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The virtual articulator is a tool that reproduces the relationship between the jaws in a virtual environment. The purpose of this clinical report was to describe a completely digital protocol starting from the virtual articulator mounting to developing static and dynamic occlusion in a complex prosthetic rehabilitation.

Background Type 2 diabetes (T2D) is aglobal health burden that accounts for about 90% of all cases of diabetes. Injury to the kidneys is aserious complication of type 2 diabetes. Maackiain, apterocarpan extracted from roots of Sophora flavescens, has been traditionally used for various disease conditions. However, nothing is known about its possible potential effect on HFD/STZ-T2D-induced nephrotoxicity. Methods In this study, T2D rat model is created by high-fat diet (HFD) for 2 weeks with injection of asingle dose of streptozotocin (35mg/kg body weight). T2D rats were orally administered with maackiain (10 and 20mg/kg body weight) for 7 weeks. Results Maackiain suppressed T2D-induced alterations in metabolic parameters, lipid profile and kidney functionality markers. By administering 10 and 20mg/kg maackiain to T2D rats, it was able to reduce lipid peroxidation while improving antioxidant levels (SOD, CAT, and GSH). Furthermore, the present study demonstrated the molecular mechanisms through which maackiain attenuated T2D-induced oxidative stress (mRNA: Nrf2, Nqo-1, Ho-1, Gclc and Gpx-1; protein: NRF2, NQO-1, HO-1 and NOX-4), inflammation (mRNA: Tlr, Myd88, IκBα, Mcp-1, Tgf-β, col4, Icam1, Vcam1 and E-selectin; Protein: TLR4, MYD88, NF-κB, IκBα, MCP-1; levels: TNF-α and MCP-1) and apoptosis (mRNA: Bcl-2, Bax, Bad, Apaf-1, Caspase-9 and Caspase-3; protein: Bcl-2, Bax, Caspase-3 and Caspase-9) mediated renal injury. Additionally, significant improvement in kidney architecture was observed after treatment of diabetic rats with 10 or 20mg/kg maackiain. Conclusion Maackiain protects the kidney by decreasing oxidative stress, inflammation, and apoptosis to preserve normal renal function in type 2 diabetes., Graphical Abstract

Endometrial cancer (EC) is one of the most common gynecological tumors. The first-line treatment for advanced EC is chemoradiotherapy. However, patients in poor health, such as those with intestinal obstruction, have limited tolerance for the side effects of chemoradiotherapy. Individualized precision treatment may bring new hope to these patients. Herein, we have reported on a 56-year-old female patient with metastatic EC combined with severe intestinal obstruction. Due to her inability to tolerate needle biopsy and standard treatment protocols, next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) testing was performed and PTEN deletion was found. Following, the patient commenced everolimus (10 mg, qd) treatment and partial shrinkage of metastases was observed one month later. Then, everolimus (10 mg, qd) plus carboplatin (100 mg d1, 8, 15, q28d) for 2 cycles, everolimus (10 mg, qd) plus carboplatin (200 mg d1, 8, q21d) for 2 cycles, and everolimus (10 mg, qd) plus carboplatin (200 mg d1, 2, q21d) for 2 cycles were performed, and the patient got partial response for 10 months. From June 2019, the patient continued to benefit from everolimus and subsequently experienced continued benefit for more than 12 months. This is the first reported case of an EC patient who benefited from everolimus as a first-line treatment based on PTEN deletion. This case provides important clinical experience for the precision treatment of patients with advanced EC.

Background As a major virus outbreak in the twenty-first century, the coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented hazards to mental health globally. Methods We performed a cross-sectional study based on the results of an online survey. The survey was conducted 1 month after the outbreak (February 18–29, 2020) and repeated at the time of resuming activity (April 8–14, 2020). The 15-item Death Anxiety Scale (T-DAS) was used to assess the degree of death anxiety, and the Chinese version of PTSD checklist-civilian version (PCL-C), for PTSD symptom clusters. Through convenient sampling, a total of 7678 cases were collected. Results Our findings showed that even after the lockdown was lifted, the prevalence of the symptoms of post-traumatic stress disorder (PTSD) and death anxiety remained significantly high in the general population affected by the outbreak. Regression model analysis showed that PTSD was significantly associated with age > 50 years, contact history/living community, poor health status of participants, past traumatic experience (PTE), and medical occupation. Moreover, death anxiety mediated the relationship between life-threatening PTE and PTSD, indicating that reducing death anxiety could buffer the negative effects of PTE on PTSD. Conclusions Despite the lifting of the lockdown, long-term adverse psychological effects remain in the affected general population. The management of mental health after major public health events is important, and high-risk groups such as the elderly and healthcare workers should receive targeted interventions. In addition, the study suggests that methods for alleviating death anxiety must be included in plans to manage the psychological impact of public health emergencies.

