowhide-coated paper bags. However， the stability of sealed raw products was better than vacuum-packed ones， whereas vacuum-packed salt-processed products exhibited greater stability than their sealed counterparts. ConclusionBased on the results of the quality changes of small packaged Alismatis Rhizoma decoction pieces under different storage conditions， it is recommended that the suitable storage packaging conditions for small packaged raw products are sealed packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage， and the suitable storage and packaging conditions for small packaged salt-processed products are vacuum packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective:To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region.Methods:268 infants presented at the Women and Children′s Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017).Results:Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). Conclusion:WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To compare gamma pass rates for ultra-long target volumes of cervical cancer between individual measurements by moving the phantom isocenter and segmented measurements combined with merging and to assess the influence of scattering blocks on verification result during segmented measurements.Methods:A retrospective study was conducted on 24 cervical cancer patients with ultra-long target volumes (lengths: 23.5–36.0 cm) treated using helical tomotherapy. Two measurement methods were used to verify the gamma pass rates: individual measurements by moving the phantom isocenter and segmented measurements combined with merging. For the first measurement method, the patients′ treatment plans were transferred to the ArcCheck phantom. After the dose distribution was calculated and exported, the gamma pass rates measured and calculated were compared. For the segmented measurements, a 50-cm-long virtual phantom was imported, and the treatment plans of patients were then transferred to the virtual phantom. Afterward, the dose distribution of the virtual phantom was calculated and exported. Then, two dose measurements were conducted under upward and downward setup of the ArcCheck phantom. Two dose measurement files were obtained and then fused to produce a merged file. Then, the γ pass rates were calculated. Repeated measurements were conducted after scattering blocks were installed. The γ-pass rates were assessed using varying dose criteria.Results:Under various evaluation criteria, no statistically significant differences in γ pass rates were observed between the individual measurements by moving the phantom isocenter and the segmented measurement in the presence of scattering blocks ( P > 0.05). In contrast, there existed statistically significant differences in γ pass rates between the individual measurements by moving the phantom isocenter and the segmented measurement in the absence of scattering blocks according to the (global) criterion of 3%/2 mm absolute dose ( Z = -2.31, P = 0.02). Additionally, the segmented measurement in the presence of scattering blocks enhanced pass rates, with statistical significant difference under the criterion of 3%/2 mm relative dose ( Z = -2.11, P = 0.04). Conclusions:In the case where ArcCheck is used to measure the dose distribution of ultra-long target volumes in cervical cancer, it is advisable to preferentially use individual measurements by moving the phantom isocenter. When segmented measurements combined with merging are required, it is necessary to install scattering blocks during measurements. This will improve γ-pass rates during verification and ensure the accuracy of dose verification.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective To investigate the immediate therapeutic efficacy of Kuanxiong Aerosol on improving the angina pectoris in the patients complicated with intermediate coronary stenosis(ICS),and to observe its effect on resting full-cycle ratio(RFR),corrected TIMI(thrombolysis in myocardial infarction)frame count(CTFC)in angiography,and coronary serum inflammatory factors.Methods Sixty angina pectoris patients with ICS admitted to the Cardiovascular Department of Dade Road Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2023 to March 2024 were randomly divided into the trial group and the control group,with 30 patients in each group.The trial group was given four consecutive sprays of Kuanxiong Aerosol by sublingual spray,and the control group had no intervention but just was given the monitoring for 10 minutes.Before and after the intervention,the changes of coronary RFR,CTFC,Visual Analogue Scale(VAS)score of chest pain,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6)and lipoprotein-associated phospholipase A2(Lp-PLA2)in the two groups were observed.Moreover,the incidence of adverse reactions during the intervention in the two groups of patients was compared.Results(1)After the intervention,the coronary RFR value of the trial group was increased significantly compared with that before intervention(P<0.01),while the coronary RFR value of the control group was not increased significantly compared with that before intervention(P>0.05);the comparison between the two groups showed that the effect on increasing the coronary RFR value in the trial group was superior to that in the control group(P<0.05).(2)After intervention,the CTFC value of the trial group was significantly decreased compared with that before intervention(P<0.01),while the CTFC value of the control group was not significantly decreased compared with that before intervention(P>0.05);the intergroup comparison showed that the trial group tended to have a better effect on the decrease of CTFC value than the control group,but the difference being not statistically significant(P>0.05).(3)After the intervention,the chest pain VAS score of the trial group was significantly reduced compared with that before intervention(P<0.01),while the pre-and post-treatment changes of the score in the control group was not significant(P>0.05);the intergroup comparison showed that the decrease of the chest pain VAS score in the trial group was superior to that in the control group(P<0.01).In particular for immediate therapeutic efficacy,Kuanxiong Aerosol achieved the effective rate of 96.67%(29/30)for relieving chest pain 10 minutes after sublingual spraying,which was significantly superior to that of the control group[10.00%(3/30)],and the comparison between the two groups showed that the difference was statistically significant(P<0.001).(4)After the intervention,the Lp-LPA2 value of the trial group was decreased compared with that before intervention(P<0.05),while the CRP and IL-6 values of the trial group as well as the CRP,IL-6,and Lp-LPA2 values of the control group were all not significantly decreased compared with those before intervention(P>0.05).The intergroup comparison showed that the trial group's effect on the decrease of Lp-LPA2 value was significantly superior to that of the control group(P<0.05).(5)Before and after the intervention,no obvious changes of the general vital signs in the two groups were shown,no drug-related adverse occurred,either.Conclusion Kuanxiong Aerosol can immediately improve the coronary physiological function indicators of angina pectoris patients with ICS,increase the coronary flow rate,and inhibit inflammatory response of the coronary artery to some degree,thus to alleviate the symptoms of angina pectoris in patients with ICS.