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Dental biofilm is the initiating factor of oral diseases, such as periodontitis and caries. Orthodontic treatment could alter the microbiome structure balance, and increase the risk of such diseases. Furthermore, fixed appliances can induce temporary changes in the microbiome community, and the changes that clear aligners bring are smaller by comparison. Temporary anchorage devices (TADs) are skeletal anchorages that are widely used in orthodontic treatment. Microorganisms affect the occurrence and development of inflammation surrounding TADs. At present, existing researches have verified the existence of plaque biofilm on the surface of TADs, but the formation of plaque biofilm and plaque composition under different stable conditions have not been fully understood. The development of high-throughput sequencing, molecular biology experiments, and metabonomics have provided new research ideas to solve this problem. They can become an effective means to explore the microbiome surrounding TADs.

Cervical adenocarcinoma (CAC) comprises a heterogeneous group of tumors that are not universally associated with HPV infection. As has been shown in other organs, it is becoming increasingly apparent that HPV status significantly affects the prognosis of adenocarcinoma. We conducted a systematic review and meta-analysis to investigate the infection status of high-risk Human papillomavirus (hrHPV) in CAC and evaluate its impact on the survival of patients.PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to May 1st, 2022. Data on HPV infection status and survival outcomes were evaluated using STATA 16.0.Seventy-one studies with 11,278 participants were included in HPV infection analysis and eight studies with 1099 participants were included in prognosis analysis. The HPV infection rate (including high-risk and low-risk) and hrHPV infection rate in CAC were 75% (95% CI 0.70-0.80, 6978 participants) and 75% (95% CI 0.70-0.81, 4906 participants), respectively. HPV-16 and -18 were the most common HPVs in CAC, with pooled infection rates of 37% (95% CI 0.33-0.41, 7848 participants) and 34% (95% CI 0.30-0.38, 7730 participants), respectively. hrHPV infection was associated with better overall survival (HR 0.23, 95% CI 0.11-0.47, 1013 participants), better disease-free survival (HR 0.18, 95% CI 0.07-0.43, 292 participants), better progression-free survival (HR 0.20, 95% CI 0.08-0.47, 271 participants) and less recurrence (RR 0.30, 95% CI 0.07-0.43, 181 participants).HPV infection rates were high in CAC. HPV-16 and -18 had the highest infection rates in CAC. However, hrHPV infection was associated with better survival and less recurrence. Future studies should clarify the relationship between hrHPV infection and other prognostic factors and make reasonable treatment strategies for CAC with different HPV status.CRD42022319390.

Traditional Chinese medicine (TCM) has significantly contributed to protecting human health and promoting the progress of world civilization. A total of 2,711 TCMs are included in the 2020 version of the Chinese Pharmacopoeia, which is an integral part of the world’s medical resources. Tu Youyou and her team discovered and purified artemisinin. And their contributions made the values and advantageous effects of TCM more and more recognized by the international community. There has been a lot of studies on TCM to treat diseases through antioxidant mechanisms, the reports on the new mechanisms beyond antioxidants of TCM has also increased year by year. Recently, many TCMs appear to have significant effects in regulating ferroptosis. Ferroptosis is an iron-dependent, non-apoptotic, regulated cell death characterized by intracellular lipid peroxide accumulation and oxidative membrane damage. Recently, accumulating studies have demonstrated that numerous organ injuries and pathophysiological process of many diseases are companied with ferroptosis, such as cancer, neurodegenerative disease, acute renal injury, arteriosclerosis, diabetes, and ischemia-reperfusion injury. This work mainly introduces dozens of TCMs that can regulate ferroptosis and their possible mechanisms and targets.

Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.

To explore the mortality of patients with fragile hip fractures and assess the death-associated risk factors.A total of 690 patients with osteoporotic hip fractures (age, 50-103 years) that were treated from January 2010 to December 2015 were enrolled and followed-up in this study and the clinical data were retrospectively collected. Three months, 1 year, and the total mortality were measured. Mortality-related risk factors were assessed including age, gender, surgery, the duration from injury to operation, pulmonary infection, and the number and type of complications. The mortality of each group was compared by chi-square test or corrected chi-square test for univariate analysis, and the factors with statistically significant mortality difference confirmed by univariate analysis were analyzed by binary logistic multivariate analysis.The 3-month mortality was 7.69%, the 1-year mortality was 15.60%, and the total mortality of the follow-up time was 24.06%. The 1-year and total mortality during the follow-up of the patients were higher in the75-year-old group than those in the ≤75-year-old group (p = 0.000, respectively); were higher in the male patients than that in the female patients (p = 0.042; p = 0.017, respectively); were significantly lower in the operation group than that in the non-operation group (p = 0.000, respectively); were significantly lower in the patients that underwent the operation in ≤5 days than the patients that underwent the operation within5 days (p = 0.008; p = 0.000, respectively); were significantly lower in patients with2 kinds of combined medical diseases than those with ≥2 kinds of chronic diseases (p = 0.000, respectively); were significantly lower in patients receiving anti-osteoporosis treatment than in patients not receiving anti-osteoporosis treatment (p = 0.000, p = 0.002, respectively). Binary logistic regression analysis showed that the independent risk factors affecting mortality included advanced age 75-years-old (OR = 5.653, p = 0.000), male (OR = 1.998, p = 0.001), non-surgical treatment (OR = 9.909, p = 0.000), the number of combined medical diseases ≥2 (OR = 1.522, p = 0.042), and non-anti-osteoporosis treatment (OR = 1.796, p = 0.002).Age, whether or not surgical treatment was performed, the number of medical diseases, and whether or not anti-osteoporosis treatment was performed were independent risk factors for 3-month and 1-year mortality in patients with fragile hip fractures.

We aimed to investigate the association between polysocial risk score (PsRS), an estimator of individual-level exposure to cumulative social risks, and incident type 2 diabetes in the UK Biobank study.This study includes 319,832 participants who were free of diabetes, cardiovascular disease and cancer at baseline in the UK Biobank study. The PsRS was calculated by counting the 12 social determinants of health from three social risk domains (namely socioeconomic status, psychosocial factors, and neighbourhood and living environment) that had a statistically significant association with incident type 2 diabetes after Bonferroni correction. A healthy lifestyle score was calculated using information on smoking status, alcohol intake, physical activity, diet quality and sleep quality. A genetic risk score was calculated using 403 SNPs that showed significant genome-wide associations with type 2 diabetes in people of European descent. The Cox proportional hazards model was used to analyse the association between the PsRS and incident type 2 diabetes.During a median follow-up period of 8.7 years, 4427 participants were diagnosed with type 2 diabetes. After adjustment for major confounders, an intermediate PsRS (4-6) and high PsRS (≥7) was associated with higher risks of developing type 2 diabetes with the HRs being 1.38 (95% CI 1.26, 1.52) and 2.02 (95% CI 1.83, 2.22), respectively, compared with those with a low PsRS (≤3). In addition, an intermediate to high PsRS accounted for approximately 34% (95% CI 29, 39) of new-onset type 2 diabetes cases. A healthy lifestyle slightly, but significantly, mitigated PsRS-related risks of type 2 diabetes (pA higher PsRS was related to increased risks of type 2 diabetes. Adherence to a healthy lifestyle may attenuate elevated diabetes risks due to social vulnerability. Genetic susceptibility and disadvantaged social status may act synergistically, resulting in additional risks for type 2 diabetes.

