Diagnosis and Treatment of Radioactive Iodine-Induced Sialadenitis: A 10-Year Endoscopic Experience.

OBJECTIVES: The aim of this study was to explore the endoscopic characteristics of radioactive iodine-induced sialadenitis (RAIS), and to evaluate the treatment outcomes of endoscopic intervention for RAIS. STUDY DESIGN: Retrospective case series. METHODS: Eighty-two consecutive patients (11 males and 71 females) diagnosed as RAIS from Nov. 2012 to Sep. 2023 were retrospectively included. All patients underwent endoscopic exploration and intervention of the affected glands. The endoscopic features were collected, and treatment outcomes were followed-up and evaluated through post to pre-operative comparisons of gland status. RESULTS: Overall, endoscopic procedures were undertaken for 162 parotid glands (PGs) and 62 submandibular glands (SMGs). Endoscopy showed severe lumen stricture (49.3%) and ductal atresia (23.5%) in PGs, as well as severe stenosis of the anterior duct and ectasia of the proximal duct (59.7%) in SMGs. During a median six months' follow-up, the treatment outcomes of PGs were evaluated as "improvement" in 23.4%，"lesion maintenance" in 45.1% and "lesion aggravation" in 31.5% of the glands. As for SMGs, the treatment outcomes were scored as "improvement"in 29.0%，"lesion maintenance"in 54.8%, and"lesion aggravation"in 16.1% of the glands. No significant differences of treatment outcomes were found relative to RAI treatment sessions and cumulative dosage. CONCLUSION: RAIS is characteristic of severe lumen stricture and ductal atresia in PGs, and stenosis of the distal duct and ectasia of the proximal duct in SMGs. Endoscopy can alleviate clinical symptoms of RAIS and help to preserve the gland function. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. RESULTS: Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. DISCUSSION AND CONCLUSION: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial.

Objective: To comprehensively evaluate the effect of acupuncture on gut microbiota, identify specific microbes closely related to the clinical efficacy of acupuncture, and explored the role of short-chain fatty acids (SCFAs). Methods: A randomized placebo-controlled trial was conducted with 80 FC patients and 28 healthy controls (HCs). FC patients randomly received 16 acupuncture (n = 40) or sham acupuncture (n = 40) sessions over 4 weeks; HCs received no treatment. The change in the proportion of patients with mean weekly complete spontaneous bowel movements (CSBMs) was considered as the primary outcome measure. Moreover, the composition and the predictive metabolic function of the gut microbiota from feceal samples were analyzed by 16S rRNA gene sequencing, while feceal SCFAs were identified via gas chromatography-mass spectrometry (GC-MS). Results: Compared to sham acupuncture, acupuncture significantly increased the proportion of CSBM responders, and improved spontaneous bowel movements (SBMs), straining, stool consistency, and quality of life. Moreover, Sequencing of 16S rRNA genes revealed that acupuncture improved ß-diversity and restored the composition of gut microbiota. Specifically, the abundance of beneficial bacteria such as g_Lactobacillus increased while that of pathogenic bacteria such as g_Pseudomonas decreased after acupuncture, which were significantly correlated with alleviated symptoms. Moreover, ten microbes including g_Coprobacter, g_Lactobacillus, and g_Eubacterium_coprostanoligenes_group might be considered acupuncture-specific microbes, and formed a stable interaction network. Additionally, GC-MS analysis indicated that acupuncture increased the content of butyrate acid in the gut, which was positively correlated with an increase in defecation frequency and a decrease in acupuncture-related pathogens. Finally, acupuncture specific-microbes including g_Coprobacter, g_Lactobacillus, g_Pseudomonas, g_Eubacterium_coprostanoligenes_group, g_Erysipelotrichaceae_UCG.003, g_Prevotellaceae_UCG.001, and g_Rolstonia could accurately predict the clinical efficacy of acupuncture (AUC = 0.918). Conclusion: Acupuncture could effectively improve clinical symptoms in FC patients, and was associated with gut microbiota reshaping and increased butyrate acid levels. Moreover, key microbial genera such as g_Coprobacter and g_Lactobacillus was predictive of acupuncture efficacy in treating FC. Future studies are required to validate the causal relationship between key microbial genera and acupuncture clinical efficacy, and should explore further metabolic pathways for designing personalized treatment strategies. Clinical Trial Registration: http://www.chictr.org.cn, Identifier: ChiCTR2100048831.

