Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells.

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.

Furan-based fluorescent probe free radical capture membrane: Analysis of RO2 radical composition and transformation mechanism in urban atmosphere.

Peroxyl radicals (RO2) are important components of atmospheric radical cycling and generation, but their formation, distribution and evolution mechanisms in the atmospheric environment have not been investigated. In this paper, we propose a novel atmospheric RO2 radical trapping membrane that can trap low carbon number (Rc ≤ 5) RO2 radicals and identify their R-group structures by fluorescence spectroscopy and chromatography. We also analyzed the composition and evolution mechanism of RO2 species under different meteorological conditions in the atmospheric environment of Lanzhou, China, to provide scientific support for the treatment and research of atmospheric chemical pollution.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer. USP47 ablation compromised Treg homeostasis and function in vivo, resulting in the development of inflammatory disorders, and boosted antitumor immune responses. USP47 deficiency in Tregs triggered the accumulation of the c-Myc protein and in turn exacerbated hyperglycolysis. Mechanistically, USP47 prevented YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency. Our findings reveal that USP47 directs m6A-dependent metabolic programs to orchestrate Treg homeostasis and suggest novel approaches for selective immune modulation in cancer and autoimmune diseases by targeting of USP47.

Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses.

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8+ T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8+ T cells reveals that dietary fructose mediates attenuated transition of CD8+ T cells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8+ T cell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8+ T cell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ T cell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

Glycolysis drives STING signaling to facilitate dendritic cell antitumor function.

Activation of STING signaling in DCs promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark of activated DCs, but how the glycolytic pathway intersects with STING signaling in tumor-infiltrating DCs remains elusive. Here, we show that glycolysis drives STING signaling to facilitate DC-mediated antitumor immune responses. Tumor-infiltrating DCs exhibited elevated glycolysis, and blockade of glycolysis by DC-specific Ldha/Ldhb double deletion resulted in defective antitumor immunity. Mechanistically, glycolysis augmented ATP production to boost STING activation and STING-dependent DC antitumor functions. Moreover, DC-intrinsic STING activation accelerated HIF-1α-mediated glycolysis and established a positive feedback loop. Importantly, glycolysis facilitated STING-dependent DC activity in tissue samples from patients with non-small cell lung cancer. Our results provide mechanistic insight into how the crosstalk of glycolytic metabolism and STING signaling enhances DC antitumor activity and can be harnessed to improve cancer therapies.

Growth and intelligence development among a cohort of low birth weight infants / 中国学校卫生

Objective@#To explore growth and intelligence development of low birth weight infants (LBWI) at 24 and 36 months of age, so as to provide reference for early monitoring and intervention of the development of LBWI.@*Methods@#A total of 100 LBWI born and managed in Hefei Maternal and Child Health Care Institution were selected from 2012 October 1 to 2015 December 30, and 99 normal birth weight infants (NBWI) under child health management in the same sitinstitution were selected as controls. According a prospective cohort study method, and based on the establishment of a cohort and monitoring of childhood growth and development, a unified method was used to longitudinally follow up and observe the physical fitness of two groups of infants at the determined time points. The development of LBWI and NBWI at 24 and 36 months of age was surveyed using the Gesell Development Scale.@*Results@#Weight, length and head circumference of LBWI children at the age of 15-36 months were significantly lower than those of NBWI children ( P <0.05). In addition, 117 children (43.98%) completed the full assessment of intelligent development scale, including 62 LBWI and 55 NBWI. The scores of Gesell in NBWI group was higher than that in LBWI group at 24 and 36 months of age, including adaptability, gross motor, fine metor skills, language and personal social functions ( t =-4.17, -3.82, -3.21 , -3.03, -2.61; -4.23, -3.16, -3.07, -3.13, -3.99, P <0.05). Multivariate linear regression analysis found that birth weight was positively correlated with adaptability, gross motor, fine motor skills, language functions at 24 and 36 months of age and personal social function at 36 months of age ( β =0.004, 0.010; 0.003, 0.008; 0.003, 0.007; 0.004, 0.009; 0.011, P ＜0.05).@*Conclusion@#The growth and development of LBWI children are significantly delayed compared to NBWI children. The scores of LBWI children are lower than those of NBWI children in all functional areas. Weight is the main factor affecting children s intellectual development. Early monitoring and intervention of low birth weight infants should be carried out to avoid or mitigate adverse consequences.

