Zoledronic Acid-Treated Rats Show Altered Jaw Histology and Gene Expression in Nonexposed Medication-Related Osteonecrosis of the Jaws.

BACKGROUND: Diagnosis and management of medication-related osteonecrosis of the jaws (MRONJ) prior to clinical exposure induced by trauma may lead to improved patient management. Currently, few studies have examined early histologic and molecular MRONJ-related changes in the jaws. PURPOSE: This study aimed to identify histological and gene expression changes in the maxilla and mandible of Sprague-Dawley (SD) rats after zoledronic acid (ZA) treatment. STUDY DESIGN, SETTING, AND SAMPLE: This was an in vivo animal study. The experiments were conducted in the laboratory at the Stomatology Hospital of Tianjin Medical University. A total of 12 SD rats were included. PREDICTOR VARIABLE: The predictor variable was ZA exposure. Twelve SD rats were divided into 2 groups: experimental (n = 6) and control (n = 6), and they were intraperitoneally injected with ZA and saline, respectively. MAIN OUTCOME VARIABLE: The outcome variables were histological and molecular changes. The maxilla, mandible, and ilium bone tissue samples were examined using Masson's trichrome and hematoxylin-eosin staining. Gene expression changes were identified using transcriptome sequencing, the Kyoto encyclopedia of genes and genomes, and gene interactome network analysis. The key changes were validated using the quantitative real-time polymerase chain reaction and immunohistochemistry. COVARIATES: None. ANALYSES: The t-test, χ2 test, and Fisher's exact probability method were used for statistical analyses using the Statistical Package for the Social Sciences software (version 26.0). RESULTS: All animals remained healthy during the experiments. Histological staining revealed that the percentage of empty bone lacunae in the maxilla and mandible was significantly higher than that in the ilium (P < .01). In total, 552 genes were screened using transcriptome sequencing. The sonic hedgehog (Shh) signaling pathway was highly enriched. The key gene for the Shh interaction was distal-less homeobox 5. The Shh, distal-less homeobox 5, and bone morphogenetic protein 2 genes and protein expression levels in the maxilla and mandible were higher in the experimental group than in the control group (P < .05). CONCLUSION AND RELEVANCE: MRONJ-induced osteonecrosis and gene expression changes precede trauma-induced clinical changes in the SD rat model. These findings may provide additional support for timely and clinically early diagnosis and intervention.

A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis.

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.

Disposable stainless steel working electrodes for sensitive and simultaneous detection of indole-3-acetic acid and salicylic acid in Arabidopsis thaliana leaves under biotic stresses.

The detection of phytohormones in real time has attracted increasing attention because of their critical roles in regulating the development and signaling of plants, especially in defense against biotic stresses. Herein, stainless steel sheet electrodes modified with carbon cement were coupled with paper-based analysis devices for direct and simultaneous detection of salicylic acid (SA) and indole-3-acetic acid (IAA) in plants. We demonstrated that the excellent conductivity of stainless steel sheet electrodes enabled us to simultaneously differentiate IAA and SA at a level of 10 nM. With our approach, the content of IAA and SA in Arabidopsis thaliana leaves infected or not infected with Pst DC3000 could be rapidly quantified at the same time. Our experimental results on differentiation of IAA and SA at different time points showed that there were antagonistic interactions between the IAA and SA after infection of Arabidopsis leaves with Pst DC3000. By offering a cost-effective approach for rapid and sensitive detection of IAA and SA, this study suggests that electrochemical detection can be used in the study and development of precision agriculture technology.

Interstitial lung disease in Primary Sjögren's syndrome.

BACKGROUND: Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren's syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. METHODS: Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. RESULTS: Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud's phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. CONCLUSIONS: Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud's phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.

Three-Dimensional Evaluation of the Postsurgical Stability of Mandibular Setback With the Surgery-First Approach: Comparison Between Patients With Symmetry and Asymmetry.