Confirmation of eosinophilic sialodochitis by terminal duct biopsy.

OBJECTIVE: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy. METHODS: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis. RESULTS: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis. CONCLUSION: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation.

[Regulation mechanism of resveratrol on odontogenic differentiation of human dental pulp stem cells].

PURPOSE: To investigate whether resveratrol promotes odontogenic differentiation of human dental pulp stem cells(DPSCs) by up-regulating the expression of silent information regulator 1 (SIRT1) and activating ß-catenin signaling pathway. METHODS: Different concentrations of resveratrol(0, 10, 15, 20 and 50 µmol/L) were used to treat DPSCs for 7 days and 14 days, and cell proliferative activity was detected by CCK-8. After odontogenic differentiation induced by 15 µmol/L resveratrol for 7 days, alkaline phosphatase(ALP) staining was performed and real-time quantitative reverse transcription PCR(qRT-PCR) was used to detect the mRNA expression of Runt-related transcription factor 2 (Runx2), dentin sialophosphoprotein(DSPP) and dentin matrix protein-1(DMP-1) in DPSCs. Western blot was used to detect the expression of SIRT1 in DPSCs on a specific day (0, 3rd, 5th, 7th and 14th) after differentiation induction. Western blot was also used to detect the expression of SIRT1 and activated ß-catenin during odontogenic differentiation of DPSCs treated by 15 µmol/L resveratrol for 7 days. The experimental data was analyzed with GraphPad Prism 9 software package. RESULTS: 15 µmol/L resveratrol had no significant effect on proliferation of DPSCs on the 7th and 14th day; 15 µmol/L resveratrol promoted odontogenic differentiation of DPSCs and up-regulated mRNA expression of RUNX2, DSPP, and DMP-1 in DPSCs; the expression of SIRT1 was the highest on the 7th day during odontogenic differentiation induction. Resveratrol resulted in the increasing protein expressions of SIRT1 and activated ß-catenin when DPSCs was induced to odontogenic differentiation for 7 days. CONCLUSIONS: Resveratrol promotes odontogenic differentiation of human DPSCs by up-regulating the expression of SIRT1 protein and activating ß-catenin signaling pathway.

Electroacupuncture for psychogenic erectile dysfunction: A resting-state functional magnetic resonance imaging study exploring the alteration of fractional amplitude of low frequency fluctuation.

Background: Psychogenic erectile dysfunction (PED) can seriously affect emotional and marital wellbeing. Electroacupuncture (EA) seems an effective method for treating PED. However, the central mechanisms underlying PED and the beneficial effects of EA treatment are unclear. The purpose of this study was to explore the central mechanisms of PED and to examine the impact of EA on erectile function. Methods: We recruited 14 PED patients and 14 matched normal controls (NCs). PED patients underwent twice rs-fMRI scans, respectively, pre- and post-treatment. The NCs only completed one rs-fMRI scan. We used the fractional amplitude of low frequency fluctuation (fALFF) to compare spontaneous neural activity between the PED patients and NCs, and to examine the differences between the pre- and post-EA treatment scans in the PED patients. Results: Scores on the IIEF5, QEQ, and SEAR improved after EA treatment. Compared with the NCs, PED patients showed increased fALFF in the right posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), right supplementary motor area (SMA), and left middle occipital gyrus. Most of these regions are closely implicated in sexual inhibition. The results of the correlation analysis results indicated that the fALFF of the right PCC was negatively correlated with IIEF5 scores. After treatment, fALFF values were substantially lower in the left triangular part of the inferior frontal gyrus, right DLPFC, right SMA, bilateral PCC and the orbital part of the middle frontal gyrus, and higher in the left middle temporal gyrus and left caudate nucleus. These regions mainly belong to the default mode network (DMN), executive control network and primary sensory motor network. The results of the correlation analysis indicated a positive association between the changes in IIEF5 score and changes in the fALFF value in the right PCC after EA treatment. Conclusion: In conclusion, our study highlights that PED patients have abnormal patterns of activity in the right PCC, right DLPFC, and right SMA mainly involved in the DMN, executive central network, and sensory motor network which could lead to a higher levels of sexual inhibition. EA might regulate the process of sexual inhibition to improve erection function in PED patients probably by modulating spontaneous brain activity in the DMN, executive central network, and sensory motor network.

Gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Regenerative endodontics represents a paradigm shift in dental pulp therapy for necrotic young permanent teeth. However, there are still challenges associated with attaining maximum root canal disinfection while supporting angiogenesis and preserving resident stem cells viability and differentiation capacity. Here, we developed a hydrogel system by incorporating antibiotic-eluting fiber-based microparticles in gelatin methacryloyl (GelMA) hydrogel to gather antimicrobial and angiogenic properties while prompting minimum cell toxicity. Minocycline (MINO) or clindamycin (CLIN) was introduced into a polymer solution and electrospun into fibers, which were further cryomilled to attain MINO- or CLIN-eluting fibrous microparticles. To obtain hydrogels with multi-therapeutic effects, MINO- or CLIN-eluting microparticles were suspended in GelMA at distinct concentrations. The engineered hydrogels demonstrated antibiotic-dependent swelling and degradability while inhibiting bacterial growth with minimum toxicity in dental-derived stem cells. Notably, compared to MINO, CLIN hydrogels enhanced the formation of capillary-like networks of endothelial cells in vitro and the presence of widespread vascularization with functioning blood vessels in vivo. Our data shed new light onto the clinical potential of antibiotic-eluting gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Hydrogels for Treatment of Different Degrees of Osteoarthritis.

Osteoarthritis (OA) is a common disease that severely restricts human activities and degrades the quality of life. Every year, millions of people worldwide are diagnosed with osteoarthritis, placing a heavy burden on society. Hydrogels, a polymeric material with good biocompatibility and biodegradability, are a novel approach for the treatment of osteoarthritis. In recent years, this approach has been widely studied with the development of materials science and tissue engineering technology. We reviewed the research progress of hydrogels in the treatment of osteoarthritis in the past 3 years. We summarized the required hydrogel properties and current applications according to the development and treatment of osteoarthritis. Furthermore, we listed the challenges of hydrogels for different types of osteoarthritis and presented prospects for future development.

Designing Triangular Silver Nanoplates with GSH/GSSG Surface Mixed States as Novel Nanoparticle-based Redox Mediators for Electrochemical Biosensing.

Herein, a dual signal-quenched electrochemical (EC) biosensing strategy utilizing surface-engineered trisodium citrate (TSC)-glutathione (GSH)/oxidized glutathione (GSSG)-capped triangular silver nanoplates (Tri-Ag NPsTSC-GSH/GSSG) as a novel nanoparticle-based redox mediator was explored for biomarker determination. In contrast with conventional redox mediators, Tri-Ag NPsTSC-GSH/GSSG provided more admirable EC performance along with a lower oxidation potential (∼0.14 V). Taking advantage of the split-type mode, the immune response in a 96-well microplate was independent from EC detection, which could effectively eliminate the biological interference and thereby greatly enhance the sensitivity. As for the surface engineering process of Tri-Ag NPs, it was composed of partial GSH replacement and the formation of the GSH/GSSG surface mixed state. Primarily, the signal response of Ag NPsTSC-GSH decreased due to the hindrance of GSH on electron transfer. Moreover, varying proportions of GSH/GSSG could further impede the oxidation process of Tri-Ag NPsTSC-GSH/GSSG and eventually realize efficient dual signal quenching of this system. Notably, the ZIF-67@MIL-88B-GOx nanocomposite as the label was applied for a cascade reaction system with GSH peroxidase-like activities to form the optimal GSH/GSSG proportion, causing sensitive changes in signal response with a range of different antigen concentrations. On this basis, the fabricated biosensor provided measurable outputs of aflatoxin B1 concentrations in a linear range of 0.0005-50 ng/mL with a low detection limit of 0.61 pg/mL (S/N = 3). All of the results indicated that the novel biosensor could be a promising analytical tool for future biomarker detection.