Activation of the P2X7 receptor in the dental pulp tissue contributes to the pain in rats with acute pulpitis.

Treatment of acute pulpitis (AP) is beneficial for pain relief and pulp regeneration. The purinergic P2X7 receptor activation is responsible for the formation and maintenance of inflammation and pain. This study aims to determine the role of the pulp tissue P2X7 receptor to activate the mechanisms of the AP in rats. The Sprague-Dawley rats were divided into groups, namely, normal, normal saline (NS), and lipopolysaccharide (LPS) groups. Alterations in pain behavior were detected through head-withdrawal thresholds (HWTs), and the pathological changes in pulp tissue were studied through hematoxylin and eosin staining. The expression of the P2X7 receptor in pulp tissue was observed through immunohistochemistry and Western Blotting. The effect of the P2X7 receptor antagonist A-740003 on HWTs was also observed. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the pulp tissue of rats were analyzed through enzyme-linked immunosorbent assay. The HWTs were reduced in the rats with AP. Inflammation is formed but was found more severe in the LPS group than the NS group, and the expression levels of the P2X7 receptors in the NS and LPS groups were higher than in the normal group. The periodontal ligament injection of the A-740003 dose-dependant increases the HWTs in rats with AP. The IL-6 and TNF-α levels in the pulp in the NS and LPS groups were increased but reversed by A-740003 injection. In rats with AP, the expression level of the P2X7 receptor and IL-6/TNF-α release was upregulated. The A-740003 can relieve pain and reduce the inflammation progression in rats with AP.

Degradation of formaldehyde aqueous solution by Bi based catalyst and its activity evaluation.

Bi based catalysts have attracted continuous attention from the scientific community because of their excellent photochemical properties and wide application in photocatalytic treatment of environmental pollution. A series of Bi based catalysts with good crystallinity and high purity were prepared by calcination and hydrothermal synthesis. In the application of degrading formaldehyde aqueous solution in a mercury lamp and xenon lamp atmosphere, it was found that BiVO4 and Bi2WO6 showed excellent photochemical properties under ultraviolet and visible light. The tests of PL, UV-Vis and EIS confirmed their high activity. In the calculation based on density functional theory (DFT), through the analysis of the energy band structure, density of states (DOS) and partial wave density of states (PDOS), it is found that the d orbital of V and W elements has a great influence on the position and size of the energy band of the catalyst, which makes it have high activity and excellent electrochemical properties.

Phosphorylated PAMAM dendrimers: an analog of dentin non-collagenous proteins, enhancing the osteo/odontogenic differentiation of dental pulp stem cells.

OBJECTIVES: Polyamidoamine (PAMAM) dendrimers have well-defined structures, with monodispersity and easily modified surface groups, and they have broad applications in biomedicine. In this study, phosphorylated PAMAM (P-PAMAM) dendrimers were synthesized based on the idea of mimicking the phosphorylated proteins of dentin non-collagenous proteins (DNCP). Then, proliferation and osteo/odontogenic differentiation effects of P-PAMAM on dental pulp stem cells (DPSCs) were investigated and were compared with DNCP. MATERIALS AND METHODS: P-PAMAM was synthesized via the Mannich-type reaction. DNCP were extracted directly from human dentin with ethylenediaminetetraacetic acid (EDTA) solution. Then, the conditioned medium of P-PAMAM and DNCP were prepared respectively and applied to DPSCs. Proliferation of P-PAMAM was investigated with CCK-8, flow cytometry, and EdU test. Osteo/odontogenic differentiation of P-PAMAM was analyzed using alkaline phosphatase activity and staining, RT-PCR, western blot, alizarin red staining, and immunofluorescence staining. RESULTS: Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed that PAMAM were successfully phosphorylated. Western blot verified that the extracted DNCP contained dentin-related proteins DSPP, OPN, and BMP2. In cell proliferation, there was no apparent difference between P-PAMAM, DNCP, and Control groups (P > 0.05). P-PAMAM and DNCP upregulated related genes and proteins expression (DSPP/DSPP, COL-1/COL-1, ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN) and matrix mineralization. Still, the potential was lower than that of DNCP (P < 0.05). CONCLUSIONS: P-PAMAM dendrimers, as a biomimetic analog of DNCP, promote osteo/odontogenic differentiation of DPSCs without influencing their proliferation at a low concentration. CLINICAL RELEVANCE: This preliminary study about P-PAMAM dendrimers is expected to provide a more convenient bioactive macromolecular material for the regeneration of the pulp-dentin complex.

