BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

Circadian rhythm is a biological endogenous process regulated by the suprachiasmatic nucleus of the hypothalamus, which transmits light signals to peripheral clocks and synchronizes the body with the external environment through balanced expression of circadian rhythm genes. Working the night shift, sleep disorders, and exposure to artificial light can lead to disturbances in circadian rhythm and genetic imbalances. A substantial body of research has demonstrated that circadian rhythm plays a significant role in the treatment of autoimmune diseases and neurodegenerative disorders, with increasing attention being directed toward their impact on oral health. Disturbances in circadian rhythm primarily affect psycho-neuro-immune mechanisms, oxidative stress responses, and oral microflora through pathways such as the hypothalamic-pituitary-adrenal axis (HPA axis), brain and muscle ARNT-like 1 (BMAL1)-brain-derived neurotrophic factor (BDNF) signaling, and BMAL1-nuclear factor kappa-B (NF-κB) interactions. These disruptions may influence the progression of oral diseases. Certain pharmacological agents (e.g., melatonin, vitamin D, nobiletin, and propofol) have been shown to regulate mood disorders, immune function, and sleep-wake cycles by upregulating BMAL1 expression, thus alleviating disturbances in circadian rhythm. In addition, non-pharmacological interventions, such as sleep management strategies, psychotherapy approaches, and light therapy, also modulate these processes through HPA axis regulation. Currently, the specific mechanisms by which circadian rhythm regulates BDNF levels, T cell subsets, and inflammatory signals—thereby influencing both pathogenesis and treatment outcomes for oral diseases—remain unclear. Future research should focus on elucidating these molecular mechanisms as well as identifying therapeutic targets related to circadian rhythm within the oral health context. Further, multidisciplinary collaboration encompassing pharmacy, sleep behavior studies, and psychology will be instrumental in advancing prevention strategies and treatments for oral diseases.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

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 observe the effect of stellate ganglion block(SGB)on serum inflammatory factors and the expression of α7nAChR protein in rats with acute peritonitis,so as to further explore the mechanism of SGB on the inflammatory response of acute peritonitis in rats.Methods:40 SPF grade male rats were randomly divided into 4 groups:blank group(Control),acute peritonitis group(AP),acute peritonitis+stellate ganglion block group(AP+SGB),acute peritonitis+stellate ganglion block+α7nAChR inhibitor methyllycaconitine group(AP+SGB+MLA),with 10 rats in each group.Inject 2％acetic acid at a dose of 1 ml/100 g into the peritoneal cavity of rats to establish an acute peritonitis model in the AP group,AP+SGB group,and AP+SGB+MLA group.Blood samples were collected from the tail vein of the rats,and the concentrations of IL-18 and TNF-α in serum were detected by ELISA.Western Blot method was used to detect the level of α7nAChR protein in the peritoneal tissues,and RT-qPCR method was used to detect the expression of α7nAChR mRNA in the peritoneal tissues.Results:Compared with Control group,the levels of IL-18 and TNF-α were increased in the other three groups(P＜0.05).Compared with AP group,serum levels of IL-18 and TNF-α in AP+SGB group were decreased(P＜0.05).Compared with AP+SGB group,serum levels of IL-18 and TNF-α were increased in AP+SGB+MLA group(P＜0.05).The expression of α7nAChR mRNA protein were higher in the three groups than group Control,(P＜0.05).Compared with AP group,α7nAChR protein and α7nAChR mRNA expression levels were higher in AP+SGB group and AP+SGB+MLA group(P＜0.05).Compared with AP+SGB group,α7nAChR protein and α7nAChR mRNA expression levels in AP+SGB+MLA group were lower(P＜0.05).Conclusion:Stellate ganglion block treatment can reduce the production of inflammatory factors and inhibit the inflammatory response of acute peritonitis in rats,and its anti-inflammatory mechanism may be related to the cholinergic anti-inflammatory pathway(CAP)mediated by α7nAChR.