Purpose To evaluate the accuracy of static computer-assisted implant surgery (sCAIS) for tooth-supported free-end dental implantation with the aid/and without the aid of fixation pins to secure the surgical template through comparison between planned, 3D printed guide position and placement implant position. Materials and methods Thirty-two duplicated maxillary resin models were used in the present in vitro study. Digital planning was performed and fabrication of a surgical template that allowed implant placement on the distal extension edentulous site of the model (maxillary left side). A first optical scan was performed after fitting the surgical template on the model to assess the deviation at the surgical guide level. After placing implants in the model using the surgical guide, scan bodies were attached to the implants, and a second scan was performed to record the position of placed implants. The digital representations were later superimposed to the pre-operative scan and measurements of implant deviations were performed. Global (coronal and apical), horizontal (coronal and apical), depth and angular deviations were recorded between planned implant position, guide position and placement implant position. Three-way ANOVA was used to compare implant location (#13, 14 and 15), fixation pin (with or without pin) and guide comparison (planned, guided and placement). Results Final implant placement based on the digital plan and based on the 3D printed guide were very similar except for depth deviation. Use of fixation pin had a statistically significant effect on the depth and angular deviation. Overall, without fixation pins and based on guide vs. placement, mean global coronal (0.88 ± 0.36 mm), horizontal coronal (0.55 ± 0.32 mm) and apical (1.44 ± 0.75 mm), and angular deviations (4.28 ± 2.01°) were similar to deviations with fixation pins: mean global coronal (0.88 ± 0.36 mm); horizontal coronal (0.67 ± 0.22 mm) and apical (1.60 ± 0.69 mm); and angular deviations (4.53 ± 2.04°). Horizontal apical without pins (1.63 ± 0.69 mm) and with fixation pins (1.72 ± 0.70 mm) was statistically significant (p = 0.044). Depth deviation without pins (-0.5 ± 0.5 mm) and with fixation pins (-0.16 ± 0.62 mm) was also statistically significant (p = 0.005). Further analysis demonstrated that the final sleeve position on the 3D printed guide was on average 0.5mm more coronal than the digital plan. Conclusions The use of surgical guides with or without fixation pins can provide clinically acceptable outcomes in terms of accuracy in implant position. There was a statistically significant difference in the accuracy of implant position when utilizing fixation pins only for horizontal apical and depth deviation. Additionally, a statistically significant difference between the planned and the 3D printed surgical guide when considering the sleeve position was detected. This article is protected by copyright. All rights reserved.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD., Graphical abstract Image 1, Highlights • GBDP is composed of 46 constituents. • Content of 12 constituents were different between GBDP and EGb 761. • GBDP attenuated neurological deficits in zebrafish and mice PD models. • GBDP prevented PD through anti-apoptosis and Akt/GSK3β signaling pathways. • GBDP might be a potential therapeutic agent for PD.

There was no optimal risk assessment tool to stratify the risk of peripherally inserted central catheter-related venous thromboembolism (PICC-RVT) in cancer patients. We currently use the Caprini risk assessment model for thrombotic risk assessment, but no evidence exists on the effectiveness of Caprini in such patients. This study was to assess the validity of the Caprini in Chinese cancer patients with PICCs. We conducted a prospective study of 468 participants. Following calculating the Caprini score, color Doppler ultrasonography was performed every 7 days for 3 weeks to confirm PICC-RVT. There was a correlation between PICC-RVT and the Caprini score. Compared with scores of 5, the risk was 2.089-fold greater (95% CI 1.165–3.743, P = 0.012) in patients with a score of 6 and 7, and 7.156-fold greater (95% CI 3.157–16.217, P < 0.001) in patients with scores ≥8. The area under the receiver-operating characteristic curve was 0.636 (95% CI 0.590–0.680; P < 0.001). 6 was the best cutoff point for Caprini, with a sensitivity of 0.76 and a specificity of 0.44. The Caprini can be used for high-risk screening of the PICC-RVT in cancer patients, and classification of the highest risk level using a score of 6 can be more clinically significant compared to 5 as recommended. The results provide evidence for the practitioner's early use of the Caprini to assess the thrombotic risk in patients with PICCs and take timely prevention measures. But pharmacological prevention should be considered seriously for its low specificity.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p