Worldwide Assessment of the Mandibular First Molar Second Distal Root and Root Canal: A Cross-sectional Study with Meta-analysis.

INTRODUCTION: This study assessed the prevalence of radix entomolaris and 2 canals at the distal aspect of mandibular first molars among different geographic regions by means of cone-beam computed tomographic imaging. METHODS: Precalibrated observers from 23 worldwide geographic locations followed a standardized screening protocol to assess 5750 cone-beam computed tomographic images of mandibular first molars (250 per region), gathering demographic data and recording the presence of radix entomolaris and a second canal at the distal aspect of teeth. Intra- and interrater reliability tests were conducted and comparisons among groups were performed using proportions and odds ratio forest plots. The significance level was set at 5%. RESULTS: The results of intra- and interrater tests were above 0.79. The prevalence of radix entomolaris varied from 0.9% in Venezuela (95% confidence interval [CI], 0%-1.9%) to 22.4% in China (95% CI, 17.2%-27.6%). Regarding the proportion of a second distal canal, it ranged from 16.4% in Venezuela (95% CI, 11.8%-21.0%) to 60.0% in Egypt (95% CI, 53.9%-66.1%). The East Asia subgroup was associated with a significantly higher prevalence of an extra distolingual root, whereas the American subgroup, the American native ethnic group, and elderly patients were linked to significantly lower percentages of a second canal at the distal aspect of teeth. No significant differences were noted between male or female patients. CONCLUSIONS: The overall worldwide prevalence rates of radix entomolaris and a second canal at the distal aspect of the mandibular first molar were 5.6% and 36.9%, respectively. The East Asia geographic region and Asian ethnic group had a higher prevalence of a second distal root.

Shaping ability of four single-file systems in the instrumentation of second mesiobuccal canals of three-dimensional printed maxillary first molars.

BACKGROUND: This study evaluated and compared the shaping ability of four advanced single-file nickel-titanium (NiTi) systems during the preparation of curved second mesiobuccal (MB2) canals in maxillary first molar replicas fabricated by three-dimensional (3D) printing via micro-computed tomography (Micro-CT) imaging. METHODS: A total of 60 3D-printed maxillary first molar replicas were constructed from one extracted tooth, with an angle of curvature ranging from 15° to 25°. The MB2 canals from these 60 replicas were divided into 4 groups of 15 replicas according to the canal instrumentation system used, namely, Waveone gold (WOG), Reciproc blue (RCB), XP-endo shaper (XPS) and M3-L. The specimens were scanned before and after preparation using Micro-CT. The pre- and post-instrumentation images of each specimen were superimposed, and the amount of resin removed, the change in surface area, the canal transportation, and centering ability were assessed using the Mimics software. Instrumentation time was also recorded. One-way analysis of variance and least significant difference (LSD) tests were used to statistically compare the groups. The significance level was set at 5%. RESULTS: Instrumentation time with M3-L was significantly longer than the other systems (P<0.05). The amount of resin removed and the change in surface area generated by the 4 systems were different at the apical, middle, and coronal thirds, and the total canal (P<0.05). Overall, WOG and XPS resulted in the less change than RCB and M3-L. There was no significant difference among the groups at the middle third regarding canal transportation and centering ability (P>0.05). However, a significant difference was found at the apical level (P<0.05), where RCB showed the poorest centering ability and the highest canal transportation (P<0.05). In addition, XPS resulted in the least canal transportation (P<0.05) at the coronal level, while there was no significant difference between the four groups in terms of centering ability. CONCLUSIONS: The M3-L instrument required more time to prepare the curved MB2 canals compared with the other systems. Overall, WOG and XPS showed the least resin removal and surface area change. M3-L, XPS, and WOG instruments respected the original canal curvature better than RCB files.