【Objective】 To investigate the effect of clinical factors and inflammatory markers on platelet transfusion refractoriness (PTR) in children with chemotherapy- induced thrombocytopenia (CIT) and evaluate their predictive value, so as to provide reference for mechanism study of PTR caused by non-immune factors in children with cancer and provide clinical guidance for reasonable and effective platelet transfusion in children. 【Methods】 A total of 60 CIT pediatric cancer patients from Children’s Hospital, Zhejiang University School of Medicine between November 2022 and February 2024 were selected as the study subjects, and divided into the PTR group (n=30) and the non-PTR group (n=30) to collect the clinical data and laboratory markers before platelet transfusion (Plt). Univariate and multivariate logistic regression analysis was used to analyze the influencing factors of PTR. The predictive value influencing factors of PTR was analyzed by receiver operating characteristic (ROC) curve. 【Results】 Plasma IL-1β concentration in PTR group was significantly higher than that in non-PTR group[67.43 pg/mL (29.38, 222.40) vs 36.38 pg/mL (17.27, 68.06); P<0.05]; plasma IL-8 concentration in PTR group was significantly higher than that in non-PTR group[60.97 pg/mL (39.07, 112.00) vs 25.23 pg/mL (5.00, 71.38); P<0.01]; and the interval from initiation of chemotherapy to platelet transfusion was significantly higher in the PTR group than in the non-PTR group[9.5 d (8.0, 12.0) vs 12.0 d (9.8, 13.2); P<0.05]. Multivariate logistic regression analysis showed that IL-8 concentration (OR=1.05, P<0.05) had a statistically significant effect on the occurrence of PTR. ROC curve analysis showed that plasma IL-1β concentration (Cut-off value: 64.88 pg/mL; AUC: 0.653[95% CI: 0.511-0.796]) and plasma IL-8 concentration (Cut-off value: 33.33 pg/mL; AUC: 0.754[95% CI: 0.631-0.878]) and the interval from initiation of chemotherapy to platelet transfusion (Cut-off value: 11.5 days; AUC: 0.669[95% CI: 0.529-0.810]) were statistically significant in predicting PTR. 【Conclusion】 Plasma IL-8 concentration is an independent risk factor for PTR, and plasma IL-1β, IL-8 concentration and interval from initiation of chemotherapy to platelet transfusion have predictive value for PTR.

ObjectiveTo validate the efficacy of Yunpi Huatan Tongqiao prescription （YHTP） in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea （OSA） mice. MethodForty-eight male Balb/C mice were randomly divided into a normal group， a model group， a montelukast sodium group （30 mg·kg^-1）， and low， medium， and high dose groups of YHTP （8.28， 16.56， and 33.12 g·kg^-1）， with 8 mice in each group. All groups， except the normal group， received intraperitoneal injections of lipopolysaccharide （LPS） and underwent chronic intermittent hypoxia （CIH） modeling for 4 weeks. Subsequently， the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and markers such as T lymphocyte activation antigen （CD86） and inducible nitric oxide synthase （iNOS）， as well as M2-associated inflammatory factors interleukin-10 （IL-10）， transforming growth factor-β （TGF-β）， and the marker mannose receptor （CD206） in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers （CD86， CD206） and glycolysis-related proteins glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phosphofructokinase （PFKM）， pyruvate kinase 2 （PKM2）， and monocarboxylic acid transporter 1 （MCT1）. ResultBehavioral tests showed that compared to the results in the normal group， the Y-maze autonomous alternation rate was significantly reduced in the model group （P<0.01）. The latency time for the target hole in the Barnes' maze during the training period （days 2， 3， 4） and testing period （days 5， 12） was significantly increased （P<0.05， P<0.01）. M1 glial cell markers CD86 and iNOS， as well as inflammatory factors IL-1β and TNF-α mRNA， were significantly elevated （P<0.01）. In contrast， the mRNA expression of M2 glial cell markers IL-10， CD206， and TGF-β was significantly reduced （P<0.01）. The protein expression of glycolytic proteins HK2， PFKM， PKM2， MCT1， and the M1 marker CD86 was significantly increased （P<0.05， P<0.01）， while M2 marker CD206 protein expression was significantly decreased （P<0.01）. Compared to the results in the model group， the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP （P<0.05， P<0.01）. The latency time for the target hole during the training （day 4） and testing periods （days 5， 12） was significantly reduced （P<0.01）. Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low， medium， and high dose groups of YHTP （P<0.01）， while M2-related inflammatory factors' mRNA expression was significantly increased （P<0.01）. Western blot results showed that in the medium and high dose groups of YHTP， the expression of the M1 marker CD86 in the hippocampus was reduced， whereas the expression of the M2 marker CD206 was significantly increased （P<0.01）， with a significant decrease in the expression of glycolysis-related proteins （P<0.01）. ConclusionYHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia， inhibiting M1 activation， reducing pro-inflammatory factor release， and promoting M2 activation， thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To construct and apply a multidrug-resistant bacteria information management system,and evaluate its effectiveness and accuracy in the management of patients with multidrug-resistant bacteria infection.Methods A system construction team was established to develop a multidrug-resistant bacteria information management system,which includes 4 modules:early warning,execution,monitoring,and statistical decision-making.Patients with positive detection of multidrug-resistant bacteria admitted to a tertiary A obstetrics and gynecology hospital in Zhejiang Province from January to December 2022,members of the system construction team,and clinical medical staff were selected as the research subjects.The execution efficiency of multidrug-resistant bacteria management,as well as the system's accuracy,usability,and satisfaction were compared before(January to June 2022)and after(July to December 2022)the application of the system.Results After the implementation of the system,the immediate feedback rate of multidrug-resistant bacteria early warning information increased from 62.87％to 89.78％;the rate of issuing isolation medical orders rose from 61.07％to 93.33％;the accuracy of the implementation of isolation measures for patients increased from 66.67％to 98.01％;all differences are statistically significant(P＜0.001).The accuracy rate of the system in making decisions is 88.44％;the usability score given by medical staff for the system is 44.04 points,and the satisfaction score of the system construction team members and medical staff to the system is 121.25 points,both at a high level.Conclusion The multidrug-resistant information management system is equipped with features such as immediate alerts,multi-channel notifications,infection control department supervision,and auxiliary decision-making,which can provide medical staff with accurate decision reports.Preliminary application results show that the system has a high level of accuracy and good usability.

