Demineralized bone matrix for repair and regeneration of maxillofacial defects: A narrative review.

OBJECTIVES: Demineralized bone matrix (DBM) is a well-established bone graft material widely accepted by dentists and the public for its favorable osteoconductivity and osteoinductive potential. This article aimed to provide a narrative review of the current therapeutic applications and limitations of DBM in maxillofacial bone defects. STUDY SELECTION, DATA, AND SOURCES: Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic reviews. MEDLINE, PubMed, and Google Scholar were searched using keywords. CONCLUSIONS: Some evidence supported the therapeutic application of DBM in periodontal intrabony defects, maxillary sinus lifts, ridge preservation, ridge augmentation, alveolar cleft repair, orthognathic surgery, and other regional maxillofacial bone defects. However, the limitations of DBM should be considered when using it, including potential low immunogenicity, instability of osteoinductive potential, handling of the graft material, and patient acceptance. CLINICAL SIGNIFICANCE: With the increasing demand for the treatment of maxillofacial bone defects, DBM is likely to play a greater role as a promising bone graft material. Safe and effective combination treatment strategies and how to maintain a stable osteoinductive potential will be the future challenges of DBM research.

Exploring wound management in dental pulp: Utilizing single-cell RNA sequencing for global transcriptomic analysis in healthy and inflamed pulpal tissues.

The process of wound healing in the dental pulp is characterized by intricate interplay of signalling cascades, cellular responses, and extracellular matrix (ECM). The objective of this research was to examine the intricate interaction between signalling cascades, cellular responses, and extracellular matrix (ECM) dynamics that comprise the wound healing process of dental pulp. We conducted a controlled laboratory analysis of transcriptomic landscape of dental pulp tissues, including both healthy and inflamed samples, utilizing single-cell RNA sequencing. We identified significant change in cellular composition under carious conditions by analysing samples from 50 patients. Specifically, the proportion of immune cells increased from 25% to 40%, while the proportion of fibroblasts decreased from 20% to 10%. A transition towards ECM remodelling and fibrosis was indicated by this change. In addition, substantial increase inexpression of critical genes including COL1A1, FN1, IL-1B, IL-6 and TNC was detected, indicating that the extracellular matrix (ECM) was actively remodelled and that a robust inflammatory response was present, both of which are vital for tissue repair. Increased cell-cell interactions among B cells, plasma cells, macrophages and MSCs, and fibroblasts were highlighted in our study, demonstrating the intricate cellular dynamics that occur in response to dental pulp injury. The knowledge gained regarding the cellular and molecular processes underlying pulp wound healing contributed to the advancement of knowledge regarding pulp pathology and regeneration. Moreover, it established a foundation for creation of targeted therapeutic interventions that seek to maximize pulp repair and regeneration. This study represented noteworthy achievement in the field of dental surgery, establishing a solid groundwork for subsequent investigations into regenerative medicine, wound healing, and dental tissue restoration.

Isolation, characterization, and genomic analysis of a novel bacteriophage MA9V-1 infecting Chryseobacterium indologenes: a pathogen of Panax notoginseng root rot.

Chryseobacterium indologenes is one of the primary causative agents of root rot of Panax notoginseng, which significantly affected plant growth and caused economic losses. With the increasing incidence of antibiotic-resistant bacterial phytopathogens, phage therapy has been garnered renewed attention in treating pathogenic bacteria. However, the therapeutic potential of phage therapy on root rot of P. notoginseng has not been evaluated. In this study, we isolated a novel lytic phage MA9V-1 infecting C. indologenes MA9 from sewage and monitored the formation of clear and round plaques with a diameter of approximately 0.5-1.5 mm. Phage MA9V-1 exhibited rapid absorption (>75% in 8 min), a latency period of 20 min, and a burst size of 10 particles per cell. Transmission electron microscopy indicated that the phage MA9V-1 is a new myovirus hosting C. indologenes MA9. Sequencing of phage genomes revealed that phage MA9V-1 contained a linear double-stranded DNA genome of 213,507 bp with 263 predicted open reading frames, including phage structure, host lysing, and DNA polymerase/helicase but no genes of tRNA, virulence, and antibiotic resistance. Our proteomic tree and genomic analysis revealed that phage MA9V-1 shares identity with Sphingomonas phage PAU and Tenacibaculum phage PTm1; however, they also showed apparent differences. Further systemic evaluation using phage therapy experiments on P. notoginseng suggested that phage MA9V-1 can be a potential candidate for effectively controlling C. indologenes MA9 infection. Thus, we have presented a novel approach to solving root rot in P. notoginseng.