PURPOSE: The purpose of the present study was to evaluate the 3-dimensional postsurgical stability of mandibular setback with a surgery-first (SF) orthodontic treatment approach in patients with skeletal Class III malocclusions and facial asymmetry using cone-beam computed tomographic (CBCT) images. PATIENTS AND METHODS: Thirty-six patients who underwent mandibular setback with an SF approach for the correction of mandibular prognathism were enrolled in the present study. Patients were divided into symmetrical (n = 18) and asymmetrical (n = 18) groups according to their degree of menton deviation. CBCT images were acquired before surgery, 1, 6, and 12 months after surgery, and at the end of treatment. After reorienting of CBCT images using automatic volume-based registration, the position of the mandible at each time point was evaluated relative to its post-treatment position. MATLAB (MathWorks, Natick, MA) was used to represent all sequential changes in postoperative mandibular position. The increase in posterior vertical dimension at surgery was measured and then correlated with postsurgical mandibular stability. RESULTS: For up to 6 months after surgery, the position of the mandible differed considerably from its post-treatment position. At 12 months after surgery, the position of the mandible no longer differed substantially from its post-treatment position. The asymmetry group exhibited greater outward displacement of the proximal segment. The symmetrical and asymmetrical groups exhibited a positive correlation between postsurgical mandibular instability and the increase in posterior vertical dimension. CONCLUSION: These results indicate that mandibular position stabilizes 12 months after surgery performed with an SF approach. It is necessary to consider mandibular forward movement from the increase in posterior vertical dimension in surgical occlusion during the treatment planning stage. Moreover, clinicians should maintain the surgical position of proximal segments during postsurgical orthodontic treatment at least until 12 months after surgery.

Registration area and accuracy when integrating laser-scanned and maxillofacial cone-beam computed tomography images.

INTRODUCTION: The purpose of this study was to examine changes in registration accuracy after including occlusal surface and incisal edge areas in addition to the buccal surface when integrating laser-scanned and maxillofacial cone-beam computed tomography (CBCT) dental images. METHODS: CBCT scans and maxillary dental casts were obtained from 30 patients. Three methods were used to integrate the images: R1, only the buccal and labial surfaces were used; R2, the incisal edges of the anterior teeth and the buccal and distal marginal ridges of the second molars were used; and R3, labial surfaces, including incisal edges of anterior teeth, and buccal surfaces, including buccal and distal marginal ridges of the second molars, were used. Differences between the 2 images were evaluated by color-mapping methods and average surface distances by measuring the 3-dimensional Euclidean distances between the surface points on the 2 images. RESULTS: The R1 method showed more discrepancies between the laser-scanned and CBCT images than did the other methods. The R2 method did not show a significant difference in registration accuracy compared with the R3 method. CONCLUSIONS: The results of this study indicate that accuracy when integrating laser-scanned dental images into maxillofacial CBCT images can be increased by including occlusal surface and incisal edge areas as registration areas.

Reproducibility of an intraoral scanner: A comparison between in-vivo and ex-vivo scans.

INTRODUCTION: The purpose of this study was to assess the reproducibility of in-vivo and ex-vivo scans using an intraoral scanner. METHODS: Twenty adults with no missing teeth except for third molars were included in the study. Alginate impressions were taken, and plaster models were made from the impressions. Each subject underwent full-arch intraoral scanning twice with a TRIOS scanner (3Shape, Copenhagen, Denmark) at an interval of 2 weeks, and, the plaster models were scanned at the same interval with the same scanner. The first images of each scan were superimposed on the second scanned images using surface-based registration. In each case, the differences between the 2 scanned images were evaluated with color mapping. The reproducibility between the in-vivo and ex-vivo scans was compared using independent t tests and Bland-Altman analysis. RESULTS: The discrepancies between the first and second images were greater in the posterior than in the anterior regions for both the in-vivo and ex-vivo scans. Average surface differences between the first and second images were greater for the in-vivo scans (0.04 mm) than for the ex-vivo scans (0.02 mm). The Bland-Altman plots showed that the reproducibility of both scans was within the limits of agreement. CONCLUSIONS: The reproducibility of in-vivo scanning was comparable with ex-vivo scanning, although it showed a slight difference (0.02 mm) compared with ex-vivo scanning.

Easy-to-fabricate thin-film coating on PDMS substrate with super hydrophilicity and stability.

With the fast expansion of microfluidic applications, stable, and easy-to-fabricate PDMS surface coating with super hydrophilicity is highly desirable. In this study, we introduce a new kind of copolymer-based, single-layer thin-film coating for PDMS. The coating can exist in air at room temperature for at least 6 months without any noticeable deterioration in the super hydrophilicity (water contact angle ∼7°), resistance of protein adsorption, or inhibition of the EOF. In addition, this coating enables arbitrary patterning of cells on planar surfaces.