[Resveratrol suppressed the expression of MIP-2 induced by lipopolysaccharide in osteoblasts via up-regulating SOCS-3].

PURPOSE: To explore whether resveratrol dependents on the production of suppressor of cytokine signaling suppressor 3 (SOCS-3) in inhibiting mRNA production of macrophage inflammatory protein-2 (MIP-2) in osteoblasts induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e). METHODS: MC3T3-E1 cells were treated with different concentrations of resveratrol (0, 5, 10 and 20 µmol/L) and 20 µmol/L resveratrol for different time( 0, 10, 30, 60, 120 and 180 min). The expression of SOCS-3 protein was detected by Western blot. MC3T3-E1 cells were transfected with mouse SOCS3 siRNA (si-SOCS-3) and control siRNA(si-control). Reverse transcription real-time PCR(real-time RT-PCR) and Western blot was used to detect the silencing efficiency of SOCS-3. Cells were stimulated by 20 µg/mL P.e-LPS for 24 h after transfection, in the absence or presence of 20 µmol/L resveratrol for 1 h , and the changes of MIP-2 mRNA were determined by real-time RT-PCR. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: Treatment of MC3T3-El cells with different concentrations of resveratrol caused a significant increase in SOCS-3 protein expression in a dose-dependent manner. During the observation time of 180 min, SOCS-3 protein expression was the highest at 20 µmol/L resveratrol-treated osteoblasts for 60 min. The silencing efficiency of SOCS-3 mRNA was 63.7%. Transfection with SOCS-3 siRNA increased MIP-2 mRNA expression in LPS-stimulated MC3T3-E1 cells and negated the inhibitory effects of resveratrol on LPS-induced MIP-2 mRNA expression(P<0.05). CONCLUSIONS: Resveratrol inhibits the expression of MIP-2 mRNA in osteoblasts induced by P.e-LPS by up-regulating the expression of SOCS-3 protein.

Split-Type Electrochemical Immunoassay System Triggering Ascorbic Acid-Mediated Signal Magnification Based on a Controlled-Release Strategy.

This research put forward a novel split-type electrochemical (EC) immunosensor which integrated the controlled-release strategy with EC detection for application in the field of biosensing. Concretely, ascorbic acid (AA) was packaged in a cadmium sulfide (CdS)-capped spherical mesoporous bioactive glass (SBG) nanocarrier (SBGCdS) on account of encapsulation technology. To reduce the complexity of the bioanalysis, the detection antibody-labeled SBGCdS-AA bioconjugate was applied in a 96-well microplate for the immunoreaction process, which is independent of the EC determination procedure. Thus, the immune interference and steric hindrance caused by the accumulation of nanomaterials on the electrode could be minimized. Subsequently, AA was released efficiently via the destruction effect of dithiothreitol on the disulfide bond. In addition, for the as-prepared FcAI/l-Cys/gold nanoparticles (GNPs)/porous BiVO4 (p-BVO)/ITO EC sensing platform in the detection solution, the synergetic catalysis of Fc and GNPs/p-BVO toward the oxidation of the released AA could be realized, which triggered AA-mediated significant signal magnification throughout this study. In particular, p-BVO with an ordered nanoarray structure could accelerate the electron transfer to assist in sensitivity improvement of this system. This novel biosensor was capable of assaying the neuron-specific enolase (NSE) biomarker sensitively, from which a linear range of 0.001-100 ng/mL was derived along with a low detection limit of 1.08 pg/mL. An innovative way could be paved in the bioanalysis of NSE and other biomarkers.

Metformin-loaded nanospheres-laden photocrosslinkable gelatin hydrogel for bone tissue engineering.

