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*

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.

Objective:To observe the effect of stellate ganglion block(SGB)on the inflammatory response in rats with acute peritonitis,and to explore whether the possible anti-inflammatory mechanism related to the activation of α7nAChR receptor-mediated cholinergic anti-inflammatory pathway.Methods:A total of 36 SD rats were randomly divided into three groups,with 12 rats in each group:sham operation group(S group),acute peritonitis group(AP group)and SGB treatment group(SGB group).2%acetic acid(1 ml/100 g)was intraperitoneally injected to prepare acute peritonitis rat model in AP group and SGB group,and corresponding dose of normal saline was injected into S group.Right cervical sympathetic nerve was separated but not ligated in AP group and S group,the right cervical sympathetic nerve was severed and ligated in SGB group.Abdominal aorta blood samples were collected 24 h after opera-tion,and serum levels of IL-1β,IL-6 and TNF-α were measured by ELISA,pathological changes of peritoneal tissue were observed by light microscope and expression of α7nAChR in peritoneal tissue was measured by Western blot.Results:Compared with S group,se-rum levels of IL-1β,IL-6 and TNF-α in AP and SGB groups were significantly increased(P<0.05).Serum levels of IL-1β,IL-6,TNF-α in SGB group were significantly lower than those in AP group(P<0.05).HE staining of peritoneal tissues in each group revealed that the S group maintained intact peritoneal structure with normal cellular arrangement,while the AP group exhibited disorganized archi-tecture with extensive inflammatory cell infiltration,frequent hemorrhage,and prominent necrotic cells.In contrast,the SGB group displayed only mild inflammatory infiltration with preserved cellular morphology and minimal hemorrhagic or necrotic changes.The ex-pression level of α7nAChR protein in SGB group was significantly higher than that in S group and AP group.Conclusion:SGB can re-duce the inflammatory response of acute peritonitis rats,and its mechanism may be related to the cholinergic anti-inflammatory path-way mediated by α7nAChR.

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective:To observe the effect of stellate ganglion block(SGB)on the inflammatory response in rats with acute peritonitis,and to explore whether the possible anti-inflammatory mechanism related to the activation of α7nAChR receptor-mediated cholinergic anti-inflammatory pathway.Methods:A total of 36 SD rats were randomly divided into three groups,with 12 rats in each group:sham operation group(S group),acute peritonitis group(AP group)and SGB treatment group(SGB group).2%acetic acid(1 ml/100 g)was intraperitoneally injected to prepare acute peritonitis rat model in AP group and SGB group,and corresponding dose of normal saline was injected into S group.Right cervical sympathetic nerve was separated but not ligated in AP group and S group,the right cervical sympathetic nerve was severed and ligated in SGB group.Abdominal aorta blood samples were collected 24 h after opera-tion,and serum levels of IL-1β,IL-6 and TNF-α were measured by ELISA,pathological changes of peritoneal tissue were observed by light microscope and expression of α7nAChR in peritoneal tissue was measured by Western blot.Results:Compared with S group,se-rum levels of IL-1β,IL-6 and TNF-α in AP and SGB groups were significantly increased(P<0.05).Serum levels of IL-1β,IL-6,TNF-α in SGB group were significantly lower than those in AP group(P<0.05).HE staining of peritoneal tissues in each group revealed that the S group maintained intact peritoneal structure with normal cellular arrangement,while the AP group exhibited disorganized archi-tecture with extensive inflammatory cell infiltration,frequent hemorrhage,and prominent necrotic cells.In contrast,the SGB group displayed only mild inflammatory infiltration with preserved cellular morphology and minimal hemorrhagic or necrotic changes.The ex-pression level of α7nAChR protein in SGB group was significantly higher than that in S group and AP group.Conclusion:SGB can re-duce the inflammatory response of acute peritonitis rats,and its mechanism may be related to the cholinergic anti-inflammatory path-way mediated by α7nAChR.

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 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 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.