Chylous aqueous humor caused by hyperlipidemia: A case report and literature review.

RATIONALE: Generally, there is no lipoprotein in aqueous humor, and chyle usually exists transiently in the body. Therefore, persistent chylous aqueous humor is rare. PATIENT CONCERNS: We report a case of a 39-year-old man with persistent milky white appearance over the right eye. DIAGNOSES: The patient had a history of poorly controlled diabetes for the past 2 years and central retinal vein occlusion of the same eye for the past 2 weeks. The patient's right eye had a uniform milky appearance in the anterior chamber, transparent cornea, and no keratic precipitate in the posterior cornea. Color Doppler ultrasound of the affected eye showed no obvious inflammation in the vitreous cavity. Laboratory tests revealed severe chylemia. The patient was finally diagnosed as chylous aqueous humor. INTERVENTIONS AND OUTCOMES: After conventional hypolipidemia and hypoglycemia treatment and locally glucocorticoid treatment. The milky white changes in the anterior chamber improved considerably and finally disappeared. LESSONS: Although the impact of hyperlipidemia on the cardiovascular system and digestive system is well known, its impact on the eyes is often overlooked. We report a rare case of unilateral chylous aqueous humor caused by hyperlipidemia. Through the analysis of this special case, we recommend that ophthalmologists should pay attention to the impact of blood lipid change on eyes.

Traffic conflicts in the lane-switching sections at highway reconstruction zones.

INTRODUCTION: There are designated sections for lane-shifting in several highway reconstruction and expansion zones. Similar to the bottleneck sections of highways, these sections are characterized by poor pavement surface conditions, disorderly traffic flow, and high safety risk. This study examined the continuous track data of 1,297 vehicles collected using an area tracking radar. METHOD: The data from the lane shifting sections were analyzed in contrast with the regular section data. Further, the single-vehicle attributes, traffic flow factors, and the respective road characteristics in the lane-shifting sections were also taken into account. In addition, the Bayesian network model was established to analyze the uncertain interaction between the various other influencing factors. The K-Fold cross validation method was used to evaluate the model. RESULTS: The results showed that the model has a high reliability. The analysis of the model revealed that the significant influencing factors in decreasing order of their influence on the traffic conflict are: the curve radius, cumulative turning angle per unit length, standard deviation of the single-vehicle speed, vehicle type, average speed, and the standard deviation of the traffic flow speed. The probability of traffic conflicts is estimated to be 44.05% when large vehicles pass through the lane- shifting section while it is 30.85% for small vehicles. The probabilities of traffic conflict are 19.95%, 34.88%, and 54.79% when the turning angles per unit length are 0.20 °/m, 0.37 °/m, and 0.63 °/m, respectively. PRACTICAL APPLICATIONS: The results support the view that the highway authorities help reduce traffic risks on lane change sections by diverting large vehicles, implementing speed limits on road sections, and increasing the turning angle per unit length of vehicles.

GDF11 Improves Ischemia-Reperfusion-Induced Acute Kidney Injury via Regulating Macrophage M1/M2 Polarization.