The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex-specific associations between total and regional FMR and incident dementia.A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis.During a median 8.65 years of follow-up, we documented 2 225 incident all-cause dementia cases, including 836 AD and 468 VD cases. There was an L-shaped association between whole body FMR and all-cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non-linear0.001 in men and women), where all-cause dementia risk decreased steeply with increasing FMR and levelled off at around the medians (0.35 in men, 0.61 in women) with a hazard ratio (HR) of 0.78 (95% CI: 0.64, 0.96; P = 0.019) and 0.60 (0.47, 0.77;0.001) per 1 standard deviation (SD) increase in men and women, respectively. Compared with other body parts, FMR of the leg showed the strongest inverse associations [HR (95% CI; P) per 1 SD below the medians: 0.60 (0.48, 0.75;0.001); 0.61 (0.47, 0.79;0.001) in men and women, respectively]. Specifically, the inverse associations of whole body FMR on all-cause dementia risk were significant only among participants over the age of 60 (P for trend0.001). Multivariable adjusted Cox models showed inverse associations of whole body FMR with AD in men only (P for trend = 0.003), whereas no statistically significant decrease was detected in VD among men and women.Our analyses provide strong evidence for L-shaped associations of total and regional FMR with the development of dementia among participants aged 60 years or older independent of overall obesity.

Adrenal incidentalomas are common lesions found on abdominal imaging, most of which are lipid-rich adrenal adenomas. Imaging diagnoses differentiating lipid-poor adrenal adenomas (LPA) from non-adenomas (NA) are presently challenging to perform. The aim of the study was to investigate the diagnostic performance of the relative enhancement ratio parameter in identifying LPA from NA.We retrospectively evaluated consecutively presenting patients with lipid-poor adrenal lesions (January 2015 to August 2021). Lesions were divided into LPA and NA (including hyperenhancing and hypoenhancing NA). Kruskal-Wallis and Bonferroni tests were used to determine the differences in feature parameters between these three groups. Receiver operating characteristic curve analysis was performed to determine the sensitivity for diagnosing LPA and NA at 95% specificity; the parameters were compared using the McNemar test.A total of 253 patients (mean age, 55 ± 12 years; 135 men), 121 with LPA and 132 with NA, were analyzed herein. The sensitivity (achieved at 95% specificity) of the relative enhancement ratio was higher than that of unenhanced attenuation in differentiating LPA from NA (60% vs. 52%, p = 0.064). The relative enhancement ratio yielded a higher sensitivity than unenhanced attenuation (79% vs. 59%, p 0.001) in differentiating LPA from hypoenhancing NA, and a lower sensitivity (26% vs. 69%, p 0.001) in differentiating LPA from hyperenhancing NA.The relative enhancement ratio showed better diagnostic performance than unenhanced attenuation in differentiating LPA from hypoenhancing NA, while simultaneously showing poor diagnostic performance in identifying LPA from all NA.

A major challenge to the clinical translation of tissue-engineered ear scaffolds for ear reconstruction is the limited auricular chondrocyte (hAuC) yield available from patients. Starting with a relatively small number of chondrocytes in culture results in dedifferentiation and loss of phenotype with subsequent expansion. To significantly decrease the number of chondrocytes required for human elastic cartilage engineering, we co-cultured human mesenchymal stem cells (hMSCs) with HAuCs to promote healthy elastic cartilage formation. HAuCs along with human bone marrow-derived hMSCs were encapsulated into 1% Type I collagen at 25 million/mL total cell density with different ratios (HAuCs/hMSCs: 10/90, 25/75, 50/50) and then injected into customized 3D-printed polylactic acid (PLA) ridged external scaffolds, which simulate the shape of the auricular helical rim, and implanted subcutaneously in nude rats for 1, 3 and 6 months. The explanted constructs demonstrated near complete volume preservation and topography maintenance of the ridged "helical" feature after 6 months with all ratios. Cartilaginous appearing tissue formed within scaffolds by 3 months, verified by histologic analysis demonstrating mature elastic cartilage within the constructs with chondrocytes seen in lacunae within a Type II collagen and proteoglycan-enriched matrix, and surrounded by a neoperichondrial external layer. Compressive mechanical properties comparable to human elastic cartilage were achieved after 6 months. Co-implantation of hAuCs and hMSCs in collagen within an external scaffold efficiently produced shaped human elastic cartilage without volume loss even when hAuC comprised only 10% of the implanted cell population, marking a crucial step toward the clinical translation of auricular tissue engineering.

Recent studies showed the potential of MRI-based deep learning (DL) for assessing treatment response in rectal cancer, but the role of MRI-based DL in evaluating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation remains unclear.To develop a DL method based on T2-weighted imaging (T2WI) and clinical factors for noninvasively evaluating KRAS mutation in rectal cancer.Retrospective.A total of 376 patients (108 women [28.7%]) with histopathology-confirmed rectal adenocarcinoma and KRAS mutation status.A 3 T, turbo spin echo T2WI and single-shot echo-planar diffusion-weighted imaging (b = 0, 1000 sec/mmA clinical model was constructed with clinical factors (age, gender, carcinoembryonic antigen level, and carbohydrate antigen 199 level) and MRI features (tumor length, tumor location, tumor stage, lymph node stage, and extramural vascular invasion), and two DL models based on modified MobileNetV2 architecture were evaluated for diagnosing KRAS mutation based on T2WI alone (image model) or both T2WI and clinical factors (combined model). The clinical usefulness of these models was evaluated through calibration analysis and decision curve analysis (DCA).Mann-Whitney U test, Chi-squared test, Fisher's exact test, logistic regression analysis, receiver operating characteristic curve (ROC), Delong's test, Hosmer-Lemeshow test, interclass correlation coefficients, and Fleiss kappa coefficients (P 0.05 was considered statistically significant).All the nine clinical-MRI characteristics were included for clinical model development. The clinical model, image model, and combined model in the testing cohort demonstrated good calibration and achieved areas under the curve (AUCs) of 0.668, 0.765, and 0.841, respectively. The combined model showed improved performance compared to the clinical model and image model in two cohorts. DCA confirmed the higher net benefit of the combined model than the other two models when the threshold probability is between 0.05 and 0.85.The proposed combined DL model incorporating T2WI and clinical factors may show good diagnostic performance. Thus, it could potentially serve as a supplementary approach for noninvasively evaluating KRAS mutation in rectal cancer.3 TECHNICAL EFFICACY: Stage 2.

Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and loss of projection of the reconstructed nipple. The use of unprocessed costal cartilage (CC) as an internal support for the reconstructed nipple has not been widely adopted because of the excessively firm resultant construct. Herein we use a 3D-printed Poly-4-Hydroxybutyrate (P4HB) bioabsorbable scaffold filled with mechanically processed patient-derived CC to foster ingrowth of tissue in vivo to protect the regenerated tissue from contractile forces as it matures. After 6 months in vivo, newly formed spongy fibrovascular cartilaginous tissue was noted in processed CC filled 3D-printed scaffolds, which maintained significantly greater projection than reconstructions without scaffolds. Interestingly, 3D-printed P4HB scaffolds designed with an internal 3D lattice of P4HB filaments (without CC) displayed the fastest material absorption and vascularized adipose-fibrous tissue as demonstrated by SEM and histological analysis, respectively. Using 3D-printed P4HB scaffolds filled with either processed CC, a 3D P4HB lattice or no fills, we have engineered neo-nipples that maintain projection over time, while approximating the biomechanical properties of the native human nipple. We believe that this innovative 3D-printed P4HB nipple reconstruction scaffold will be readily translatable to the clinic. STATEMENT OF SIGNIFICANCE: Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and substantial loss of projection of the reconstructed nipple, leading to significant patient dissatisfaction. Using 3D-printed P4HB scaffolds filled with either processed costal cartilage or 3D P4HB lattices, we have engineered neo-nipples that resist the forces induced by scar contracture, resulting in maintenance of neo-nipple projection over time and biomechanically approximating human nipples after 6 months in vivo implantation. This novel 3D-printed bioabsorbable P4HB scaffold will be readily translatable to the clinic to reconstruct nipples with patient-specific dimensions and long-lasting projection.

Background: Increasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging to explore human sinoatrial node (SAN) pathophysiology due to difficulty in isolating and culturing human SAN cells. Embryonic stem cells (ESCs) can be a source to derive human SAN-like pacemaker cells for disease modeling. Methods: We used both a hamster model and human ESC (hESC)–derived SAN-like pacemaker cells to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pacemaker cells of the heart. In the hamster model, quantitative real-time polymerase chain reaction and immunostaining were used to detect viral RNA and protein, respectively. We then created a dual knock-in SHOX2:GFP;MYH6:mCherry hESC reporter line to establish a highly efficient strategy to derive functional human SAN-like pacemaker cells, which was further characterized by single-cell RNA sequencing. Following exposure to SARS-CoV-2, quantitative real-time polymerase chain reaction, immunostaining, and RNA sequencing were used to confirm infection and determine the host response of hESC-SAN–like pacemaker cells. Finally, a high content chemical screen was performed to identify drugs that can inhibit SARS-CoV-2 infection, and block SARS-CoV-2–induced ferroptosis. Results: Viral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs functional human SAN-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis. Conclusions: Using a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.

We estimated the optimum time to initiate antiretroviral therapy (ART) in a retrospective observational cohort. We observed that ART initiation 7 days or less ( n = 817) and 8-30 days ( n = 1009) were the most important factors with viral suppression, and had similar viral suppression rate, CD4 + T-cell count increase and fractions of individuals with links at least 4 and individuals linked to recent HIV infection in HIV molecular networks. This study provides real-world evidence on the benefits of rapid ART initiation in resource-limited setting.

Background Abnormal alternative splicing is frequently associated with carcinogenesis. In B-cell acute lymphoblastic leukemia (B-ALL), double homeobox 4 fused with immunoglobulin heavy chain (DUX4/IGH) can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript (ERGalt ) and other splicing variants. However, the molecular mechanism underpinning this process remains elusive. Here, we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia. Methods The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients. X-ray crystallography, small angle X-ray scattering (SAXS), and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element (DRE)-DRE sites. The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity. To check whether recombination-activating gene 1/2 (RAG1/2) was required for DUX4/IGH-driven splicing, the proximity ligation assay, co-immunoprecipitation, mammalian two hybrid characterizations, in vitro RAG1/2 cleavage, and shRNA knock-down assays were performed. Results We reported previously unrecognized intron retention events in C-type lectin domain family 12, member A abnormal transcript (CLEC12Aalt ) and chromosome 6 open reading frame 89 abnormal transcript (C6orf89alt ), where also harbored repetitive DRE-DRE sites. Supportively, X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain (HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites. Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt , CLEC12Aalt , and C6orf89alt biogenesis, resulting in marked alleviation of its inhibitory effect on B-cell differentiation. Furthermore, we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes. Supportively, shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt , CLEC12Aalt , and C6orf89alt . Conclusions All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites, catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.

Being one of the most important exocrine fluids of the human body, saliva can reflect the health status of the body. Soliva collection has various advantages--it is simple, painless, fast, and safe, and soliva can be collected multiple times a day. Therefore, it has been gradually applied in the exploration for biomarkers for disease detection, providing a basis for the monitoring of the course of diseases, medication monitoring, and efficacy evaluation. We should implement health management based on saliva testing, collect the medical data of the healthy and diseased individuals and monitor their whole life cycle health, perform clinical cohort study, aggregate the data on platforms for big data on health and medicine, manage and provide guidance for the health status of populations, pinpoint the high-risk factors for pathogenesis, and provide effective intervention, early warning, and assessment of the vital signs of individuals, thereby reinforcing health management of the whole life cycle and safeguarding people's health in an all-round way. In addition, it drives the development of the health industry and bears strategic significance for the promotion of national economic development. It is becoming a hot research topic promising great potential and impressive applicational prospects. Herein, we reviewed new techniques for clinical saliva testing and health management based on saliva testing.