The aim of this investigation was to engineer metformin (MF)-loaded mesoporous silica nanospheres (MSNs)-laden gelatin methacryloyl (GelMA) photocrosslinkable hydrogels and test their effects on the mechanical properties, swelling ratio, drug release, cytocompatibility, and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). As-received and carboxylated MSNs (MSNs-COOH) were characterized by scanning and transmission electron microscopies (SEM and TEM), as well as Fourier-transform infrared spectroscopy (FTIR) prior to hydrogel modification. MF-MSNs-COOH were obtained by loading MF into MSNs at a 1:1 mass ratio. Upon MSNs-COOH laden-hydrogels fabrication, the mechanical properties, swelling ratio and MF release were evaluated. SHEDs were seeded on the hydrogels and cytocompatibility was examined. The effects of the MF-MSNs-COOH/GelMA on the osteogenic differentiation of SHEDs were measured by ALP activity, Alizarin Red assay, and Real-time PCR. Statistics were performed using one-way ANOVA (α = 0.05). Morphological (SEM and TEM) analyses of pristine and carboxylated MSNs revealed a mean particle size of 200 nm and 218 nm, respectively. Importantly, an intrinsic nanoporous structure was noticed. Incorporation of MSNs-COOH at 1.5 mg/mL in GelMA led to the highest compressive modulus and swelling ratio. The addition of MSNs-COOH (up to 3 mg/mL) in GelMA did not impact cell viability. The presence of MF in MSNs-COOH/GelMA significantly promoted cell proliferation. Significant upregulation of osteogenic-related genes (except OCN) were seen for modified (MSNs-COOH and MF-MSNs-COOH) hydrogels when compared to GelMA. Altogether, the engineered MF-MSNs-COOH/GelMA shows great promise in craniomaxillofacial applications as an injectable, cell-free and bioactive therapeutics for bone regeneration.

Dual-Signaling Electrochemical Ratiometric Method for Competitive Immunoassay of CYFRA21-1 Based on Urchin-like Fe3O4@PDA-Ag and Ni3Si2O5(OH)4-Au Absorbed Methylene Blue Nanotubes.

A novel ratiometric electrochemical (EC) sensing platform was established for sensitive immunoassay of target cytokeratin 19 fragment 21-1 (CYFRA21-1) biomarker by combining competitive immunoreaction and multisignal output. This immunosensor utilized Ag nanoparticles (NPs)-functionalized urchin-like Fe3O4@polydopamine (u-Fe3O4@PDA-Ag) as a matrix to immobilize CYFRA21-1 antigens and methylene blue (MB)-absorbed Ni3Si2O5(OH)4-Au nanotubes (NTs) to label the anti-CYFRA21-1 (Ab). During the competitive immunoreaction, square wave voltammetric (SWV) current changes of Ag NPs from u-Fe3O4@PDA-Ag indicator and MB from Ni3Si2O5(OH)4-Au/MB indicator are relevant to the dosage of CYFRA21-1-acquired Ni3Si2O5(OH)4-Au/MB/Ab. More importantly, numerous CYFRA21-1 loaded stably on u-Fe3O4@PDA-Ag exhibited strong competitive capacity toward the target-CYFRA21-1 to combine Ni3Si2O5(OH)4-Au/MB/Ab, causing sensitive changes in the ratio of two measured SWV currents. Prominently, "ΔI = ΔIMB + |ΔIAg NPs|" (ΔIMB and |ΔIAg NPs| represents the change values of the oxidation peak currents of MB and Ag NPs, respectively) could be regarded as significantly amplifying the signal response and ultimately improving the sensitivity of CYFRA21-1 detection, from which we derived a wide dynamic range from 500 fg/mL to 50 ng/mL and a low detection limit of 0.39 pg/mL (S/N = 3). This work may exert a profound impact on monitoring other biomarkers in early diagnosis of diseases.

[Effect of resveratrol on the expression of MIP-2 in P.e-LPS-induced mouse osteoblasts].