INTRODUCTION: Acute kidney injury (AKI) is a clinical emergency caused by the rapid decline of renal function caused by various etiologies. Growth differentiation factor 11 (GDF11) can promote renal tubular regeneration and improve kidney function in AKI, but the specific mechanism remains unclear. Herein, we investigated the effect and mechanisms of GDF11 in ameliorating AKI induced by ischemia-reperfusion (I/R). METHODS: An animal model of AKI was established by I/R method, and the changes of serum urea nitrogen and creatinine were measured to evaluate the AKI. Enzyme-linked immunosorbent assay (ELISA) was used to measure cytokines, malondialdehyde, superoxide dismutase, nitric oxide synthase, and arginase 1 levels. Flow cytometry was used to count the M1/M2 macrophages. IHC, WB, and q-PCR experiments were used to evaluate the expression of GDF11. RESULTS: The changes in serum levels of urea nitrogen and creatinine after I/R suggest that an animal model of AKI induced by I/R was successfully established. AKI caused by I/R significantly changed the M1/M2 macrophage polarization balance, with an increase in M2 being significantly higher than M1 as well as increased oxidative stress. Treatment with GDF11 after I/R significantly increased the differentiation of M2 cells and inhibited the differentiation of M1 macrophages, as well as decreased oxidative stress. CONCLUSION: GDF11 can promote the repair of AKI caused by I/R by regulating the balance of M1/M2 polarization in macrophages and oxidative stress.

Extremely dangerous hypopituitarism related long QT syndrome and transient ST-segment elevation: A case report.

Acquired long QT syndrome caused by hypopituitarism and transient ST-segment elevation has not been reported in cardiac arrest patients. We report a case of extremely dangerous acquired long QT syndrome and transient ST-segment elevation. A 44-year-old Chinese woman with renal failure experienced sudden cardiac arrest in the haemodialysis room. Subsequent electrocardiogram showed QT prolongation and transient ST-segment elevation. This patient's medical history, subsequent laboratory results and pituitary magnetic resonance imaging suggested hypopituitarism. Transient ST-segment elevation on the electrocardiogram was considered to be caused by repeated direct current shocks. The patient was diagnosed with acquired long QT syndrome and was not taking any antiarrhythmic drugs. Her corrected QT interval normalized after hormone replacement therapy. This case highlights the importance of the awareness of hypopituitarism; early identification and intervention can prevent the occurrence of this life-threatening arrhythmia. ST-segment elevation is not always due to acute myocardial infarction, and a variety of other causes, especially electrical cardioversion, should be considered.

Complete recovery of the retinal pigment epithelium layer after spontaneous large serous retinal pigment epithelial tear.

INTRODUCTION: The objective of this study is to report a case of complete recovery of the retinal pigment epithelium (RPE) layer after spontaneous large serous RPE tear and explore the possible RPE repair mechanism. CASE DESCRIPTION: A 63-year-old male patient developed serous detachment of the RPE in the macula of his left eye. During the follow-up period, an oval-shaped RPE tear spontaneously occurred in the macular area, and fundus autofluorescence showed that the torn area was 6.59 mm2. Spectral-domain optical coherence tomography (OCT) revealed that the subretinal fluid had been absorbed and that the continuity of the RPE layer was gradually restored from the periphery to the center over the course of 9 months. Moreover, visual acuity (VA) in the left eye was restored to 20/20, and there was no significant difference in macular function between the two eyes, as measured by multifocal electroretinography, at the last follow-up. In addition, the patient received no special treatment during the entire follow-up period. CONCLUSION: The integrity of the RPE layer can be restored completely after extensive RPE tear, and recovered RPE may allow the recovery of macular function.

CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line.