Screening, characterization and mechanism of a potential stabiliser for nisin nanoliposomes with high encapsulation efficiency.

The encapsulation efficiency (EE%) reflects the amount of bioactive components that can be loaded into nanoliposomes. Obtaining a suitable nanoliposome stabiliser may be the key to improving their EE%. In this study, three polyphenols were screened as stabilisers of nanoliposomes with high nisin EE%, with curcumin nanoliposomes (Cu-NLs) exhibiting the best performance (EE% = 95.94%). Characterizations of particle size, PDI and zeta potential indicate that the Cu-NLs had good uniformity and stability. TEM found that nisin accumulated at the edges of the Cu-NLs' phospholipid layer. DSC and FT-IR revealed that curcumin was involved in the formation of the phospholipid layer and altered its structure. FT-IR and molecular docking simulations indicate that the interactions between curcumin and nisin are mainly hydrogen bonding and hydrophobic. In whole milk, Cu-NLs effectively protected nisin activity. This study provides an effective strategy for improving the EE% of nanoliposomes loaded with nisin and other bacteriocins.

Microneedle electrochemical sensor based on disposable stainless-steel wire for real-time analysis of indole-3-acetic acid and salicylic acid in tomato leaves infected by Pst DC3000 in situ.

BACKGROUND: Indole-3-acetic acid (IAA) and salicylic acid (SA), pivotal regulators in plant growth, are integral to a variety of plant physiological activities. The ongoing and simultaneous monitoring of these hormones in vivo enhances our comprehension of their interactive and regulatory roles. Traditional detection methods, such as liquid chromatography-mass spectrometry, cannot obtain precise and immediate information on IAA and SA due to the complexity of sample processing. In contrast, the electrochemical detection method offers high sensitivity, rapid response times, and compactness, making it well-suited for in vivo or real-time detection applications. RESULTS: A microneedle electrochemical sensor system crafted from disposable stainless steel (SS) wire was specifically designed for the real-time assessment of IAA and SA in plant in situ. This sensor system included a SS wire (100 µm diameter) coated with carbon cement and multi-walled carbon nanotubes, a plain platinum wire (100 µm diameter), and an Ag/AgCl wire (100 µm diameter). Differential pulse voltammetry and amperometry were adopted for detecting SA and IAA within the range of 0.1-20 µM, respectively. This sensor was applied to track IAA and SA fluctuations in tomato leaves during PstDC3000 infection, offering continuous data. Observations indicated an uptick in SA levels following infection, while IAA production was suppressed. The newly developed disposable SS wire-based microneedle electrochemical sensor system is economical, suitable for mass production, and inflicts minimal damage during the monitoring of SA and IAA in plant tissues. SIGNIFICANCE: This disposable microneedle electrochemical sensor facilitates in vivo detection of IAA and SA in smaller plant tissues and allows for long-time monitoring of their concentrations, which not only propels research into the regulatory and interaction mechanisms of IAA and SA but also furnishes essential tools for advancing precision agriculture.

In Vivo Detection of Abscisic Acid in Tomato Leaves Based on a Disposable Stainless Steel Electrochemical Immunosensor.

Abscisic acid (ABA) plays an important regulatory role in plants. It is very critical to obtain the dynamic changes of ABA in situ for botanical research. Herein, coupled with paper-based analysis devices, electrochemical immunoelectrodes based on disposable stainless steels sheet were developed for ABA detection in plants in situ. The stainless steel sheets were modified with carbon cement, ferrocene-graphene oxide-multi walled carbon nanotubes nanocomposites, and ABA antibodies. The system can detect the ABA in the range of 1 nM to 100 µM, with a limit of detection of 100 pM. The ABA content in tomato leaves under high salinity was detected in situ. The trend of ABA changes was similar to the expression of SlNCED1 and SlNCED2. Overall, this study offers an approach for in situ detection of ABA in plants, which will help to study the regulation mechanism of ABA in plants and to promote the development of precision agriculture.

Multivesicular liposomes for sustained release of naltrexone hydrochloride: design, characterization and in vitro/in vivo evaluation.