To investigate the relationship between serum C1q/tumor necrosis factor-related protein-3(CTRP3) and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) on predictive value of expression level on fracture healing.From January 2019 to January 2020, 80 patients with traumatic tibial plateau fractures were treated by internal fixation with support plates through the posterior approach of the knee joint. The patients were followed up for 12 months. According to the criteria for delayed fracture healing, the patients were divided into two groups:54 patients in fracture healing group included 24 males and 30 females, aged 29 to 75 years old with an average of (52.36±13.17) years;In the delayed healing group, there were 26 cases, 13 males and 13 females, aged from 29 to 75 with an average od (53.82±13.52) years. The serum levels of CTRP3, PGC-1αand 25 hydroxyvitamin D3[25(OH)D3] in patients with traumatic fracture were detected by enzyme-linked immunosorbent assay(ELISA);Blood phosphorus and calcium levels were measured by automatic biochemical analyzer, and the product of calcium and phosphorus was calculated;Pearson's method was used to analyze the correlation between serum CTRP3, PGC-1αand bone biochemical indexes in patients with delayed union one week after operation;The predictive value of serum levels of CTRP3 and PGC-1αon traumatic fracture healing was analyzed by receiver operating characteristic curve(ROC curve).PGC-1α, calcium phosphorus product and 25(OH)D3 in the fracture healing group were higher than those in the delayed healing group at 1 and 4 weeks after operation(The serum levels of CTRP3 and PGC-1 in patients with delayed union of traumatic fracture at 1 and 4 weeks after operation α The expression level is of certain reference value to predict the fracture healing status of patients.

Macau, Hong Kong and Singapore are all facing increasing population aging. Those aged 65 and over make up the old-age population. The working-age population refers to the population aged 15 to 64. Conventionally, the burden of population aging is measured by the Old-Age Dependency Ratio, which is the ratio of the old-age population to the working-age population. As life expectancy rises, depending exclusively on age to calculate the burden of aging hinders the development of effective anti-aging strategies. The working-age population's education and the elderly's health affect the aging burden's support and generator, respectively. Including them in the calculation gives us a fuller view of the burden of aging.ObjectiveTo compare the population aging burden in Macau, Hong Kong, and Singapore by including working-age population education and elderly health.MethodsThe overall, working-age and old-age population and proportion, as well as the Old-Age Dependency Ratio of Macau, Hong Kong, and Singapore, were collected from the World Bank database. The life expectancy at 65 was extracted from the 2022 World Population Prospect. The tertiary education rate of the working-age population and the self-rated health status of the old-age population were retrieved from governments' statistical reports. We then calculated the Education-Health Adjusted Old-Age Dependency Ratio, a set of four equations showing the support of the working-age population on the old-age population, where OADRh_t and OADRuh_t represent the burden of healthy and unhealthy old-age population on the working-age population with tertiary education; similarly, OADRh_nt and OADRuh_nt indicate the burden placed on the working-age population without tertiary education by healthy and unhealthy old-age population. Lastly, for comparison with the conventional Old-Age Dependency Ratio, we generated the Weighted Education-Health Adjusted Old-Age Dependency Ratio.ResultsHong Kong has the greatest old-age population proportion and Old-Age Dependency Ratio, yet its growth rates are moderate and stable, ranging from 0 to 4% and 0 to 6%, respectively. Macau and Singapore experienced sharper changes in old-age population proportion and the Old-Age Dependency Ratio, with Macau's Old-Age Dependency Ratio varying between −2.66 and 8.50% and Singapore's ranging from −1.53 to 9.70%. Three cities showed different patterns in four Education-Health Adjusted Old-Age Dependency Ratio indicators. In Macau, the OADRh_nt and OADRuh_nt increased by 0.4 and 6.2, while the OADRh_t and OADRuh_t decreased by 13.5 and 15.3 from 2004 to 2016. In Hong Kong, only the OADRuh_t fell by 9.4, and the other three increased from 2003 to 2015. In Singapore, the OADRh_nt and OADRh_t increased by 3.8 and 1.0, while OADRuh_nt and OADRuh_t decreased by 1.2 and 3.9 from 2007 to 2011. The Weighted Education-Health Adjusted Old-Age Dependency Ratios are all smaller than the conventional Old-Age Dependency Ratio in the three regions, particularly in Singapore. The Weighted Education-Health Adjusted Old-Age Dependency Ratio of Singapore was reduced by 9.5 to 30.5% compared with the conventional Old-Age Dependency Ratio, that of Hong Kong reduced by 6.2 to 22.5%, and that of Macau reduced by 4.4 to 16.1%.ConclusionThis is the first study to compare the aging burden in Macau, Hong Kong, and Singapore in connection to working-age population education and elderly health. With the new assessment, the burden of population aging in three regions has been reduced, showing that improving the education of the working-age population and maintaining older people's wellbeing can assist authorities to deal with population aging, especially in Macau and Hong Kong.

To analyze the salivary metabolic profile of patients with periodontitis through metabolomic techniques and to explore the metabolic patterns associated with periodontal diseases.Liquid chromatography/mass spectrometry (LC/MS) technique in conjunction with principal component analysis (PCA) analysis and orthogonal partial least squares identification (OPLS-DA) method was used to study the metabolomics of saliva samples from gingivitis patients, periodontitis patients, and healthy controls, with 10 samples for each group. We examined the correlation between migration in metabolic profile and the progression of periodontal diseases.Saliva metabolite profiles of gingivitis and periodontitis patients was significantly different from those of the healthy controls. Significant differences were identified between the different groups for eight salivary metabolites, including arachidonic acid, tyramine, L-arginine, thymine, N-acetylgalactosamine sulfate, prostaglandin E2, L-phenylalanine, and 5-aminoimidazole-4-carboxamide-riboside (AICAR). In comparison with those of the health controls, the concentration of AICAR in patients with gingivitis and periodontitis was lower and the metabolic trend was down-regulated, while the other metabolites were up-regulated.Salivary metabolic profile changes along with the progression of periodontal diseases. Abnormal metabolism of the periodontal tissue and of pathogenic microorganisms related to periodontal diseases is one of the mechanisms involved in the pathogenesis, development and prognosis of periodontal diseases.

Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

Background Emphysematous pyelonephritis (EPN) is a potentially life-threatening disease caused by a gas-producing necrotizing bacterial infection that involves the renal parenchyma, collecting system, and/or perinephric tissue. EPN is often complicated by a previous diagnosis of diabetes mellitus, and venous air bubbles are an uncommon complication of it. We describe a 52-year-old woman who was admitted in coma, with a history of vomiting, and was found to have EPN with air bubbles in the uterine veins. We discuss the presentation, diagnosis, and pathogenesis of this uncommon but clinically significant event, and briefly review other case reports of venous gas or thrombosis caused by EPN. Case presentation We report the case of a 52-year-old woman with past history of type 2 diabetes mellitus, presenting with loss of consciousness after vomiting for half a day. Abdominal computed tomography scan revealed unilateral EPN with air bubbles in the uterine veins. The blood, pus, and urine cultures were positive for extended-spectrum beta-lactamase-producing Escherichia coli. The patient’s condition improved well after conservative management comprising supportive measures, broad-spectrum antibiotics, percutaneous drainage therapy, and an open operation. Conclusions Venous air bubbles are rare but fatal complication of EPN. Early diagnosis and treatment are critical to ensure good results.