Cataract is a global eye disease caused by the opacification of lens, while its underlying molecular pathogenesis is not clear, making it difficult for prevention. CELF1, an RNA binding protein, mediates Alternative Splicing (AS) of genes involved in diverse diseases and regulates development or defects of lens. Utilizing transcriptome-wide approaches, we analyzed and compared AS patterns between human lens epithelial cells (SRA01/04) with CELF1 overexpression (CELF1-OE) and control cells. Extensive changes in AS patterns upon CELF1-OE were identified in SRA01/04 cells. We finally identified 840 CELF1-regulated AS events (RASEs) and found that CELF1-OE preferred to repress exon skipping events in SRA01/04 cells. CELF1-regulated AS genes were enriched in the regulation of DNA repair, cellular response to DNA damage stimulus, and apoptosis pathways (including HMGA2, CSNK1E, and YAP1). These biological functions and pathways have been reported to be associated with lens development or other eye diseases. To further explore the mechanisms of CELF1 in regulating AS genes, we downloaded and re-analyzed a set of CELF1-RNA interactome data. We found that 194 genes were bound and regulated by CELF1 at the AS level. 10 genes involved in DNA repair-related pathways were also bound by CELF1. Motif analysis for CELF1-bound peaks and splicing sites of RASEs showed that CELF1 regulates AS by binding to the AGGU[AG]AG motif in SRA01/04 cells. CELF1 could mediate AS of DNA repair-related genes through directly binding to their transcripts with distinct motif bias. The functional mechanism of CELF1 may ultimately participate in cataract formation and lens development.

A missed case of hereditary hemorrhagic telangiectasia: A case report.

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disorder characterized by abnormal blood vessel formation. When an abnormal vascular architecture affects the lungs and central nervous system, serious complications can occur. We report a missed case of hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations and cerebral arteriovenous malformations. A 22-year-old Chinese female was taken to the emergency room because of unconsciousness. Emergency head contrast-enhanced computed tomography and transthoracic contrast echocardiography showed that she had cerebral arteriovenous malformations and pulmonary arteriovenous malformations. The patient experienced multiple spontaneous epistaxis since childhood, for which she was treated at a local hospital for a brief period. Her mother also had pulmonary arteriovenous malformations. The patient was diagnosed with hereditary hemorrhagic telangiectasia according to the consensus Curaçao diagnostic criteria and eventually died of hereditary hemorrhagic telangiectasia. The case report highlights the importance of early diagnosis and intervention for hereditary hemorrhagic telangiectasia. Given that hereditary hemorrhagic telangiectasia is frequently undiagnosed, increasing the physician's awareness of hereditary hemorrhagic telangiectasia can play an important role in the timely diagnosis and treatment of these patients.

The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy.

BACKGROUND: This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis. METHODS: Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients. RESULTS: Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy. CONCLUSIONS: RPE and choroidal atrophy were found to play an important role in the development of macular caldera.

Two-minute walk distance reference equations for middle-aged and elderly Chinese individuals with obesity.

BACKGROUND AND OBJECTIVE: While the six-minute walk test (6MWT) is often used to assess exercise capacity, the less well-known two-minute walk test (2MWT) is more feasible for some patients. In previous studies, we developed reference equations for the two-minute walk distance (2MWD) for healthy Chinese adults. However, our study did not recruit people with obesity, and the reference equations did not apply to participants with a body mass index (BMI) > 30 kg/m2. The main objective of this study was to establish reference equations for the 2MWD among middle-aged and elderly Chinese individuals with obesity. METHODS: A total of 295 individuals were recruited. The participants underwent two 2MWTs, with the longer of the two 2MWDs used for further analyses. The reference equations for the 2MWD were developed using stepwise multiple regression analysis. The newly established equations for the 2MWD were then compared with the existing equations. RESULTS: The mean 2MWD of the participants was 176±20 m. Age and BMI were identified as independent factors that influenced the 2MWD and explained 28% and 32% of the variance in walking distance for the male and female groups, respectively. The reference equations for the 2MWD were as follows: [Formula: see text]. CONCLUSION: This study resulted in the development of reference equations for predicting 2MWD among middle-aged and elderly Chinese people with obesity. These equations will be a clinically valuable tool for evaluating functional capacity, determining prognoses and monitoring treatment in middle-aged and elderly Chinese people with obesity.