PURPOSE: To investigate the effect of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) on the expression of macrophage inflammatory protein-2 (MIP-2) mRNA and protein levels in MC3T3-E1 cells and the influence of resveratrol on the expression of MIP-2 protein in P.e-LPS induced cells. METHODS: MC3T3-E1 cells were treated with different concentrations of P.e-LPS(0-50 mg/L) and 20 mg/L P.e-LPS for different time (0-48 h). The expression of MIP-2 mRNA and protein was detected by real-time RT-PCR and enzyme linked immunosorbent assay (ELISA). MC3T3-E1 cells were pretreated with resveratrol for 1 h in the presence of 20 mg/L P.e-LPS for 24 h，which was detected by ELISA. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: Treatment of MC3T3-El cells with different concentrations of P.e-LPS(0-50 mg/L) caused a significantly increase in MIP-2 mRNA and protein expression in dose-dependent manners.The expression of MIP-2 protein increased from (41.86±2.49) ng/L to (3126.74±158.30) ng/L, and the difference was significant(P<0.05). In the observation time (0-48 h), the impact of 20 mg/L P.e-LPS on induction of MIP-2 in MC3T3-El cells exhibited a time-dependent manner. At 48 h, the maximal induction of MIP-2 protein expression was (2102.55±123.27) ng/L(P<0.01). Incubation of cells with 10 µmol/L resveratrol for 1h significantly decreased the expression of MIP-2 protein from (1805.33±67.54) ng/L to（813.82±47.21) ng/L, and the difference was significant(P<0.05). CONCLUSIONS: The results suggest that P.e-LPS may mediate MIP-2 expression in MC3T3-E1 cells, and resveratrol has a significant inhibitory effect on this process.

Resveratrol Suppresses Matrix Metalloproteinase-2 Activation Induced by Lipopolysaccharide in Mouse Osteoblasts via Interactions with AMP-Activated Protein Kinase and Suppressor of Cytokine Signaling 1.

Porphyromonas endodontalis (P. endodontalis) lipopolysaccharide (LPS) is associated with the progression of bone resorption in periodontal and periapical diseases. Matrix metalloproteinase-2 (MMP-2) expression and activity are elevated in apical periodontitis and have been suggested to participate in bone resorption. Therefore, inhibiting MMP-2 activation may be considered a therapeutic strategy for treating apical periodontitis. Resveratrol is a natural non-flavonoid polyphenol that has been reported to have antioxidant, anti-cancer, and anti-inflammatory properties. However, the capacity of resveratrol to protect osteoblast cells from P. endodontalis LPS insults and the mechanism of its inhibitory effects on MMP-2 activation is poorly understood. Here, we demonstrate that cell viability is unchanged when 10 mg L-1P. endodontalis LPS is used, and MMP-2 expression is drastically induced by P. endodontalis LPS in a concentration- and time-dependent manner. Twenty micromolar resveratrol did not reduce MC3T3-E1 cell viability. Resveratrol increased AMP-activated protein kinase (AMPK) phosphorylation, and Compound C, a specific AMPK inhibitor, partially abolished the resveratrol-mediated phosphorylation of AMPK. In addition, AMPK inhibition blocked the effects of resveratrol on MMP-2 expression and activity in LPS-induced MC3T3-E1 cells. Treatment with resveratrol also induced suppressor of cytokine signaling 1 (SOCS1) expression in MC3T3-E1 cells. SOCS1 siRNA negated the inhibitory effects of resveratrol on LPS-induced MMP-2 production. Additionally, resveratrol-induced SOCS1 upregulation was reduced by treatment with compound C. These results demonstrate that AMPK and SOCS1 activation are important signaling events during resveratrol-mediated inhibition of MMP-2 production in response to LPS in MC3T3-E1 cells, and there is crosstalk between AMPK and SOCS1 signaling.

Short- and mid-term outcomes of robotic versus laparoscopic distal pancreatosplenectomy for pancreatic ductal adenocarcinoma: A retrospective propensity score-matched study.