Vanadium is an important trace element in bone and is involved in bone metabolism, bone formation, and bone growth, but the roles of various vanadium ions, especially of pentavalent vanadium, in bone tissue regenerative repair have been underestimated and even misinterpreted for a long time. The main purposes of this study are to investigate the release profile of Si, Ca, P, and V ions from vanadium doped mesoporous bioactive glass (V-MBG) particles and to explore the effect of pentavalent vanadium ions on proliferation and osteogenic differentiation of BMSCs as well as the corresponding osteogenic signaling pathway. On the basis of preparations of V-MBG particles with different pentavalent vanadium contents, the ion release behavior from V-MBG in distilled water and simulated body fluid was systemically investigated. Furthermore, the cytocompatibility and osteogenic effect of V-MBG extracts were studied in rBMSCs, and the related molecular mechanisms were preliminarily discussed. The results of dissolution experiments showed that the V ionic concentration exhibited a burst increase and then a sustained slow increase in the two media. The resultant V ions from 1.0V-MBG, 4.0V-MBG and 10.0V-MBG at 21 days were about 1.1, 5.8, and 12.5 mg L-1 in water, respectively, and 1.6, 4.8 and 12.8 mg L-1 in SBF, respectively. The release behaviors of Si, Ca, P, and V ions were evidently affected by high contents of incorporated vanadium. The cellular results indicated that compared to the control and MBG groups, the V(V) ions in V-MBG extracts at about 19.4 μM markedly promoted the proliferation, the gene and protein expression of BMP-2 and COL-I, and the ALP activity of rBMSCs in non-osteoinductive media, but insignificantly stimulated the OCN protein synthesis. More deeply, V(V) ions at about 19.4 μM significantly upregulated the gene and protein expressions of Itga 2b, FAK, and pERK1/2, demonstrating that V(V) ions could regulate osteogenic differentiation of rBMSCs through the activation of the Itga 2b-FAK-MAPK (pERK1/2) signaling pathway. The in vivo results further confirmed that V-MBG induced and promoted new bone formation in the defect area compared to the PGC and PGC/V-M0 groups. These results would contribute to modify the perception about the biocompatibility and osteogenic promotion of pentavalent vanadium at an appropriate concentration.

Since December 2019, when coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan and then spread worldwide, there have been ...

Bacterial infection has become an urgent health problem in the world. Especially, the evolving resistance of bacteria to antibiotics makes the issue more challenging, and thus new treatments to fight these infections are needed. Antibacterial photodynamic therapy (aPDT) is recognized as a novel and promising method to inactivate a wide range of bacteria with few possibilities to develop drug resistance. However, the photosensitizers (PSs) are not effective against Gram-negative bacteria in many cases. Herein, we use conjugated meso-tetra(4-carboxyphenyl)porphine (TCPP) and triaminoguanidinium chloride (TG) to construct self-assembled cationic TCPP-TG nanoparticles (NPs) for efficient bacterial inactivation under visible light illumination. The TCPP-TG NPs can rapidly adhere to both Gram-negative and Gram-positive bacteria and display promoted singlet oxygen (1O2) generation compared with TCPP under light irradiation. The high local positive charge density of TCPP-TG NPs facilitates the interaction between the NPs and bacteria. Consequently, the TCPP-TG NPs produce an elevated concentration of local 1O2 under light irradiation, resulting in an extraordinarily high antibacterial efficiency (99.9999% inactivation of the representative bacteria within 4 min). Furthermore, the TCPP-TG NPs show excellent water dispersity and stability during 4 months of storage. Therefore, the rationally designed TCPP-TG NPs are a promising antibacterial agent for effective aPDT.

Antimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for the treatment of bacterial infections, which inactivates a broad spectrum of bacteria. However, many traditional photosensitizers (PSs) are hydrophobic with poor water solubility and easy aggregation. On the other hand, some light sources such as ultraviolet (UV) have poor penetration and high cytotoxicity. Both issues lead to undesired photodynamic therapy efficacy. To overcome these issues, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei. Sorbicillinoids could effectively generate singlet oxygen (1O2) under UV light irradiation and ultimately display photoinactivation activity on Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus but not Gram-negative ones such as Escherichia coli and Proteus vulgaris. Sorbicillinoids were found to enter S. aureus but not E. coli. S. aureus treated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semipermeability without overt cell membrane disruption, none of which was found in the treated E. coli. All these contribute to the sorbicillinoid-based photoinactivation of Gram-positive bacteria. Moreover, the dark toxicity and phototoxicity on mammalian cells or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility. This study expands the utilization of UV light for surface sterilization to disinfection in solution. Therefore, sorbicillinoids, a type of secondary metabolite from fungus, have a promising future as a new PS for APDT using a nontoxic dose of UV irradiation.

Objective This article describes a digital dental esthetic ceramic veneer treatment workflow using a stereolithographic template for teeth preparation. Clinical considerations We have presented the case of a 33-year-old woman with dental fluorosis who wanted an esthetic ceramic veneer treatment. A digital smile design was created on a virtual patient, and a virtual diagnostic wax-up was made. Based on the suggested ceramic material thickness, virtual teeth preparation was performed on the diagnostic wax-up. A special-teeth preparation template was then created digitally and fabricated using a stereolithographic technique. This template guided the teeth preparation using a special bur with a stopper. The veneers were fabricated by CAD/CAM and delivered good esthetics and function. Conclusions The stereolithographic tooth reduction template helps realize digital restorative planning. It provides better control of the reduction depth of the labial and incisal preparation, making the operation simpler. Clinical significance The digital dental esthetic ceramic veneer treatment workflow described here using a stereolithographic template for teeth preparation helped with the accurate control of reduction depth for minimally invasive teeth preparation, making the operation simpler, which is a significant improvement over the previous methods.

To enhance the precision manufacturing of microstructures, a 3-D isotropic microprobe based on three-flexible-hinge suspension and orthogonal microball collimation was developed. First, the sensing principle of the microprobe was investigated by analyzing its displacement transfer principle and the displacement measurement principle of the orthogonal microball collimation optical paths. Second, the stiffness model of the microprobe at the tip was established by considering the influence of the measuring stylus stiffness. Subsequently, the isotropic design of the microprobe was developed in terms of the 3-D isotropic stiffness and sensitivity. Utilizing the rotation and translation of the three-flexible-hinge suspension, the 3-D tip displacements were transformed into the 3-D displacements of the microball of the transfer stylus which was fixed in the reverse coaxial direction to the measuring stylus, then the 3-D displacements of the microball were transformed into centroid position shifts of the light spots by the orthogonal microball collimation optical paths. Finally, a 3-D isotropic microprobe was fabricated, and experiments to verify its performance for measurements pertaining to microholes and microsteps were conducted. A method for the effective measurement of microholes was established, which could improve the measurement efficiency, and the tilt angle of the countertop was considered for the measurement of the microsteps. The experimental results indicated that the proposed microprobe could help realize low measurement force, 3-D isotropic measurement of microstructures, and improvement of the measurement accuracy.

Purpose: To evaluate the effects of passive music therapy on anxiety and vital signs among lung cancer patients at their first peripherally inserted central catheter placement procedure in China. Methods: A randomized controlled clinical trial was conducted in the cancer center of a hospital in Chengdu from May to December 2017. A total of 304 lung cancer patients who met the inclusion and exclusion criteria were recruited and randomly assigned to experimental ( n = 152) and control ( n = 152) group, respectively. The control group only received standard care, while the experimental group received standard care and passive music therapy during peripherally inserted central catheter placement (30–45 min) and after catheterization, until discharged from the hospital (twice a day, 30 min once). Measures include anxiety and vital signs (blood pressure, heart rate, and respiratory rate). Results: Repetitive measurement and analysis of variance showed that the patients in experimental group had a statistically significant decrease in anxiety, diastolic blood pressure, and heart rate over time compared to the control group, but no significant difference was identified in systolic blood pressure and respiratory rate. Conclusion: Passive music therapy can efficiently relieve the anxiety of lung cancer patients during peripherally inserted central catheter placement. It also can lower the patient’s diastolic blood pressure and slow down the heart rate. So, music therapy benefits patients with peripherally inserted central catheter.