Multivesicular liposomes containing naltrexone hydrochloride (DepoNTX) was prepared by using the traditional DepoFoam technology and the key formulation factors on encapsulation efficiency and particle size were investigated. A morphological characterization and in vitro/in vivo release assay was also carried out. NTX was successfully encapsulated in DepoNTX with good yield and showing the spherical, smooth and multivesicular characteristics of particle by a light microscope. The in vitro studies in human plasma and sodium chloride showed that 80-85% of NTX encapsulated in MVLs released slowly from particles over 5 days. In vivo study, after a single dose of 2.0 mg/kg of DepoNTX formulation administered subcutaneously in rats, plasma NTX levels were maintained at a relatively constant level above 10 ng/mL for approximately 120 h, while after administered NTX solution, NTX level was quickly decreased below 10 ng/mL within 20 h. The results of the study demonstrated that DepoNTX was very promising candidate for sustained release delivery of naltrexone hydrochloride.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

IMPORTANCE: The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

High through-put sequencing analysis of changes in oral flora in rats before and after zoledronate administration.

The aim of this study was to compare the changes in the oral flora of Sprague-Dawley rats before intraperitoneal injection of zoledronic acid, 6 weeks and 12 weeks after injection. Clinically, some antibiotics effectively treat patients with medicine-related osteonecrosis of the jaws (MRONJ), but the effect of broad-spectrum antibiotics for osteomyelitis of the jaw is not obvious. We therefore speculated that MRONJ may have some dominant bacteria. We used 12 healthy rats for the experiment. One rat was used for haematoxylin and eosin staining, three were used for gene analysis, three for signal molecule research, and five for 16SrDNA high-pass sequencing to compare the changes of flora before intraperitoneal injection of zoledronic acid, and 6 and 12 weeks after injection once every three days. Alpha and beta analysis was used for sequencing data. Analysis of the flora showed that the alpha diversity of the bacteria of rats injected with zoledronic acid was significantly higher than it was before injection (p < 0.05). At the phylum level, Bacteroidetes at 6 and 12 weeks of injection were significantly higher than those before injection (p < 0.05). At the genus level, the proportions of Novophingobium, Dubosiella, Mannheimia, Prevotella, Brevundimonas, and Bacteroides were higher than they were before injection (p < 0.05). The proportions of Lactobacillus, Mannheimia, Brevundimonas, Bacteroides, Roseovarius, Salegentibacter, Marinobacter, and Granulicatella in rats injected for 12 weeks were higher than those before injection (p < 0.05). Zoledronic acid can change the structure of oral flora in SD rats, in which Bacteroides increased and Actinomycetes decreased.

Analysis of the effect of zoledronic acid on gene differences in rat jaw.

BACKGROUND: With the widespread use of bisphosphonates, there are more and more complications about bisphosphonates, bisphosphonate-related osteonecrosis of the jaw is one.In the past ten years, there have been many studies on the mechanism of bisphosphonate associated jaw necrosis. OBJECTIVE: To investigate the influence and analysis of zoledronic acid on gene differences in rat jaw. METHODS: Six Sprague-Dawley female rats were randomly divided into control group (n = 3) and experimental group (n = 3). The experimental group received zoledronic acid injection for 12 weeks (dose of 0.2 mg / kg, 3 times a week).Control groups were injected with normal saline for 12 weeks. All rats were subjected to left mandibular first molar extraction 12 weeks later.After 8 weeks of tooth extraction, all rats were sacrificed and the mandible was removed.RNA-seq was used to analyze differential gene changes in all mandibles. Bioinformatics analysis of differential genes. RESULTS: Compared with the two rat groups, there were 2,830 different genes, including 1,001 upregulated genes and 1,829 down-regulated genes. Gene Ontology analysis revealed that the upregulated genes were mainly associated with immune-related pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that Hedgehog signaling pathway, Notch signaling pathway and Hippo signaling pathway were associated with upregulated genes. After the Gene Set Enrichment Analysis, the Gene Ontology analysis showed that 2559 / 6588 gene sets are upregulated in phenotype experimental group,and 342 gene sets with p <0.05. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that 95 / 316 gene sets are upregulated in phenotype experimental group, and four gene sets(Notch pathway, other types of O-glycan biosynthesis, ovarian steridogenesis and Hippo pathway) with p <0.05. CONCLUSIONS: Changes in differential genes are mainly related to immune-related processes and pathways, and pathways related to bone metabolism. The up-regulation of some genes can promote the progress of Bisphosphonate-related osteonecrosis of the jaw.

Disposable Stainless-Steel Wire-Based Electrochemical Microsensor for In Vivo Continuous Monitoring of Hydrogen Peroxide in Vein of Tomato Leaf.