Reference equations for the six-minute walking distance in obese Chinese subjects more than 40 years old.

BACKGROUND: Studies have shown that the reference equations for the six-minute walking distance (6MWD), which were mainly derived from healthy, normal-weight people, are not suitable for individuals with obesity. The main purpose of this study was to establish reference equations for the 6MWD in obese Chinese subjects. METHODS: In our study, a total of 214 individuals with obesity performed the six-minute walking tests (6MWTs) according to the American thoracic society (ATS) guidelines, and the longer 6MWD was used for further analysis. The reference equations for the 6MWD were developed using stepwise multiple regression analysis. The newly established equations for the 6MWD were compared to the existing prediction equations. RESULTS: The mean 6MWD for the cohort was 523 ± 56 m. We found that the reliability of two 6MWTs was good. Age and BMI were identified as independent factors, and explained 31% and 27% of the variance in the 6MWD for the male and female participants, respectively. Thus, the reference equations reported in the previous studies did not accurately predict the 6MWD in our subjects. CONCLUSION: Our study was the first to describe the 6MWD in obese Chinese subjects and to propose new predictive equations. These established equations can improve the assessment of the health of obese Chinese patients whose exercise capacity is affected by the disease. LEVEL OF EVIDENCE: III, Cohort study.

CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells.

BACKGROUND: RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. METHODS: In this study, we overexpressed CELF1 in human cultured lens epithelial SRA01/04 cells and applied whole transcriptome sequencing (RNA-seq) method to analyze the global differences mediated by CELF1. We then analyzed public RNA-seq and CELF1-RNA interactome data to decipher the underlying mechanisms. RESULTS: The results showed that transcriptome profile was globally changed by CELF1 overexpression (CELF1-OE). Functional analysis revealed CELF1 specifically increased the expression of genes in extracellular matrix disassembly, extracellular matrix organization, and proteolysis, which could be classified into matrix metalloproteinases (MMPs) family. This finding was also validated by RT-qPCR and public mouse early embryonic lens data. Integrating analysis with public CELF1-RNA interactome data revealed that no obvious CELF1-binding peak was found on the transcripts of these genes, indicating an indirectly regulatory role of CELF1 in lens epithelial cells. CONCLUSIONS: Our study demonstrated that CELF1-OE promotes transcriptional level of MMP genes; and this regulation may be completed by other ways except for binding to RNA targets. These results suggest that CELF1-OE is implicated in the development of lens, which is associated with cataract and expands our understanding of CELF1 regulatory roles as an RNA binding protein.

Common clinical features of unilateral retinal pigment epithelium dysgenesis and combined hamartoma of the retina and retinal pigment epithelium.

BACKGROUND: Herein, we report two cases of unilateral retinal pigment epithelium dysgenesis (URPED) in Chinese patients and explore the relationship between URPED and combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). CASE PRESENTATION: The lesion margins in the two cases showed pathognomonic clinical features of URPED, namely, a scalloped reticular margin in hyperplastic retinal pigment epithelium and mild fibrosis. The hypoautofluorescence observed by fundus autofluorescence was inverted compared with that observed by fundus fluorescence angiography. A large amount of fibroglial proliferation and disorganization of the retina involving the whole layer, which are also found in peripapillary CHRRPE, were found in the lesions. CONCLUSIONS: URPED appears to share some clinical features with CHRRPE, and the relationship between URPED and CHRRPE needs further study.

Prediction model for cardiovascular disease risk in hemodialysis patients.