A Multidisciplinary Team Approach to the Treatment of Liver Cirrhosis.

OBJECTIVE: To explore the feasibility of treating cirrhosis using a multidisciplinary team approach (MDT) and to pinpoint the key factors influencing its implementation. METHODS: The data of 307 patients with decompensated cirrhosis were studied retrospectively. Patients who received more than two treatment measures were assigned to the MDT group (n=228), and patients who received symptomatic medical drug treatment only were assigned to the traditional treatment group (n=79). The follow-up period ranged from 4 to 10 years, and the average follow-up period was 5.7 years. The results of the biochemical tests for hepatitis B virus deoxyribonucleic acid, hepatitis C virus ribonucleic acid, and autoantibodies to liver disease were analyzed. RESULTS: The differences in gender and Child-Pugh grade of liver function between the two groups were not statistically significant. The MDT group had obvious advantages over the traditional treatment group in occupational composition, etiology composition, 5-year survival rate and annual hospitalization times. The leading causes of death in the MDT group, in descending order, were liver cancer, infection, mesenteric thrombosis, and non-hepatic disease, and, in the medical treatment group, they were liver failure, gastrointestinal bleeding, infection, and liver cancer. There was a significant statistical difference between the two groups (p < 0.05). In the multidisciplinary treatment, etiological treatment was the most widely used treatment, accounting for 79.8%, followed by endoscopic treatment (33.3%), peritoneal drainage and ascites reinfusion (25%), splenectomy combined with devascularization (11.4%) and stem cell transplantation and liver transplantation (1.8%). CONCLUSION: An MDT can improve the efficacy and prognosis of patients with cirrhosis and improve patient compliance. After multi-disciplinary intervention, the mortality spectrum of long-term survival patients with cirrhosis changes, and the mortality rate of liver cancer and non-liver disease increases.

ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells.

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91-governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer. T cell-specific deletion of Zfp91 in mice led to enhanced T cell proliferation and potentiated T cell antitumor function. Loss of ZFP91 increased mammalian target of rapamycin complex 1 (mTORC1) activity to drive T cell glycolysis. Mechanistically, T cell antigen receptor-dependent (TCR-dependent) ZFP91 cytosolic translocation promoted protein phosphatase 2A (PP2A) complex assembly, thereby restricting mTORC1-mediated metabolic reprogramming. Our results demonstrate that ZFP91 perturbs T cell metabolic and functional states in the TME and suggest that targeting ZFP91 may improve the efficacy of cancer immunotherapy.

Worldwide Prevalence of a Lingual Canal in Mandibular Premolars: A Multicenter Cross-sectional Study with Meta-analysis.