Cardiovascular disease (CVD) is a major cause of death worldwide. Research findings indicate that periodontal infection is an independent risk factor for CVD. Periodontal pathogens can cause cardiovascular diseases through various pathways, including direct invasion, induction of platelet activation and agglutination, immune inflammatory response, bacteremia, and oxidative stress. Moreover, CVD symptoms are relieved after the patients undergo periodontal interventional treatment. There have been substantial findings indicating that there may be a close connection between periodontal disease and CVD. However, periodontal disease is a chronic disease. The treatment of periodontal diseases and the improvement of periodontal health require long-term efforts. Long-term effective reduction of the incidence of CVD in clinical practice through prevention of periodontal disease remains a challenging area of study. Here we summarized and reported the latest findings on the mechanism of action of periodontal pathogens in cardiovascular diseases, intending to contribute to the better understanding of the pathogenesis of CVD and to provide potential targets and new ideas for its prevention and treatment.

BackgroundTo demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).MethodsA 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.ResultsA total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.ConclusionThe use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.Trial registration numberNCT02194634.

The thymus is the primary immune organ responsible for generating self-tolerant and immunocompetent T cells. However, the thymus gradually involutes during early life resulting in declined naïve T-cell production, a process known as age-related thymic involution. Thymic involution has many negative impacts on immune function including reduced pathogen resistance, high autoimmunity incidence, and attenuated tumor immunosurveillance. Age-related thymic involution leads to a gradual reduction in thymic cellularity and thymic stromal microenvironment disruption, including loss of definite cortical-medullary junctions, reduction of cortical thymic epithelial cells and medullary thymic epithelial cells, fibroblast expansion, and an increase in perivascular space. The compromised thymic microenvironment in aged individuals substantially disturbs thymocyte development and differentiation. Age-related thymic involution is regulated by many transcription factors, micro RNAs, growth factors, cytokines, and other factors. In this review, we summarize the current understanding of age-related thymic involution mechanisms and effects.

CD47, a transmembrane glycoprotein widely expressed on the cell surface, is one of the important checkpoints through which cells escape innate immune surveillance. The important role of CD47-related signaling pathway and changes in expression level in immune regulation, pathogen infection and anti-tumor immunity has gradually come to be recognized. We reviewed herein the structure and biological characteristics of CD47, the interaction and the downstream signaling of CD47 with integrin, thrombospondin 1, and signal regulatory protein, and the upregulated expression of CD47 induced by the infection of different pathogens and the role of CD47 in different types of immune response to infection. Discussions were made regarding the prospective application of CD47 targeted immunotherapy in pathogenic infection-related cancers, intending to provide guidance for future research.

BACKGROUND: Nipple reconstruction is widely regarded as the final step in post-mastectomy breast reconstruction. While grafts, local flaps, or combination approaches have been employed in nipple reconstruction, none has been able to achieve reliable long-term projection preservation. In response, we have sought to bioengineer neo-nipples in situ via the implantation of processed, decellularized cartilage xenografts placed within 3D-printed polylactic acid (PLA) scaffolds. MATERIALS AND METHODS: External nipple scaffolds were designed in-house and 3D-printed with PLA filament. Decellularized ovine xenograft infill was prepared and processed by mincing or zesting. All nipple scaffolds were placed subcutaneously on the dorsa of Sprague-Dawley rats and explanted after 1, 3, and 6 months for analysis. RESULTS: Explanted nipple scaffolds demonstrated gross maintenance of scaffold shape, diameter, and projection with accompanying increases in tissue volume. Histologic analyses revealed preservation of native cartilage architecture after 6 months without evidence of degradation. Analysis of formed tissue within the scaffolds revealed a progressive invasion of fibrovascular tissue with identifiable vascular channels and adipose tissue after 6 months in vivo. Confined compression testing revealed equilibrium moduli of both minced and zested samples that were within the expected range of previously reported human nipple tissue, while these data revealed no differences in the mechanical properties of the neo-tissue between time points or processing techniques. CONCLUSIONS: These preliminary data support potential use of decellularized allograft to foster healthy tissue ingrowth within a PLA scaffold, thereby offering a novel solution to current limitations in nipple reconstruction.

BACKGROUND: Reconstruction of cartilaginous deformities is a well-established surgical challenge with high levels of unpredictability and complication. Because of the morbidity associated with autologous cartilage grafting, combined with its limited supply and the significant expense of commercially decellularized allografts, increasing efforts have sought to produce an acellular, nonimmunogenic cartilage xenograft. We have developed and validated a novel protocol for high throughput decellularization of ovine costal cartilage with immediate translational potential for pre-clinical investigation of novel strategies for cartilaginous reconstruction. METHODS: Floating ribs were isolated from freshly slaughtered rack of lamb and after cleaning, the ribs were either minced into 2 mm cubes or zested into 1 mm flakes. Tissue was then decellularized via a protocol consisting of four freeze/thaw cycles, digestion with trypsin, incubation in hyperosmolar and hypo-osmolar salt solutions, with incubation in 1% Tween following both the hyperosmolar and hypo-osmolar steps, a 48-hour incubation in nucleases, DNA elution via EDTA, and two terminal sterilization steps. Protocol success was evaluated via histologic analysis with H&E, DAPI, and safranin-O staining, as well as DNA quantification. RESULTS: Histologic analysis of the decellularized tissue revealed a significant reduction in nuclei as evidenced by H&E and DAPI staining (p

Although cancer vaccines exhibit great advances in the field of immunotherapy, developing an efficient vaccine platform for personalized tumor immunotherapy is still a major challenge. Here we demonstrate that a bioactive vaccine platform (HMP@Ag) fabricated with hybrid M13 phage and personal tumor antigens can facilitate delivery of antigens into lymph nodes and activate antigen-presenting cells (APCs) through the Toll-like receptor 9 (TLR9) signaling pathway, which boosts both innate and adaptive immune response. As an adjuvant platform, hybrid M13 phages can deliver various tumor-specific antigens through simple adsorption to support the current development of personalized vaccines for cancers. Notably, the HMP@Ag vaccine not only prevented the tumors, but also delayed the tumor growth in established (subcutaneous and orthotopic) and metastatic tumor-bearing models while synergy with immune checkpoint blockade (ICB) therapy. Moreover, HMP@Ag triggered a robust neoantigen-based specific immune response in tumor-specific mutation models. In a clinically relevant surgery model, using autologous cell membrane from primary tumors-based HMP@Ag cooperation with ICB dramatically inhibited the post-operation recurrence, and elicited a long-term immune memory effect simultaneously. These findings imply that the M13 phage represents a powerful tool to develop a bio-activated hybrid platform for personalized therapy.

