Chronic refractory wound （CRW） presents significant clinical treatment challenges due to pathological characteristics such as persistent inflammation， bacterial infection， oxidative stress and inadequate angiogenesis. Astragali Radix， a traditional Chinese medicinal herb， exerts multi-target pharmacological effects on CRW through its active components， including Astragalus polysaccharides， flavonoids， and astragaloside Ⅳ， etc. Fundamental studies indicate that these components promote CRW healing by modulating inflammatory responses， inhibiting pathogen growth， improving antioxidant capacity and stimulating neovascularization. Network pharmacology and bioinformatics studies have revealed that active components of Astragali Radix target and modulate key signaling nodes such as nuclear factor-κB， phosphatidylinositol 3-kinase/Akt， AMP-activated protein kinase， and vascular endothelial growth factor receptor， as well as inflammation-angiogenesis-related pathways， thereby synergistically exerting anti-inflammatory and pro-angiogenic effect. Clinical applications have demonstrated that oral formulations （e.g.， Huangqi guizhi decoction， Danggui huangqi decoction， etc.） reduce healing time of CRW and lower inflammatory marker levels， while topical preparations （e.g.， Zizhu ointment， Huangqi shengji ointment， electrostatically spun Astragalus polysaccharide composite nanofibre dressings， etc.） significantly improve healing rates of CRW and minimize complications.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

AIM:To examine the impact of An-gong Niuhuang pill in conjunction with convention-al therapy on the recovery of neurological function in patients with cerebral hemorrhage(ICH)charac-terized by phlegm-heat internal obstruction,and to evaluate its efficacy in enhancing neurological func-tion,promoting brain tissue repair,and mitigating oxidative stress.Additionally,this study aims to elu-cidate the potential mechanisms underlying these effects through the AMPK-PGC1α-Nrf2 pathway.METHODS:A total of 130 patients with ICH charac-terized by phlegm-heat internal closure were re-cruited and randomly allocated into a control group(receiving conventional treatment)and a study group(receiving Angong Niuhuang pill in combination with conventional treatment)using the random number table method,with 65 cases in each group.Post-treatment assessments included the National Institutes of Health Stroke Scale(NI-HSS)score,Glasgow Coma Scale(GCS)score,modi-fied Rankin scale(mRS)score,as well as tissue lev-els of AMP-activated protein kinase(AMPK),peroxi-some proliferator-activated receptor gamma coacti-vator-1α(PGC1α),and nuclear factor erythroid 2-related factor 2(NRF2).Additionally,serum levels of superoxide dismutase(SOD),malondialdehyde(MDA),reactive oxygen species(ROS),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),inter-leukin-6(IL-6),glutathione peroxidase 4(GPX4),ac-yl-coenzyme A synthetase long-chain family mem-ber 4(ACSL4),iron ions,tumor volume,brain ede-ma volume,and the incidence of adverse reactions were evaluated.RESULTS:Each group comprised 65 cases.Post-treatment,the NIHSS score(9.97±1.22)and mRS score(2.29±0.33)in the Research Group were significantly lower than those in the Control Group(11.17±1.52 and 2.64±0.45,respec-tively),with p-values less than 0.05.Additionally,the GCS score for the Research Group(14.57±1.19)was notably higher compared to the control group(13.18±1.05)(P＜0.05).After treatment,the expres-sions of AMPK[(3.34±0.81)ng/mL],PGC1α[(2.30±0.67)ng/mL]and NRF2[(3.72±0.85)ng/mL]in the tissues of the group were higher than those of the control group[(2.63±0.65)ng/mL,(1.83±0.70)ng/mL,(2.91±0.96)ng/mL](P＜0.05).After treatment,the levels of serum SOD[(98.76±6.67)U/mL]and IL-10[(40.37±5.61)pg/mL]in the research group were higher than those in the Control group group[(89.65±6.89)U/mL,(35.69±4.65)pg/mL](P＜0.05);the serum levels of MDA[(3.36±0.62)nmol/mL],ROS[(126.35±23.74)U/mL],TNF-α[(17.22±2.07)pg/mL]and IL-6[(33.37±3.76)pg/mL]in the group were lower than those in the control group group[(3.76±0.83)nmol/mL,(159.85±26.67)nmol/mL,(19.15±2.34)nmol/mL,(41.26±4.91)nmol/mL](P＜0.05).After treatment,the serum GPX4 level in the Research Group[(9.87±1.25)ng/mL]was higher than that in the control group[(8.16±1.12)ng/mL](P＜0.05).The serum levels of ACSL4[(8.74±1.45)ng/mL]and iron ion[(27.44±3.35)μmol/L]in the study group were lower than those in the control group(10.12±2.11)ng/mL,(30.46±3.17)μmol/L](P＜0.05).After treatment,the hematoma volume[(6.46±1.13)mL]and brain edema volume[(11.47±1.76)mL]in the research group were bet-ter than those in the Control group[(8.71±1.02)mL,(3.41±2.04)mL](P＜0.05).CONCLUSION:The combination of Angong Niuhuang pill with conven-tional treatment demonstrates significant efficacy in improving neurological function,promoting brain tissue repair,and alleviating oxidative stress,thereby exhibiting high application value in clinical practice.

Objective A rat model of cerebral small vessel disease(CSVD)was established by unilateral injection of a single dose of sodium laurate into the internal carotid artery.The effectiveness of the model was assessed by behavior scoring and analysis of serum-related indicators,cerebral infarction volume,cerebral microvascular density,hemodynamics,brain histopathology and the expression of blood-brain barrier(BBB)-related proteins.Methods SPF-grade male SD rats were divided randomly into a control group and a model group(n=6 per group).The model group received a single injection of 100 μL of sodium laurate(2 g/L)via the internal carotid artery,while the control group underwent the same surgical procedure but received an equal volume of saline.Neurobehavioral assessments were conducted using the Longa score and postural reflex test.Serum homocysteine(HCY)levels were measured by enzyme-linked immunosorbent assay.Cerebral infarction volume was detected by magnetic resonance imaging and changes in cerebral vascular density were observed by cerebrovascular imaging.The resistance index(RI)and perfusion index(PI)were measured by ultrasonography.Histopathological changes in brain tissue were evaluated by hematoxylin and eosin(HE)staining.Expression of the cerebral microvascular marker CD31 and tight junction proteins ZO-1 and Occludin in brain cortex tissue were detected by immunohistochemical staining.Results The Longa score,postural reflex score(P＜0.05),and cerebral infarction volume were significantly increased(P＜0.05)while the cerebral vascular density was decreased in the model group compared with the control group.Serum HCY levels,carotid RI,and PI values were all significantly increased in the model group(P＜0.05).HE staining revealed solidified neuronal nuclei and enlarged perivascular spaces in the brain cortex in the model group.Immunohistochemical staining revealed that CD31,ZO-1,and Occludin expression were significantly reduced in the brain cortex in the model group compared with the control group(P＜0.05).Conclusions A rat model of CSVD can be established rapidly and effectively by a single unilateral injection of high-concentration sodium laurate via the internal carotid artery.This model is characterized by neurobehavioral abnormalities,cerebral infarction,insufficient cerebral blood supply,reduced vascular density,and disruption of the BBB,suggesting that it may serve as an effective rat model for the study of CSVD.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

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.