BACKGROUND: Robotic distal pancreatectomy exhibits short-term benefits over laparoscopic distal pancreatectomy. The use of minimal invasive techniques to carry out distal pancreatosplenectomy (DPS) for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not gained popular acceptance. A comparative study was designed to analyze the short- and mid-term outcomes of robotic DPS (RDPS) versus laparoscopic DPS (LDPS) on patients with PDAC. METHODS: The baseline characteristics, perioperative outcomes and survival data among patients who underwent RDPS (n = 35) versus LDPS (n = 35) for PDAC between December 2011 and December 2015 were compared after a 1:1 propensity score matching. RESULTS: There were no significant differences in the operative time, blood loss, blood transfusion rate, and morbidity and pancreatic fistula rates between the RDPS and LDPS groups. RDPS significantly reduced the rate of conversion to laparotomy (5.7% vs. 22.9% when compared with LDPS, p = 0.04). There were no significant differences in R0 resection rates, number of harvested lymph nodes, positive to harvested lymph node ratios, and disease-free survival and overall survival rates between the two groups. A Cox proportional hazards analysis showed N1 stage to be significantly associated with worse survival and suggested that chemotherapy might prolong overall survival in these PDAC patients. CONCLUSIONS: This single-center study demonstrated that RDPS was safe and efficacious in treatment of PDAC. When compared with LDPS, RDPS was associated with a reduced rate of conversion to open surgery. There were no significantly differences in oncological outcomes and mid-term survival rates between the groups of patients who underwent RDPS or LDPS.

A Clinical Observation of Functional Abdominal Pain Syndrome in Patients Treated by Traditional Chinese Spinal Orthopedic Manipulation.

OBJECTIVE: To evaluate the clinical effect of traditional Chinese spinal orthopedic manipulation (TCSOM) in treating patients with functional abdominal pain syndrome (FAPS) in comparison with Pinaverium Bromide (Dicetel, PBD), and to assess a possible cause for FAPS. METHODS: Eighty patients with FAPS were randomly and equally assigned to the TCSOM group and PBD group according to the random number table. All patients in the TCSOM group were treated with a maximum of 5 times of spinal manipulations. Patients in the PBD group were instructed to take 50 mg 3 times a day, consistently for 2 weeks. The symptoms of pre- and post-treatment were assessed on a visual analog scale (VAS) pain score. A symptom improvement rating (SIR) was implemented to evaluate the effects of the treatments. RESULTS: The symptoms of 27 cases of the TCSOM group were relieved soon after the first TCSOM treatment and 9 cases were significantly improved. The VAS pain scores in the TCSOM group were significantly lower than those in the PBD group after 2 weeks treatment. According to the SIR based on VAS, the TCSOM group included 30 cases with excellent results, 7 cases with good, and 3 cases with poor. Adverse events to the treatment were not reported. Based on VAS, the PBD group reported 8 cases with excellent results, 10 cases with good and 22 cases with poor. There was a significant difference between the two groups (P<0.01). CONCLUSIONS: The displacement of intervertebral discs and/or vertebra in the thoracic or lumbar region seems to be a contributing factor in the symptoms of FAPS. TCSOM is an effective treatment for FAPS.

Insulin-like growth factor-1 promotes the proliferation and odontoblastic differentiation of human dental pulp cells under high glucose conditions.

Insulin-like growth factor-1 (IGF-1) promotes human dental pulp stem cell proliferation and osteogenic differentiation. However, the effects of IGF-1 on the proliferation, apoptosis and odontoblastic differentiation (mineralization) of dental pulp cells (DPCs) under high glucose (GLU) conditions remain unclear. In this study, isolated primary human DPCs were treated with various concentrations of high GLU. Cell proliferation and apoptosis were determined by Cell Counting Kit-8 and Annexin V-FITC/PI assays, respectively. The cells were cultured in odontoblastic induction medium containing various concentrations of high GLU. Odontoblastic differentiation was determined by alkaline phosphatase (ALP) activity assay. Mineralization formation was evaluated by von Kossa staining. The expression levels of IGF family members were measured by western blot analysis and RT-qPCR during proliferation and differentiation. The cells were then exposed to 25 mM GLU and various concentrations of IGF-1. Cell proliferation, apoptosis, ALP activity, mineralization formation and the levels of mineralization-related proteins were then evaluated. Our results revealed that high GLU significantly inhibited cell proliferation and promoted cell apoptosis. GLU (25 and 50 mM) markedly reduced ALP activity and mineralization on days 7 and 14 after differentiation. The levels of IGF family members were markedly decreased by high GLU during proliferation and differentiation. However, IGF-1 significantly reversed the effects of high GLU on cell proliferation and apoptosis. Additionally, IGF-1 markedly restored the reduction of ALP activity and mineralization induced by high GLU. Our findings thus indicate that IGF-1 attenuates the high GLU-induced inhibition of DPC proliferation, differentiation and mineralization.