INTRODUCTION: The presence of multiple root canals is an important morphologic aspect of mandibular premolars. This study aimed to perform a worldwide analysis on the prevalence of a lingual canal in mandibular premolars and to evaluate its influence on patients' demographics in 23 countries using cone-beam computed tomographic images. METHODS: Observers from 23 countries were instructed to evaluate cone-beam computed tomographic images of 300 first and 300 second premolars (13,800 teeth) regarding the presence of a lingual canal, canal configuration, and data related to patients' ethnicity, age, and sex following a standardized screening methodology. Intra- and interrater evaluations were performed using the Cohen kappa test and intraclass correlation coefficient. Proportion and odds ratio forest plots were calculated in order to compare groups. Statistical significance was set at 5%. RESULTS: Both kappa and intraclass correlation coefficient values were above 0.60, and the percentage of agreement was 94.9% (first premolar) and 97.8% (second premolar). A significant statistical difference was observed between the worldwide proportion of a lingual canal in mandibular first (23.8%; range, 12.0%-32.7%) and second (5.3%; range, 1.0%-15.3%) premolars (P < .05). Asians and patients over 60 years old were associated with the lowest proportions of a lingual canal (P < .05), whereas Africans and younger groups were associated with the highest proportions (P < .05). The prevalence of a lingual canal in males (27.9%) was higher than females (20.0%) for the first premolar only (P < .05). Males were associated with 1.533 and 1.597 higher odds of presenting a lingual root canal in the first and second premolars, respectively. CONCLUSIONS: The worldwide proportion of a lingual root canal was 23.6% and 5.3% for the first and second premolars, respectively. Ethnicity, geographic region, age, and sex had an influence on the outcomes.

Analysis of second mesiobuccal root canal instrumentation in maxillary first molars with three nickel-titanium rotary instruments: a micro-computed tomographic study.

The aim of this study was to evaluate the shaping characteristics of Protaper Universal (PTU; Dentsply Tulsa Dental Specialties, Johnson City, TN), Hero Shaper (HS; MicroMega, Besacon, France) and Hyflex CM (HCM; Coltene-Whaledent, Allstetten, Switzerland) nickel-titanium systems with various apical sizes and tapers in second mesiobuccal (MB2) canal instrumentation using micro-computed tomographic imaging. A total of 27 maxillary first molars with independent patent MB2 canals were selected and randomly assigned to three groups according to the 3-dimensional morphologic aspects obtained from preoperative micro-computed tomographic scans. Canals were first negotiated with a size 8 K-file and finally prepared to F1, F2, and F3 with PTU and to sizes 20.04 taper, 25.04 taper, and 30.04 taper with HS and HCM. Postoperative scans were performed after each instrumentation with the same parameters used in the initial scan. The canal volume, canal transportation, untouched canal surface and wall thickness were measured and calculated using Mimics 10.01 software (Image Works, Materialise, Belgium). Statistical analysis was performed using one-way analysis of variance post hoc LSD tests. PTU removed more dentin than HS and HCM in all sections when instrumented to the same apical size (P < 0.05). HS and HCM presented a lower mean value of canal transportation than PTU in all measured sizes and sections. PTU presented a lower mean value of distal wall thickness than HS and HCM at the level of 1 and 2 mm below the furcation region in all measured sizes. In conclusion, for MB2 canal instrumentation, HS and HCM of 0.04 taper are safer than PTU.

Highly sensitive nucleic acid detection and transaminase level in treatment decisions for Chinese patients with cirrhosis caused by hepatitis.

OBJECTIVE: To explore the usefulness of highly sensitive nucleic acid detection for assisting with the accurate antiviral treatment of patients with cirrhosis that was caused by hepatitis. METHODS: There were 377 patients with hepatitis B with cirrhosis and 119 patients with hepatitis C with cirrhosis, either as hospitalized patients and outpatients, who were enrolled into the study. Among them, 299 were men and 197 were women between 23 and 82 years of age. All patients were examined using a domestic HBV DNA/HCV RNA test, which was negative in 162 cirrhosis with hepatitis B and 54 cirrhosis with hepatitis C patients (HBV DNA/HCV RNA <500 IU/mL). Prediction and analysis of the HBV DNA load using alanine aminotransferase (ALT) level was based on receiver operating characteristics (ROC) curve analysis. RESULTS: For patients with hepatitis C with cirrhosis, after the antiviral therapy, ALT, HCV RNA, and Child-Pugh grade were significantly improved compared with before treatment. ROC analysis results showed that an ALT level of 29 IU/mL was the most sensitive cutoff value to judge a positive HBV DNA load (sensitivity 1.0, specificity 0.237, Youden index 0.763). CONCLUSION: Precise detection for patients with cirrhosis caused by hepatitis is required for accurate therapy.