Conventional cancer targeting methodology needs to be reformed to overcome the intrinsic barriers responsible for poor targeting efficiency. This study describes a concept of self-reinforced cancer targeting (SRCT) by correlating targeting with therapy in a reciprocally enhancing manner. SRCT is achieved on the basis of two prerequisites: (1) target molecules have to be expressed on cancer cell membranes but not on normal cells, and (2) notably, their expression on cancer cells must be actively upregulated in response to cellular attack by cancer treatments. As a proof-of-concept, a GRP78-targeting nanovehicle for chemotherapy was designed. Resultant data showed that chemotherapeutic drugs could effectively elevate GRP78 expression on the plasma membranes of cancer cells while having minimal influence on normal cells. DOX pretreatment of cancer cells and tumor tissues can greatly increase the targeting efficacy and therapeutic performance of the prepared GRP78-targeting nanomedicine while somewhat disfavoring the nontargeting counterpart.iIn vivo/iandiin vitro/iresults demonstrated that this GRP78-targeting nanomedicine could accurately target cancer cells to not only implement chemotherapy but also induce GRP78 upregulation on cancer cells, eventually benefiting continuous cancer-cell-targeted attack by the nanomedicines remaining in the blood circulation or administered in the next dose. The GRP78-targeting nanomedicine displays much better antitumor performance compared with the nontargeting counterpart. SRCT is expected to advance cancer-targeted therapy based on the positive dependency between targeting and therapeutic modalities.

Introduction: Resurfacing complex full thickness wounds requires free tissue transfer which creates donor site morbidity. We describe a method to fabricate a skin flap equivalent with a hierarchical microvascular network. Materials & methods: We fabricated a flap of skin-like tissue containing a hierarchical vascular network by sacrificing Pluronic® F127 macrofibers and interwoven microfibers within collagen encapsulating human pericytes and fibroblasts. Channels were seeded with smooth muscle and endothelial cells. Constructs were topically seeded with keratinocytes. Results: After 28 days in culture, multiphoton microscopy revealed a hierarchical interconnected network of macro- and micro-vessels; larger vessels (>100 μm) were lined with a monolayer endothelial neointima and a subendothelial smooth muscle neomedia. Neoangiogenic sprouts formed in the collagen protodermis and pericytes self-assembled around both fabricated vessels and neoangiogenic sprouts. Conclusion: We fabricated a prevascularized scaffold containing a hierarchical 3D network of interconnected macro- and microchannels within a collagen protodermis subjacent to an overlying protoepidermis with the potential for recipient microvascular anastomosis.

Preoperative immune-nutritional status is correlated with postoperative outcomes. The Controlling Nutritional Status (CONUT) score is a useful tool for predicting the postoperative outcomes of cancer surgery. This study aimed to evaluate whether the CONUT score could predict postoperative complications in Crohn’s disease (CD) patients. In total, 202 CD patients were eligible. Univariate and multivariate analyses were performed to identify risk factors for postoperative complications. Receiver operating characteristic (ROC) curves were generated to examine the cutoff value for predictors of postoperative complications. Among all the patients, 66 developed postoperative complications. The cut-off value of the CONUT score was 3.5 for complications. Eighty-one patients had a low CONUT score ( 3.5). There was a significant difference in postoperative complications between the groups with low and high CONUT score (17.3% vs. 43.0%, p

Background Proliferative diabetic retinopathy (PDR) is one of the most common cause of vision loss in diabetic patients, and the incidence age of PDR patients gradually gets younger. This study aims to compare the characteristics of PDR and outcomes following vitrectomy in young and senior patients. Methods This is a retrospective case series study. Data of 116 eyes of 92 patients who underwent vitrectomy for PDR from February 2012 to February 2017 were reviewed, which were divided into young and senior patient groups. All patients were followed up for 24 months at least. Results There were 62.1% of eyes with tractional retinal detachment secondary to PDR in the young patient group, while only 12.1% of eyes in the senior patient group with this surgery indication. (P P = 0.085) Postoperative complications mainly included recurrent vitreous hemorrhage (24.1%), retinal detachment (3.4%), neovascular glaucoma (NVG) (27.6%) and nuclear sclerosis (53.4%) in young patients, and it was 19.0, 0.0, 1.7 and 3.4% in senior patients respectively. Conclusion PDR of young patients is more severe than that of senior patients, and vitrectomy is an effective and safe method for PDR treatment. NVG is a main and severe complication besides nuclear sclerosis in young patients, and the incidence of NVG is higher compared to that in senior patients.

Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression.

Oral cavity, an important component of and the gateway to the digestive system, is also the colonization site and the microecological environment of trillions of microorganisms. The establishment and succession of oral microbiota are of great importance for the development of human immune system, and function as a major determinant of oral and systemic health. Within a few hours after birth, early colonizers such as

Osteoarthritis (OA) is a chronic degenerative disease involving the entire joint. The pathogenesis and progression of OA bear close connection to the destruction and the abnormal metabolism of cartilage, subchondral bones and synovium. Platelet derived growth factor-AA (PDGF-AA) is a critical mitogenic and chemotactic factor for a variety of cells, including chondrocytes, mesenchymal stem cells, osteoclasts and osteoblasts, and PDGF-AA promotes effective wound repair. This paper reviewed the pathological changes of cartilage, subchondral bones and synovium in the process of OA development, and summarized research progress regarding the effect of PDGF-AA on the tissues and related cells mentioned above. Current studies have basically clarified the pathological changes of cartilage, subchondral bones and synovium in OA patients, and have shown that PDGF-AA serves critical regulatory function in the tissues or cells involved in OA, the internal mechanism of which remains unclear, though. More studies should be done to find ways to apply PDGF-AA for clinic purpose and to diagnose and treat OA on the cellular basis.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been raging across the world for over two years, but the daily reported numbers of new infections and deaths are still increasing. The newly identified Omicron variant has significant changes in its transmissibility and pathogenicity due to the multiple mutations in the spike protein, posing new challenges to the global public health. World Health Organization has categorized Omicron as a variant of concern (VOC). The spread of SARS-CoV-2 and its variants has caused disruptions to the dental practice worldwide. During the course of diagnosis and treatment of dental care, face-to-face communication at close quarters, droplets, aerosols, and exposure to saliva and blood increase the risks of SARS-CoV-2 transmission. The emergence of new variants, especially the Omicron variant, has formed new challenges to dental healthcare provision. In addition, oral tissues, including the tongue and oral mucosa, can overexpress the angiotensin converting enzyme 2 (ACE2), which is also the binding receptors of SARS-CoV-2. As a result, the oral cavity is one of the target sites of SARS-CoV-2 infection. SARS-CoV-2 infection in oral cavity may cause different oral complications, such as loss of taste. However, there are few reports about Omicron and the other variants of SARS-CoV-2 and their impacts on dental healthcare provision. Herein we made an overview of the Omicron variant and its characteristics, including its pathogenicity and immune evasion, and its potential impact on dental practice. We also proposed some control measures with the aim of reducing the possible transmission of SARS-CoV-2 and its variants during dental care.