Sirtuin 1 regulates matrix metalloproteinase-13 expression induced by Porphyromonas endodontalis lipopolysaccharide via targeting nuclear factor-κB in osteoblasts.

Porphyromonas endodontalis lipopolysaccharide (P.e LPS) is an important initiating factor for periapical inflammation and bone destruction. Matrix metalloproteinase-13 (MMP-13) has been shown to participate in the formation and diffusion of periapical bone lesion in chronic apical periodontitis. Sirtuin 1 (SIRT1) is a key regulator of inflammation in mammalian cells which suppresses the release of inflammatory mediators. This study aimed to explore the role of SIRT1 in regulating MMP-13 expression induced by P.e LPS in osteoblasts. P.e LPS stimulated MMP-13 expression in MC3T3-E1 cells. Knockdown of SIRT1 reinforced the increase of MMP-13mRNA expression induced by P.e LPS. SIRT1 activator resveratrol significantly reduced the expression of MMP-13 and SIRT1 inhibitor EX-527 enhanced the expression of MMP-13. Moreover, SIRT1 activation with resveratrol inhibited acetylation of NF-κB p65 and NF-κB transcriptional activity, which were enhanced by P.e LPS. In addition, NF-κB p65 was involved in P.e LPS-induced MMP-13 expression via directly binding to the MMP-13 promoter. However, SIRT1 activation significantly interfered with this binding. These findings strongly suggest that P.e LPS induces MMP-13 expression in osteoblasts, and SIRT1 suppresses this expression of MMP-13 through targeting NF-κB p65. This provides new insights into understanding the actions of SIRT1 on anti-inflammatory and anti-bone resorption activity.

[Mechanism of TNF-α in bone defect of chronic apical periodontitis].

PURPOSE: To investigate the effect of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) on the expression of tumor necrosis factor-α(TNF-α) mRNA in MC3T3-E1 cells and the role of NF-κB signaling on the expression of macrophage colony stimulating factor (M-CSF) induced by TNF-α in MC3T3-El cells． METHODS: MC3T3-E1 cells were treated with different concentrations of P.e-LPS(0-50 mg/L) and 10 mg/L P.e-LPS for different time (0-24 h). The expression of TNF-α mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR). MC3T3-E1 cells were treated with different concentrations of TNF-α(0-10 ng/L) for 6 h. The expression of M-CSF mRNA and protein was detected by RT-PCR and enzyme-linked immunoadsordent assay(ELISA).The expression of M-CSF protein was also detected in 10 ng/L TNF-α treated MC3T3-E1 cells after pretreated with BAY 11-7082 for 1 h, a special NF-κB inhibitor . Statistical analysis was performed using Multi-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: The level of TNF-α mRNA increased significantly after treatment with different concentrations of P.e-LPS(0-50 mg/L)，which indicated that P.e-LPS induced osteoblasts to express TNF-α mRNA in dose dependent manners. Maximal induction of TNF-α mRNA expression was seen in the MC3T3-E1 cells treated with 10 mg/L P.e-LPS for 6 h. After 6 h, the expression of TNF-α mRNA decreased gradually .The expression of M-CSF mRNA and protein was increased in a does- dependent manner by different concentrations of TNF-α treatment（0-10 ng/L）. The expression of M-CSF protein increased from (37±2) ng/L(control group) to (301±8) ng/L(10 ng/L group).The protein of M-CSF decreased significantly after pretreatment with 10 µmol/L BAY 11-7082 for 1 h, and the expression of M-CSF proteins was reduced from (253±14) ng/L to (154±2) ng/L .BAY group had no significant difference from the control group. CONCLUSIONS: The expression of TNF-α mRNA was increased by P. endodontalis LPS treatment in osteoblast. TNF-α may induce the expression of M-CSF in MC3T3-E1 cells through the signaling of NF-κB. It suggests that TNF-α affect osteoblasts through autocrine way for bone destruction in chronic apical periodontitis induced by P.e-LPS.