Background This study aimed to investigate lung cancer patients and attitudes of their caregivers toward advance directives (ADs) in China. Methods A cross sectional study was conducted in the Department of Oncology outpatient clinic in West China Hospital, Sichuan University. A questionnaire was used to survey the attitudes of lung cancer patients and caregivers toward ADs. Results A total of 148 lung cancer patients and 149 caregivers were enrolled into the study. Of these, 94.6% and 89.9% of patients and caregivers had not heard of AD and none of those in the study had ever signed an AD. A total of 79.7% patients and 75.2% caregivers were willing to sign ADs after they were provided with information. Patients who preferred the end of life period to sign ADs were 5.4 times more likely to have ADs than patients who chose to sign ADs when their disease was diagnosed (P

Ovaries produce sex hormones, and ovariectomized animals are often used as models for ovarian dysfunction. The liver is a vital organ involved in metabolism and immunity. In the present study, we conducted experiments to investigate the effects of ovariectomy on transcription and metabolic processes in the liver in chicken. Eight Single Comb White Leghorn (SCWL) female chickens were ovariectomized at 17 wk of age, and 8 intact SCWL females served as controls. At 100 wk of age, all chickens were euthanized. High-throughput transcriptome sequencing was performed on liver RNA obtained from ovariectomized and intact females. A total of 267 differentially expressed genes (DEG) were identified in our study. After analysis using DAVID functional annotation tool, one significant Kyoto Encyclopedia of Genes and Genomes pathway, the phosphatidylinositol signaling pathway, was clustered. Gene Ontology enrichment analysis yielded 46 significant Gene Ontology terms. Among terms describing biological processes, the glycerolipid metabolic and lipid localization processes were dominant. The anabolic genes, PEPCK and GK5, and the catabolic genes, VTG1; VTG2; PLD5; DGKQ; DGKE; and FABP3, were detected in ovariectomized chickens. Differentially expressed genes such as ENSGALG00000000162, IL-1Β, SVOPL, and CA12 implied that livers in ovariectomized chickens were subjected to strong inflammatory reactions, whereas defenses against endogenous materials were compromised. A comprehensive view of gene expression in the liver of ovariectomized chickens would advance our understanding of lipid metabolism, glycometabolism, and their relationships to pathologies induced by absence of the ovary. The identified DEG indicated that ovariectomy disturbed lipid metabolism in the liver and was accompanied by an increase in hepatic gluconeogenesis and reductions in phosphatidic acid synthesis and lipid carrier capacity.

The cuticle formed in the uterus is the outermost layer as the first defense line of eggshell against microbial invasions in most avian species, and analyzing its genetic regulation and influencing factors are of great importance to egg biosecurity in poultry production worldwide. The current study compared the uterine transcriptome and proteome of laying hens producing eggs with good and poor cuticle quality (GC and PC, the top and tail of the cuticle quality distribution), and identified several genes involved with eggshell cuticle quality (ESCQ). Overall, transcriptomic analysis identified 53 differentially expressed genes (DEGs) between PC versus GC group hens, among which 25 were up-regulated and 28 were down-regulated. No differences were found in the uterine proteome. Several DEGs, including PTGDS, PLCG2, ADM and PRLR related to uterine functions and reproductive hormones, were validated by qPCR analysis. Egg quality measurements between GC and PC hens showed GC hens had longer laying interval between two consecutive ovipositions (25.64 ± 1.23 vs 24.94 ± 1.12 h) and thicker eggshell thickness (352.01 ± 23.04 vs 316.20 ± 30.58 μm) (P PTGDS, PLCG2, ADM and PRLR genes were discovered and might play crucial roles in cuticle deposition by regulating the uterine muscular activities and secretion function. The findings in the present study provide new insights into the genetic regulation of cuticle deposition in laying hens and establish a foundation for further investigations.