Clinical staging, Gleason score, and prostate-specific antigen (PSA) have been accepted as factors for evaluating the prognosis of prostate cancer (PCa). With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology, we used q-Dixon magnetic resonance imaging (MRI) to measure the iron content of the PCa patients' lesions, and used enzyme-linked immunosorbent assay (ELISA) to measure the iron metabolism indicators in the patients' serum samples, combined with the patients' postoperative clinical data for analysis. We found that the serum indexes were correlated with the T2 star values, International Society of Urological Pathology (ISUP) grade, and pathological classification in PCa patients (all Plt; 0.001) but not in benign prostatic hyperplasia (BPH) patients (all Pgt; 0.05). The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH, which may be helpful for evaluating the prognosis of PCa.

The study is aimed to help promote the development of the oral healthcare system and dental public health system in China and to help achieve the goal of improving the nation's oral health. We herein provided an overview and critical evaluation of recent developments in oral healthcare systems and dental public health systems in China and other countries, and discussed a number of potential directions for the future development of dental public health. The current global public health emergency of the coronavirus disease 2019 (COVID-19) pandemic was also taken into account in our discussions. Thus, to facilitate the accomplishment of the goals of the Healthy China 2030 Program, we suggested the establishment of a community-based, prevention-oriented model for the oral healthcare system and dental public health system. The model we proposed features the integration of oral and general health services, the utilization of technological innovations and big data concerning health, and a forceful promotion of remote dental services focused on prevention and early diagnosis and treatment. Furthermore, under the background of COVID-19 becoming a normal part of people's lives, we should adopt differentiated prevention and protection measures and emergency response preplans appropriate for the actual epidemic situation of a particular region so that clinical services are strengthened while unnecessary wastes of resources are avoided. We should actively explore for alternative approaches to care in the face of special circumstances.

The proper development and the homeostasis maintenance of bones are important prerequisites for the normal functioning of the human body. Bone developmental deformities or homeostasis disorders, such as Kashin-Beck disease, craniosynostosis, cleft palate and osteoarthritis, severely affect the life of patients, causing significant stress to the family and the society. Fibroblast growth factor 8 (FGF8) plays multiple functions through the course of the life of organisms. Abnormal expression of FGF8 may cause disorders of bone homeostasis and developmental abnormalities of bones. More and more studies have found that FGF8 may play an important role in bone development and may become a potential therapeutic target. Herein, we reviewed the role of FGF8 in a variety of skeletal abnormalities, intending to provide new perspectives for the prevention and treatment of related diseases in the future.

Silk fibroin (SF) and poly vinyl alcohol (PVA)-based nanomaterial has exceptional attention in regenerative medicine. However, the preparation of SF and PVA-based nanomaterials in the desired form is complex due to their poor mechanical strength, brittleness, and compatibility. To this end, Mo

Over the past decade, there have been many studies determining the effect of dietary ω-3 and ω-6 fatty acids intake on cognitive performance; however, they have largely been inconsistent in their conclusions. In this letter, we provide context to the article by Dong et al., titled “Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011–2014” and provide methodological considerations with regards to covariate measurement and inclusion that can be generalized to future cross-sectional studies. In particular, delineating 1) the type and source of fatty acid, in context of an individual’s overall dietary patterns, 2) sociobehavioral risk factors and physical & mental comorbidities, 3) and daily cognitive activity are important to adequately control for covariates.

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sleep and neurological sensorimotor disorder. The prevalence of RLS is at ∼5-15% in the general population. RLS could severely impact the daytime work productivity and the life quality of patients. However, the current diagnostic methods fail to provide an accurate and timely diagnosis, and the pathophysiology of RLS is not fully understood. Glycomics can help to unravel the underlying biochemical mechanisms of RLS, to identify specific glycome changes, and to develop powerful biomarkers for early detection and guiding interventions. Herein, we undertook a shotgun glycomics approach to determine and characterize the potential glycan biomarker candidates in the blood serum of RLS patients. Glycan profiles and isomeric quantitations were assessed by liquid chromatography-mass spectrometry analysis and compared with healthy controls. 24

Background The aim of this study was to compare quilting suture with conventional suture on the formation of seroma at pectoral area after mastectomy (ME) with sentinel lymph nodes biopsy (SLN) or axillary lymph nodes dissection (ALND) for breast cancer. Methods Two hundred thirty-five consecutive breast cancer patients were retrospectively analyzed. The primary outcome was the incidence of Grade 2 or Grade 3 seroma at anterior pectoral area within 1 month postoperatively. We categorized seroma into early or late seroma according to the drainage removal time. Cox regression was used for analysis. Results The incidence of Grade 2 and 3 seroma was significantly higher in the conventional suture group compared with that in the quilting suture group (19.3% vs. 9.5%, p = 0.032), which was attributed to the late seroma in Grade 2 and 3. Quilting suture was associated with longer time for fixing flaps compared with that of conventional suture (504.7 s vs. 109.1 s, p Conclusions Quilting suture decreased the incidence of Grade 2 and 3 seroma at pectoral area within 1 month after mastectomy, especially the late seroma in Grade 2 and 3.

The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy., Immune checkpoint blockade (ICB) immunotherapy efficacy has still limitations. Here, the authors generate a vaccine that integrates CD274 siRNA into the L1 protein of human papillomavirus, which cooperates with ICB by activating innate immunity in breast cancer models.

Background and purpose Manual contouring is labor intensive, and subject to variations in operator knowledge, experience and technique. This work aims to develop an automated computed tomography (CT) multi-organ segmentation method for prostate cancer treatment planning. Methods and materials The proposed method exploits the superior soft-tissue information provided by synthetic MRI (sMRI) to aid the multi-organ segmentation on pelvic CT images. A cycle generative adversarial network (CycleGAN) was used to estimate sMRIs from CT images. A deep attention U-Net (DAUnet) was trained on sMRI and corresponding multi-organ contours for auto-segmentation. The deep attention strategy was introduced to identify the most relevant features to differentiate different organs. Deep supervision was incorporated into the DAUnet to enhance the features’ discriminative ability. Segmented contours of a patient were obtained by feeding CT image into the trained CycleGAN to generate sMRI, which was then fed to the trained DAUnet to generate organ contours. We trained and evaluated our model with 140 datasets from prostate patients. Results The Dice similarity coefficient and mean surface distance between our segmented and bladder, prostate, and rectum manual contours were 0.95 ± 0.03, 0.52 ± 0.22 mm; 0.87 ± 0.04, 0.93 ± 0.51 mm; and 0.89 ± 0.04, 0.92 ± 1.03 mm, respectively. Conclusion We proposed a sMRI-aided multi-organ automatic segmentation method on pelvic CT images. By integrating deep attention and deep supervision strategy, the proposed network provides accurate and consistent prostate, bladder and rectum segmentation, and has the potential to facilitate routine prostate-cancer radiotherapy treatment planning.

