Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

OBJECTIVE: To observe the clinical efficacy of Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction on acute pharyngitis with lung-stomach heat accumulation. METHODS: A total of 88 patients with acute pharyngitis of lung-stomach heat accumulation were randomly divided into an observation group (44 cases, 4 cases dropped out) and a control group (44 cases, 4 cases dropped out). The control group was treated with oral Qingyan Lige decoction, 150 mL each time, twice a day for 6 continuous days. On the basis of the treatment in the control group, Xujiang Xie's bloodletting therapy was applied at bilateral Shaoshang (LU11), Shangyang (LI1), and Erjian (EX-HN6) in the observation group, 0.1-0.5 mL of bloodletting per site, once every other day for 3 times in total. The TCM symptom and sign score, complete blood count (white blood cell [WBC] count, neutrophilic granulocyte percentage [NE%]), inflammation indexes (serum levels of C-reactive protein[CRP], interleukin[IL]-1β, IL-6, tumor necrosis factor [TNF]-α) and immune indexes (？？, ？？, ？？) of the two groups were observed before treatment and after 6 days of treatment, and the clinical efficacy was evaluated. RESULTS: After 6 days of treatment, the sore throat scores, redness and swelling scores of pharyngeal mucosa and uvula, pharyngeal dry and burning scores, hyperemia scores of posterior pharyngeal lymphoid follicles, chill and fever scores, total scores of TCM symptom and sign, WBC count, NE%, CRP, IL-1β, IL-6, TNF-α and ？？ in both groups were decreased compared with those before treatment (P<0.05), the above indexes in the observation group were lower than those in the control group (P<0.01, P<0.05, P<0.001). After 6 days of treatment, the levels of ？？ and ？？ in both groups were increased compared with those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.001). The total effective rate of the observation group was 95.0% (38/40), which was higher than 90.0% (36/40) in the control group (P<0.001). CONCLUSION Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction could improve the symptoms in patients with acute pharyngitis of lung-stomach heat accumulation, inhibit inflammatory response and improve immune function.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Pharyngitis/drug therapy* ; Adult ; Middle Aged ; Bloodletting ; Young Adult ; Lung/drug effects* ; Combined Modality Therapy ; Interleukin-6 ; Adolescent ; Tumor Necrosis Factor-alpha ; Acute Disease/therapy* ; Treatment Outcome

Objective:To investigate the role of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) in enamel development of mice.Methods:Single-cell RNA sequencing data of incisor tissues of postnatal day 7 (P7) mice and mandibular first molar tooth germs of P3.5 mice were used to analyze the expression of Wwp1 in dental epithelial cells. Immunohistochemistry was performed to observe the distribution and expression levels of WWP1 in the epithelium of mouse incisors and mandibular first molar tooth germs. Wwp1 knockout (Wwp1 KO) mice were generated and collected with their control littermates at P1, P7, three mice per group, as well as at P14, P28, 2 months (2M), and 3M, six mice per group. The enamel volumes of molars and incisors were analyzed using micro-CT. Scanning electron microscopy was employed to examine the enamel cross-sections of Wwp1 KO and control mice. Energy dispersive spectroscopy (EDS) was used to analyze the calcium and phosphorus content of the enamel rod of incisors. Immunofluorescence was performed to detect the expression of amelogenin (AMELX) in the ameloblasts of Wwp1 KO and control mice. Additionally, LS-8 ameloblast-like epithelial cells were cultured, and Wwp1 siRNA or overexpression plasmids were transfected to knock down or overexpress WWP1. The protein levels of AMELX were then assessed by Western blotting.Results:Single-cell sequencing result showed a high Wwp1 mRNA expression level in the epithelial cells of mouse incisors and mandibular molar tooth germs. Immunohistochemistry revealed the expression of WWP1 in presecretory, secretory, transitional, and mature ameloblasts. Wwp1 KO mice exhibited enamel developmental defects. The enamel volumes of molars and incisors in Wwp1 KO mice [(0.155±0.016), (0.300±0.017) μm 3] were reduced by 23.95% ( P<0.001) and 28.31% ( P<0.001) compared with the control group [(0.203±0.062), (0.418±0.023) μm 3] respectively. Scanning electron microscopy showed disorganized enamel structures in Wwp1 KO incisors and molars. EDS results showed the weight percent of calcium in the enamel rod of incisors decreased in Wwp1 KO mice [(20.74±0.91)%] compared with the control group [(30.30±3.83)%] ( P<0.001), and the calcium-to-phosphorus ratio decreased in Wwp1 KO mice (1.93±0.01) compared with the control group (2.02±0.01) ( P<0.001). Immunofluorescence showed weaker AMELX expression in ameloblasts of mandibular first molar tooth germs from P1 and P7 Wwp1 KO mice compared with the control group ( P<0.001, P<0.001). In LS-8 cells, Wwp1 knocked-down led to a decrease of AMELX protein expression, while WWP1 overexpression resulted in an increased AMELX protein level. Conclusions:WWP1 promotes ameloblast differentiation and enamel matrix mineralization, playing a critical role in enamel formation.