The gut microbiota of chickens plays an important role in host physiology. However, the colonization and prevalence of gut microbiota have not been well-characterized. Here, we performed 16S rRNA gene sequencing on the duodenal, cecal and fecal microbiota of broilers at 1, 7, 21, and 35 days of age and characterized the dynamic succession of microbiota across the intestinal tract. Our results showed that Firmicutes was the most abundant phylum detected in each gut site at various ages, while the microbial diversity and composition varied among the duodenum, cecum, and feces at different ages. The microbial diversity and complexity of the cecal microbiota increased with age, gradually achieving stability at 21 days of age. As a specific genus in the cecum, Clostridium_sensu_stricto_1 accounted for 83.50% of the total abundance at 1 day of age, but its relative abundance diminished with age. Regarding the feces, the highest alpha diversity was observed at 1 day of age, significantly separated from the alpha diversity of other ages. In addition, no significant differences were observed in the alpha diversity of duodenal samples among 7, 21, and 35 days of age. The predominant bacterium, Lactobacillus, was relatively low (0.68–6.04%) in the intestinal tract of 1-day-old chicks, whereas its abundance increased substantially at 7 days of age and was higher in the duodenum and feces. Escherichia-Shigella, another predominant bacterium in the chicken intestinal tract, was also found to be highly abundant in fecal samples, and the age-associated dynamic trend coincided with that of Lactobacillus. In addition, several genera, including Blautia, Ruminiclostridium_5, Ruminococcaceae_UCG-014, and [Ruminococcus]_torques_group, which are related to the production of short-chain fatty acids, were identified as biomarker bacteria of the cecum after 21 days of age. These findings shed direct light on the temporal and spatial dynamics of intestinal microbiota and provide new opportunities for the improvement of poultry health and production.

Poor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.

Xiying Chi,1 Tao Ji,1 Junying Li,2 Jie Xu,1 Xiaodong Tang,1 Lu Xie,1 Fanfei Meng,2 Wei Guo1 1Musculoskeletal Tumor Center, Peking University, People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Medicine, OrigiMed, Shanghai, 201114, People’s Republic of ChinaCorrespondence: Wei Guo; Tao JiMusculoskeletal Tumor Center, Peking University, People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail bonetumor@163.com; jitaomd@163.comObjective: The limited understanding of correlation between genomic features and biological behaviors has impeded the therapeutic breakthrough in osteosarcoma (OS). This study aimed to reveal the correlation of mutational and evolutionary traits with clinical outcomes.Methods: We applied a case-based targeted and whole exome sequencing of eleven matched primary, recurrent and metastatic samples from three OS patients characterized by different clinical behaviors in local recurrence or systematic progression pattern.Results: Extensive OS-associated driver genes were detected including TP53, RB1, NF1, PTEN, SPEN, CDKN2A. Oncogenic signaling pathways including cell cycle, TP53, MYC, Notch, WNT, RTK-RAS and PI3K were determined. MYC amplification was observed in the patient with shortest disease-free interval. Linear, branched or mixed evolutionary models were constructed in the three OS cases. A branched evolution with limited root mutation was detected in patient with shorter survival interval. ADAM17 mutation and HEY1 amplification were identified in OS happening dedifferentiation. Signatures 21 associated with microsatellite instability (MSI) was identified in OS patient with extra-pulmonary metastases.Conclusion: OS was characterized by complex genomic alterations. MYC aberration, limited root mutations, and a branched evolutionary model were observed in OS patient with relatively aggressive course. Extra-pulmonary metastases of OS might attribute to distinct mutational process pertaining to MSI. Further research in a larger number of people is needed to confirm these findings.Keywords: osteosarcoma, clinical behavior, root mutation, evolution, extra-pulmonary metastase, microsatellite instability