Objective To compare the anesthetic effects of remazolam and dexmedetomidine assisted sedation in the operation of finger replantation under ultrasound guided brachial plexus block.Methods 60 patients undergoing severed finger replantation were randomly divided into remazolam group(group R)and a dexmedetomidine group(group D)by random number table method,with 30 cases in each group.Both groups received a single brachial plexus block under ultrasound guidance.Group R was injected with remazolam 0.1 mg/kg,followed by 1 mg/(kg·h)pump until 10 min before the end of the operation.In group D,a load dose of 0.5 μg/kg of dexmedetomidine was injected,followed by continuous infusion at a rate of 0.5 μg/(kg·h)until 10 min before the end of surgery.The MAP,HR and SpO2 values of the two groups were compared when the patients entered the room(T0),the wound was cleaned and disinfected(T1);the tourniquet was upper(T2);the operation began(T3);the tourniquet was relaxed(T4);and the operation ended(T5).MOAA/S scores and BIS values were compared between the two groups at different time.The time from the beginning of medication to the absence of consciousness and the time of consciousness recovery after drug withdrawal were compared between the two groups.Blood lactic acid(Lac)before applying tourniquet and 15 min after relaxing tourniquet were compared between the two groups.The occurrence of intraoperative adverse reactions was recorded in the two groups.Results The MAP of patients in group R had little fluctuation at each time during the operation,and the MAP of patients in group D was significantly increased at T1,T2,T3 and T0 moments and at the same time as that in group R(P<0.05);HR in group R was stable at all times,and HR in group D significantly slowed down at T1,T2 and at the same time with group R(P<0.05).Patients in both groups achieved ideal sedation during the operation(MOAA/S score≤3 points),and the MOAA/S score of patients in group R at T5 minutes after drug withdrawal was higher than that at other moments of the same group and group D(P<0.05);the BIS value of group R was higher than that of group D(P<0.05).The loss time and recovery time of consciousness in group R were shorter than those in group D(P<0.05).The incidence of intraoperative hypertension and bradycardia in group D was significantly higher than that in group R,and the incidence of respiratory depression in group R was higher than that in group D(P<0.05).There was no significant change in lactate value between the two groups(P>0.05).Conclusion Remazolam and dexmedetomidine can satisfy sedation in brachial plexus nerve block for replantation of severed finger under ultrasound guidanc.Compared with dexmedetomidine,remazolam has better sedation control,stable hemodynamics,low incidence of circulatory adverse events.