As one of the pivotal signal molecules, hydrogen peroxide (H2O2) has been demonstrated to play important roles in many physiological processes of plants. Continuous monitoring of H2O2 in vivo could help understand its regulation mechanism more clearly. In this study, a disposable electrochemical microsensor for H2O2 was developed. This microsensor consists of three parts: low-cost stainless-steel wire with a diameter of 0.1 mm modified by gold nanoparticles (disposable working electrode), an untreated platinum wire with a diameter of 0.1 mm (counter electrode), and an Ag/AgCl wire with a diameter of 0.1 mm (reference electrode), respectively. The microsensor could detect H2O2 in levels from 10 to 1000 µM and exhibited excellent selectivity. On this basis, the dynamic change in H2O2 in the vein of tomato leaf under high salinity was continuously monitored in vivo. The results showed that the production of H2O2 could be induced by high salinity within two hours. This study suggests that the disposable electrochemical microsensor not only suits continuously detecting H2O2 in microscopic plant tissue in vivo but also reduces the damage to plants. Overall, our strategy will help to pave the foundation for further investigation of the generation, transportation, and elimination mechanism of H2O2 in plants.

The novel functions of ubiquitination in signaling.

Ubiquitin is best known for its function in targeting proteins for degradation by the proteasome. Recent studies have revealed several new functions of ubiquitin that are independent of proteasomal degradation. These functions include the novel signaling roles of ubiquitin in DNA repair and the activation of protein kinases such as IkappaB kinase. In both cases, a novel form of polyubiquitin chain linked through lysine-63 of ubiquitin plays an important regulatory role. Monoubiquitination also has signaling roles that are distinct from those of polyubiquitination, as illustrated from the studies of DNA repair. Thus, polyubiquitination and monoubiquitination have emerged as important signaling mechanisms that control diverse physiological and pathological processes.

[Clinical evaluation of oral midazolam sedation for dental treatment in children].

OBJECTIVE: To assess the safety, effectiveness and acceptability of oral midazolam sedation for dental treatment in children. METHODS: Twenty-three health children aged 4 to 14 (ASA I), who were classified as 4 or 5 by modified Venham's clinic anxiety and cooperative behavior rating scale, referred for dental treatment were included in the study. Each child was treated under sedation with oral midazolam (0.15-0.70 mg/kg), and totally 45 sedations were conducted. At each visit, heart rate, arterial oxygen saturation, respiration rate, sedation and behavioral scores were recorded. The level of acceptance and satisfaction of the patients and their guardians were recorded after the treatment. RESULTS: Among the 23 children, 19 were boys and 4 were girls with mean age of 6.2 years old. In all the 45 treatments, the heart rate, respiratory rate and arterial oxygen saturation levels were within acceptable clinical limits. Forty planned treatments were completed satisfactorily. Oral sedation was ineffective in 3 children, and they were treated under general anesthesia. Only 2 guardians refused to have oral midazolam sedation again. Six of seven children who had regular dental check-up could be treated under normal condition. CONCLUSION: Oral midazolam (0.15-0.70 mg/kg) could be a safe and acceptable approach of sedation for pediatric dental patients.

Condylar head remodeling compensating for condylar head displacement by orthognathic surgery.

The purpose of this study was to evaluate the association between kind of condylar displacement due to orthognathic surgery and the subsequent adaptive condylar head remodeling. The sample in this retrospective cohort study consisted of 30 patients (12 female and 18 male; mean age 22.7 y) with skeletal Class III malocclusion who underwent bilateral sagittal split ramus osteotomy (SSRO). Three-dimensional superimpositions of cone-beam computed tomography (CBCT) scan derived images from immediately after and 6 months after surgery were to reveal the type of remodeling, while images from before and immediately after surgery were to identify the type of condylar displacement. Laterally displaced condyles showed bone resorption on the lateral surfaces and deposition on the medial surfaces, whereas the contrary was found in medially displaced condyles. Anteriorly displaced condyles showed resorption on the anterior surfaces and deposition on the posterior surfaces, whereas the contrary was found in posteriorly displaced condyles. Superior surfaces of the condyles showed bone resorption regardless of displacement direction. The results indicate that condylar remodeling patterns (resorption/deposition) are determined by the direction of condylar displacement during surgery. However, condylar displacement by surgery is not completely compensated by condylar head remodeling, especially in case of downward displacement.

IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.