Postoperative outcomes after total hip arthroplasty in patients with Parkinson disease: A protocol of case control study.

BACKGROUND: Parkinson disease (PD) is a progressive neuromuscular disease associated with bradykinesia, tremor, and postural instability. We aimed to compare outcomes and complications of total hip arthroplasty (THA) between patients with PD and those without. METHODS: A single institution retrospective cohort from 2000 to 2018 was reviewed. PD patients were matched 1:2 with non-PD control patients for age, gender, American Society of Anesthesiologists score, and body mass index using a propensity score matching procedure. The primary outcome measures were postoperative complications and revision between PD and cohort groups. Secondary outcome measures were Harris Hip Score, hip range of motion, patient satisfaction, and surgery time. Univariable and multivariable logistic regression were used to determine the relationship between PD and surgical outcomes in the matched cohort. RESULTS: Using prospectively collated data, we identified 35 PD patients after primary THA. A control cohort of 70 primary THA patients was matched. CONCLUSION: Our hypothesis was that PD would have adverse impact on complication rates, range of movement, or improvement in functional outcome after subsequent THA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5446).

Microscopic removal of type III dens invaginatus and preparation of apical barrier with mineral trioxide aggregate in a maxillary lateral incisor: A case report and review of literature.

BACKGROUND: Invaginated teeth pose greater challenges in clinical management because of their complex configuration. With advancements in equipment and materials, such as the dental operation microscope, cone-beam computed tomography and mineral trioxide aggregate, the preservation rate of type III dens invaginatus could be greatly increased. CASE SUMMARY: This case report presented a 31-year-old woman with complaints of spontaneous swelling and pain in the right maxillary lateral tooth. With the aid of cone-beam computed tomography, type III dens invaginatus with apical periodontitis was diagnosed and confirmed. Three-visit endodontic treatment was performed. In the first visit, the invagination was carefully removed under the dental operation microscope, and chemomechanical preparation was done. In the second visit, mineral trioxide aggregate apical barrier surgery was performed in this tooth. In the third visit, the canal was finally obturated with thermoplastic gutta-percha to recover the crown morphology. A 26-mo follow-up revealed a satisfied outcome both in the radiographic and oral examinations. CONCLUSION: In this case, removal of the entire abnormal structure provided great convenience for the follow-up treatment. When confronted with the same clinical case in the future, we can take a similar approach to address it.

Nitrative Stress-Related Autophagic Insufficiency Participates in Hyperhomocysteinemia-Induced Renal Aging.

The kidneys are important organs that are susceptible to aging. Hyperhomocysteinemia (HHcy) is a risk factor for nephropathy and is associated with chronic nephritis, purpuric nephritis, and nephrotic syndrome. Numerous studies have shown that elevated serum homocysteine levels can damage the kidneys; however, the underlying mechanism of HHcy on kidney damage remains unclear. In this study, we make use of a diet-induced HHcy rat model and in vitro cell culture to explore the role of autophagy in HHcy-induced renal aging and further explored the underlying mechanism. We demonstrated that HHcy led to the development of renal aging. Promoted kidney aging and autophagic insufficiency were involved in HHcy-induced renal aging. HHcy decreased the expression of transcription factor EB (TFEB), the key transcription factor of autophagy-related genes in renal tissue. Further experiments showed that nitrative stress levels were increased in the kidney of HHcy rats. Interestingly, pretreatment with the peroxynitrite (ONOO-) scavenger FeTMPyP not only reduced the Hcy-induced nitrative stress in vitro but also partially attenuated the decrease in TFEB in both protein and mRNA levels. Moreover, our results indicated that HHcy reduced TFEB expression and inhibited TFEB-mediated autophagy activation by elevating nitrative stress. In conclusion, this study showed an important role of autophagic insufficiency in HHcy-induced renal aging, in which downregulation of TFEB plays a major role. Furthermore, downexpression of TFEB was associated with increased nitrative stress in HHcy. This study provides a novel insight into the mechanism and therapeutic strategy for renal aging.