PurposeTo measure the sexual activity of breast cancer survivors and their partners to better understand the causes of sexual inactivity and sexual dissatisfaction in this population.MethodsWe investigated the proportion of sexual activity and sexual dissatisfaction in a cross‐sectional study and described their association with sexual health information sexual thoughts, socio‐demographic factors, body image, marital satisfaction, and mental health problems. We enrolled 438 eligible couples by convenient sampling. The statistical analysis and graphical work were completed using SPSS and Graphpad Prism.ResultsOf all participants, 58.66% (257/438) reported being sexually inactive. Of the 41.3% (181/438) sexually active participants, 96.7% (175/181) were considered to have sexual dysfunction. Patients’ sexual knowledge related to their disease, such as “sexual activity may impede disease recovery (AOR = 1.642; 95% CI: 1.119~2.409)”, “sexual activity may cause cancer recurrence or metastasis (AOR = 1.526; 95% CI: 1.012~2.302)”, “sexual activity could change the estrogen level and stimulate tumor growth (AOR = 1.585; 95% CI: 1.021~2.460)” were significantly associated with sexual inactivity. Psychological issues related to sexual activity, and hospital's sexual health resources, such as“anxiety (AOR = 2.141; 95% CI: 1.400~3.272)”, “depression (AOR =2.082; 95% CI: 1.317~3.293)”, “feeling less feminine as a result of your disease or treatment (AOR = 1.526; 95% CI: 1.012~2.302) ”, “dissatisfied with their physical appearance (AOR = 1.514; 95% CI: 1.010~2.271) ”, “medical providers provide information on sexual health (AOR = 4.459; 95% CI: 2.044~9.730) ”, “used sexual health aids (AOR = 1.514; 95% CI: 1.010~2.271) ” were significantly associated with sexual dissatisfaction. We also identified that the sexual demands of the partner led to increased sexual dissatisfaction among the survivors. ConclusionsMost Chinese breast cancer survivors were sexually inactive. Patients’ sexual knowledge related to their disease was the great barrier to sexual activity. Improving psychological problems associated with sexual activity and providing professional sexual health resources in hospitals can effectively improve sexual satisfaction among survivors. In addition, the impact of the partner's proactive needs on sexual satisfaction also needs to be considered when developing couples' therapy together.

OBJECTIVE To investigate the effect of open-flap or flapless approaches on the accuracy of implant placement partially guided by tooth-supported surgical templates. MATERIALS AND METHODS A total of 36 edentulous sites were selected from seven human cadaver heads. Following the preoperative implant planning using Blue Sky Plan, surgical guides were fabricated by an in-office desktop 3D printer. All the sites were randomly divided into two groups: flapless approach (n = 18), and open-flap approach (n = 18). After guided osteotomy preparation with subsequent freehand implant placement, digital intraoral scanning was performed to obtain post-operative implant positions. Based on the image registration, the deviations between the planned and actual implant position were measured and compared. RESULTS Statistically significant variance differences between the two approaches were found in the global coronal (open-flap: 0.86 ± 0.23 mm; flapless: 1.3 ± 0.62 mm; P

Statement of problem During a digital intraoral scan for an esthetic implant restoration, the peri-implant soft tissue will collapse rapidly after the interim restoration (IR) is removed, making it difficult to replicate the established emergence profile. The rate of this collapse is unclear. Purpose The purpose of this clinical study was to determine whether significant dimension differences could be found between peri-implant soft tissue supported by an IR and that immediately after removal of the restoration and to assess the changes over time. Material and methods Optical scans were made of 12 single implant sites in the esthetic zone of 10 participants. The scans in the first group replicated the peri-implant soft tissue contour with the support of the IR; in the second group, scans were made at different times from 0 seconds to 20 minutes after removal of the restoration. The changes in the soft tissue contour, including the height of the mesial papilla, distal papilla, and gingival margin, the facial and palatal soft tissue thickness, and emergence profile discrepancies (EPDs), were assessed. A linear mixed model was built to estimate the EPD. Results After the removal of IR, the palatal soft tissue thickness increased over time, and only minimal changes were found in the height of the mesial papilla, distal papilla, and gingival margin (up to −0.27 mm at 20 minutes). A significant EPD was immediately present at all the measurement sites after the removal of the IR. The linear mixed model showed a significant positive correlation between the natural logarithm of time and EPD. Significant positive correlations between gingiva thickness/implant depth and EPD were only seen at some of the sites. Conclusions A small reduction in the papilla level occurred, but no clinical influence on the proximal contact design of the restoration was detected. For the emergence profile, a significant but small discrepancy occurred immediately and continued to increase over time.

This study assessed the clinic outcomes of erbium: yttrium/aluminum/garnet (Er:YAG) laser and diode laser use in second phase of implant surgery. Fifty implants scheduled for stage II implant surgery were randomly assigned to 4 groups. In the first group (G1), Lite-touch Er:YAG laser was selected, and a vacuum-formed template was used for each site to indicate surgical entrance. For the second group (G2), Lite-touch Er:YAG laser was used and the surgery was performed in a free-hand way. The third group (G3) adopted free-hand surgery while diode laser was used. In the last group (G4), LightWalker Er:YAG laser was applied by free hand. The surgeon was allowed to look at cross-sectional images and 3D reconstruction in the computer to obtain implant position in G2, G3, and G4. The time of operation, healing time, and accuracy of operation were assessed. G1 and G4 took the shortest time in surgery than that of the other two groups (P 0.05). The healing time of Lite-touch Er:YAG laser with or without surgical guide was the shortest when compared with the other two groups (P

Background & aims The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. Methods In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. Results Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P = 0.024). Conclusions Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.