PURPOSE: To derive and validate a prediction score for cardiovascular disease (CVD) risk in hemodialysis patients in China. METHODS: Three hundred and eighty-eight patients with regular hemodialysis for more than 3 months were recruited from January 1, 2015 to September 30, 2019 and followed up till May 31, 2020. We derived a prediction score using all participants as a training data set and validated using a bootstrap validation data set. Discriminatory ability of the prediction score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Of 388 patients without CVD at baseline, 132 developed first CVD events during an average follow-up of 3.27 (inter-quartile range = 3.08) years. Of 26 clinical parameters, age, hypertension, diabetes and abnormal white blood cell (WBC) count were identified as significant predictors and included in the prediction model. Compared to those without any of these risk factors, those with one, two, and three to four points showed increased risks of CVD, with the adjusted hazards ratio and 95% confidence interval (CI) being 3.29 (1.17-9.26), 7.42 (2.68-20.51) and 15.43 (5.44-43.75), respectively. The score showed satisfactory discriminatory ability in both training and validation data set (AUC = 0.7025, 95% CI 0.6520-0.7530, and 0.6876, 95% CI 0.6553-0.7200, respectively). CONCLUSION: We derived and validated a prediction score for CVD risk in hemodialysis patients in China. Given there is a rapid increase in the number of hemodialysis patients, this simple point score can be used to identify high-risk individuals in clinical practice for more precise and efficient personalized treatment.

Deep Learning Technology in Pathological Image Analysis of Breast Tissue.

To explore the application value of the multilevel pyramid convolutional neural network (MPCNN) model based on convolutional neural network (CNN) in breast histopathology image analysis, in this study, based on CNN algorithm and softmax classifier (SMC), a sparse autoencoder (SAE) is introduced to optimize it. The sliding window method is used to identify cells, and the CNN + SMC pathological image cell detection method is established. Furthermore, the local region active contour (LRAC) is introduced to optimize it and the LRAC fine segmentation model driven by local Gaussian distribution is established. On this basis, the sparse automatic encoder is further introduced to optimize it and the MPCNN model is established. The proposed algorithm is evaluated on the pathological image data set. The results showed that the Acc value, F value, and Re value of pathological cell detection of CNN + SMC algorithm were significantly higher than those of the other two algorithms (P < 0.05). The Dice, OL, Sen, and Spe values of pathological image regional segmentation of CNN algorithm were significantly higher than those of the other two algorithms, and the difference was statistically significant (P < 0.05). The accuracy, recall, and F-measure of the optimized CNN algorithm for detecting breast histopathological images were 85.25%, 89.27%, and 80.09%, respectively. In the two databases with segmentation standards, the segmentation accuracy of MPCNN is 55%, 73.1%, 78.8%, and 82.1%. In the deep convolution network model, the training time of the MPCNN algorithm is about 80 min. It shows that when the feature dimension is low, the feature map extracted by MPCNN is more effective than the traditional feature extraction method.

Correction: Shao et al. AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells. Int. J. Mol. Sci. 2017, 18, 350.

The authors wish to make the following corrections to this paper [...].

The response of anti-VEGF therapy and tamoxifen withdrawal of tamoxifen-induced cystoid macular edema in the same patient.

BACKGROUND: Numerous cases with ocular toxicity secondary to tamoxifen have been reported, and became more apparent with keratopathy, cataract, optic neuritis, macular holes, crystalline retinopathy with or without cystoid macular edema (CME). Withdrawing tamoxifen with the approval of the oncologist is the major treatment for cases with tamoxifen-induced retinopathy. CASE PRESENTATION: We herein reported a patient with a two-year history of painless and reduced visual acuity in both eyes who received tamoxifen therapy for 6 years. Tamoxifen-induced rentinopathy with CME showed significant development even though the patient has already discontinued tamoxifen treatment for 6 months. Anatomic improvements after intravitreal ranibizumab injection in both eyes were significant but were temporary. Surprisingly, CME in both eyes has been resolved spontaneously after 10 months in the penultimate visit without any therapy. CONCLUSION: Intravitreal ranibizumab injection temporarily improved the anatomy of the eyes in a case with tamoxifen-induced CME, and only tamoxifen withdrawal can bring a sustained effect.