Pre-eruptive intra-coronal resorption is a rare intra-coronal dental disorder that typically emerges prior to tooth eruption. The radiological images show a well-demarcated low-density translucent area within the dentin adjacent to the enamel-dentin junction. This lesion is often accidentally discovered by radiological examinations. It may even progress to enamel and the dentin of the root. Currently, there is a considerable variation in the reported prevalence of this lesion. Its pathogenic mechanisms have not been fully revealed, and there is lack of systematic clinical management strategies. This article provides a comprehensive review of the pre-eruptive intra-coronal resorption, and aims as a reference for dentists to improve their understanding of this lesion, and to facilitate its early detection, early diagnosis and timely treatment.

Objective:To investigate the role of mRNA expression in the pathogenesis of gout by analyzing the difference of gene expression in peripheral blood mononuclear cells(PBMCs)among acute gouty(AG),intermittent gouty(IG)and health con-trols(HC).Methods:AG patients,IG patients and HC were enrolled in this study.RNA-seq and bioinformatics techniques were used to observe the differences of mRNA expression in PBMCs of different groups,and to explore the genes and signaling pathways as-sociated with gout attack.GO and KEGG databases were used to investigate the biological functions of differentially expressed genes and the relationship between genes and signaling pathways.Genes involved in the KEGG enriched PPAR signaling pathway(CYP27A1,ACSL1,CD36,PPARG,ANGPTL4,PLIN2)were validated in PBMCs from 35 patients with AG,35 patients with IG,and 35 normal healthy subjects using real-time PCR.Results:Compared with HC group,there were 222 significant differential genes in AG group,including 193 up-regulated genes and 29 down-regulated genes.GO analysis showed that the genes differentially ex-pressed in AG group were mainly enriched in the regulation of multicellular biological processes such as inflammation,trauma,and stress response and immune response regulation compared with HC group.However,KEGG analysis showed that the up-regulated genes in AG group were enriched in"Toll-like receptor signaling pathway""complement and coagulation cascades""PPAR signaling pathway""lipid and atherosclerosis""osteoclast differentiation""cytokine-cytokine receptor interaction""chemokine signaling path-way""IL-17 signaling pathway",and"cholesterol metabolism"compared with HC group.The results of PCR validation of related genes in the PPAR signaling pathway showed that the expression levels of ACSL1,CD36,PPARG,and PLIN2 in the AG group were higher than those in the control group(P<0.05),and the expression levels of CYP27A1 and ANGPTL4 in the AG group were not dif-ferent from those in the HC group(P>0.05).Conclusion:PPAR signaling pathway may be involved in the pathogenesis of AG,of which ACSL1,CD36,PPARG,and PLIN2 may be used as potential therapeutic targets for acute gouty arthritis;CYP27A1 and ANG-PTL4 may not be associated with the pathogenesis of AG.

Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.