Liver injury is the first step in causing fibrosis, cirrhosis, and liver cancer, leading to mortality. However, the drivers of progressive liver injury are still incompletely defined. Here, we identify GBP5 as a major factor causing liver injury and inflammation. We show that the expression of GBP5 is abnormally elevated in the damaged liver, and its expression depends at least partially on the NF-κB-inducing kinase (NIK)/NF-κB2 signaling pathway. Knockout of Gbp5 ameliorates D-galactosamine/lipopolysaccharide (GalN/LPS)-induced liver injury and inflammation. Conversely, liver-specific overexpression of GBP5 induces liver injury and inflammation. Mechanistically, GBP5 induces hepatocyte apoptosis through the activation of both calpain/caspase 12/caspase 3 and TNFα/caspase 8/caspase 3 signaling pathways. Inhibition of either calpain activity or caspase 3 prevents GBP5-induced cell death. Our data demonstrate that GBP5 expression is induced by toxins or the NIK signaling pathway, which promotes both extrinsic and intrinsic apoptosis signaling pathways and further induces liver injury, providing a novel drug target for the treatment of liver injury and inflammation.

To evaluate the clinical effectiveness of Shumian capsule in improving the symptoms of insomnia, anxiety, depression, and other symptoms of convalescent patients of COVID-19.Totally 200 patients were collected and randomly divided into experiment group (n = 100) and control group (n = 100). The control group was treated with Shumian capsule simulator, and the experiment group was treated with Shumian capsule. The improvement of TCM symptom score, the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed, and the clinical effect was evaluated.One week after treatment, the scores of anxiety symptoms in the experiment group were significantly different from those in the control group (P0.05), but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group (P0.05). There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia, anxiety and depression between the experiment group and the control group (P0.05). After 2 weeks of treatment, the scores of insomnia, anxiety, depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group (P0.05). There was no significant difference in the disappearance rate of insomnia, anxiety and depression between the experiment group and the control group (P0.05). There were no significant differences in heart rate, respiration, systolic blood pressure and diastolic blood pressure between the experiment group and the control group (P0.05).Shumian capsule can significantly improve the symptoms of insomnia, anxiety and depression in COVID-19's convalescent patients with sleep and mood disorders.

To investigate the differences in the microbial floras in the urethral secretions of the patients with chronic prostatitis to provide some reliable pathogenic evidence for the diagnosis and treatment of the disease.Using high-throughput second-generation sequencing technology, we detected the microorganisms in the urethral secretions from 33 chronic prostatitis patients and 30 normal healthy males. We analyzed the significant differences in the microbial flora between the two groups via the rank-sum test and performed data processing with the bioinformatics software, P0.05 considered as with statistically significant difference.Statistically significant differences were observed in 17 kinds of bacteria from the urethral secretions between the normal healthy controls and chronic prostatitis patients. LEfSe analysis showed that the microorganisms with most significant abundance difference in the urethral secretions of the chronic prostatitis patients included micrococcaceae, coriobacteriaceae, coriobacteriales, coriobacteriia, weeksellaceae, comamonadaceae, enterobacteriaceae, enterobacteriales, xanthomonadaceae, and xanthomonadales. Principal component analysis (PCA) revealed significant difference in the microbial composition between the two groups.There is a certain correlation between chronic prostatitis and changes in the composition of urethral microbial floras. Chronic prostatitis may result from concerted action of multiple microbes rather than a single one.

Background To report on the technique and results of parallel endplate osteotomy (PEO) for severe rigid spinal deformity. Methods We retrospectively reviewed the clinical data of 36 patients with severe rigid spinal deformities who underwent PEO between July 2016 and December 2018 and who were followed up for at least 24 months. Results Following PEO, the kyphosis and scoliosis correction rates reached 77.4 ± 14.0% and 72.2 ± 18.2%, respectively. The median intraoperative estimated blood loss was 1500 mL and the median operative time was 6.8 h. The SF-36 scores of physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional and mental health changed from 62 ± 28, 51 ± 26, 49 ± 29, 35 ± 30, 53 ± 28, 45 ± 30, 32 ± 34 and 54 ± 18 at baseline to 81 ± 16, 66 ± 41, 72 ± 40, 64 ± 44, 75 ± 25, 71 ± 46, 66 ± 34 and 76 ± 28 at 12 months postoperatively, 82 ± 32, 67 ± 42, 81 ± 30, 71 ± 41, 80 ± 30, 74 ± 36, 68 ± 35 and 85 ± 33 at 18 months postoperatively, and 86 ± 21, 83 ± 33, 88 ± 26, 79 ± 39, 86 ± 36, 86 ± 48, 80 ± 47 and 91 ± 39 at 24 months postoperatively, respectively. Conclusions PEO is an effective technique for successful correction of spinal deformities. At the two-year follow-up visit, all patients achieved better clinical results based on the SF-36 scores.

Chondrocytes have a limited supply of glucose and oxygen for metabolism since articular cartilages are relatively avascular. We herein reviewed the characteristics of chondrocyte glucose metabolism and the new research progress in chondrocyte glucose metabolism in the osteoarthritis process. Current research has shown that chondrocytes obtain glucose from synovial fluids and subchondral bones, take in glucose via specific glucose transporters, and metabolize glucose mainly through glycolysis and mitochondrial respiration to produce adenosine triphosphate (ATP). Glucose metabolism in chondrocytes is distinctive because it relies much more on glycolysis rather than mitochondrial respiration for ATP production, and shows Warburg effect and Crabtree effect. In osteoarthritic chondrocytes, the glucose metabolism disorder is presented as further suppression of mitochondrial respiration, over-active or impaired glycolysis, and decreased total production of ATP. However, the significance of the glucose supply for chondrocytes from synovial fluids and subchondral bones remains undefined. There are still disputes in the understanding of the changes in glycolytic pathways in osteoarthritic chondrocytes. Therefore, future research is needed to explore the characteristics of glucose metabolism in normal and osteoarthritic chondrocytes in order to develop new diagnostic and therapeutic strategies for osteoarthritis.