[Image: see text] Novel anthraquinone compounds that induce ER stress and paraptosis-like cell death were designed and synthesized. Compound 4a is the first organic micromolecule to kill tumor cells by only paraptosis, and its mechanism of action has been further explored. Paraptosis does not appear to involve either phosphatidylserine translocation associated with apoptosis or cell cycle arrest. The bisbenzyloxy and N-(2-hydroxyethyl)formamide structures may be two critical pharmacophores for paraptosis. Bisbenzyloxy can induce ER stress, and the N-(2-hydroxyethyl)formamide structure can increase the ratio of LC3II/I and cytoplasmic vacuolization and facilitates paraptosis. Some antitumor drugs fail to eradicate malignant cell lines with impaired apoptotic pathways; paraptosis may be a route to kill such cells and provides a new potential strategy for cancer chemotherapy.

The optimal conditioning regimen of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients with minimal residual disease (MRD) remains controversial. We studied the results in 98 high-risk acute leukemia patients transplanted with idarubicin (IDA)-intensified conditioning regimens between 2012 January and 2017 January. Among these patients, 31 (31.6%) had more than 5% marrow blasts at time of transplantation and 67 patients were in morphologic remission: MRD negative status at time of conditioning was achieved in 39 patients (39.8%), whereas 28 (28.6%) remained carriers of any other positive MRD level in the bone marrow. Three-year relapse estimates of patients with MRD-positive remission was 22.0%, which was remarkably lower than patients with active disease (45.4%, P = .027) but approximate to that of patients in MRD-negative remission (15.5%, P = .522). There were no significant differences in terms of 3-year estimated overall survival (OS) and disease-free survival (DFS) between MRD-positive remission and MRD-negative remission groups (71.4% versus 79.1% [P = .562] and 67.9% versus 76.9% [P = .634], respectively). Moreover, the estimated rates of 3-year OS and DFS of patients in MRD-positive remission were significantly better than those in patients with active disease (71.4% versus 41.9% [P = .033] and 67.9% versus 38.7% [P = .037], respectively). These data indicate that IDA-intensified conditioning allo-HSCT could overcome the negative prognostic impact of MRD.

Jingyu Wang,1 Shuke Ge,2 Yaqing Wang,1 Yi Liu,3 Lihua Qiu,4 Junying Li,4 Xin Huang,1 Li Sun1 1Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People’s Republic of China; 2Department of Emergency management, Liaoning Center for Disease Control and Prevention, Shenyang, 110000, Liaoning Province, People’s Republic of China; 3Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan Province, People’s Republic of China; 4Department of epigenetics, China Medical University, Shenyang, 110000, Liaoning Province, People’s Republic of ChinaCorrespondence: Li SunThe First Affiliated Hospital of China Medical University, North Nanjing Street 155#, Heping District of Shenyang, Liaoning Province, 110000, People’s Republic of ChinaTel +86 24-83282506Email sunlicmu1974@163.comPurpose: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms.Methods: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry.Results: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1β, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-β 1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated.Conclusion: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFβ 1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.Keywords: puerarin, UUO, CKD, inflammation, fibrosis

INTRODUCTIONS Intraoral scanner has been widely used for implant impression in partially edentulous cases; however, its accuracy in the impression of full-arch implant is still questionable. CLINICAL REPORT This clinical report presents a technique to check the accuracy of intraoral scanning for complete-arch implant restorations using an implant index cast (The Glossary of Prosthodontic Terms 9th Edition) and a three-dimensional printed cast. A clinical case of immediate loading on a maxillary edentulous patient illustrates the application of an implant index cast in implant fixed complete dentures (IFCDs). DISCUSSION The implant index cast was fabricated based on the immediate interim prosthesis and provides effective control of the fit of scanned files and printed models. Therefore, this approach allows a more predictable and accurate fit of the final prosthesis. CLINICAL SIGNIFICANCE In this article, we present a technique to check the accuracy of the final prosthesis without the need for a conventional impression and final cast in a digital workflow. This proposed approach is demonstrated through a case report of a maxillary edentulous patient restored with immediate loaded IFCDs.