Association of Maternal Mild Hypothyroidism in the First and Third Trimesters with Obstetric and Perinatal Outcomes: A Prospective Cohort Study.

BACKGROUND: Mild hypothyroidism, including subclinical hypothyroidism (SCH) and isolated maternal hypothyroxinemia (IMH), is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy. OBJECTIVE: To evaluate the impact of SCH and IMH in the first and third trimesters, respectively, on obstetric and perinatal outcomes. STUDY DESIGN: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai. 52,027 pregnant women who underwent the first-trimester antenatal screening at IPMCH were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal SCH and IMH in the first trimester on pregnancy outcomes, participants were divided into three groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n= 33,130), first-trimester SCH group (n= 884), and first-trimester IMH group (n= 846). Then, to evaluate the impact of maternal SCH and IMH in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into three groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n= 30,776), third-trimester SCH group (n= 562), and third-trimester IMH group (n= 578). Obstetric and perinatal outcomes, including preterm birth (PTB), preeclampsia, gestational hypertension, gestational diabetes mellitus (GDM), large for gestational age (LGA), small for gestational age, macrosomia, cesarean section, and fetal demise were measured and compared between those in either SCH/IMH group and euthyroid group. Binary logistic regression was used to assess the association of SCH or IMH with these outcomes. RESULTS: 34,860 pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal SCH in the first trimester was linked to a lower risk of GDM (aOR 0.64, 95% CI 0.50-0.82) compared with the euthyroid group. However, third-trimester SCH is associated with heightened rates of PTB (aOR 1.56, 95%CI 1.10-2.20), preeclampsia (aOR 2.23, 95%CI 1.44-3.45), and fetal demise (aOR 7.00, 95%CI 2.07-23.66) compared with the euthyroid group. IMH in the first trimester increased risks of preeclampsia (aOR 2.14, 95% CI 1.53-3.02), GDM (aOR 1.45, 95%CI 1.21-1.73), LGA (aOR 1.64, 95%CI 1.41-1.91), macrosomia (aOR 1.85, 95%CI 1.49-2.31) and cesarean section (aOR 1.35, 95%CI 1.06-1.74), while IMH in the third trimester increased risks of preeclampsia (aOR 2.85, 95%CI 1.97-4.12), LGA (aOR 1.49, 95%CI 1.23-1.81) and macrosomia (aOR 1.60, 95%CI 1.20-2.13) compared with the euthyroid group. CONCLUSION: This study indicates that while first-trimester SCH did not elevate the risk for adverse pregnancy outcomes, third-trimester SCH was linked to several adverse pregnancy outcomes. IMH in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.

Genomic mutation patterns and prognostic value in de novo and secondary acute myeloid leukemia: A multicenter study from China.

Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference.

Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFP@Ga-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents.

Sexual behavior and cardiovascular diseases: univariable and multivariable Mendelian randomization.

Background: To assess the relationship of genetically predicted sexual behavior (age at first sex (AFS) and the number of sexual partners (NSP)) on cardiovascular diseases (CVDs). Methods and results: We performed two-sample Mendelian randomization (MR) with publicly available datasets from the UK Biobank and FinnGen Study, and analyzed genome-wide association results for sexual behaviors and twelve types of CVDs. The univariable MR method provided a total effect of AFS and NSP on CVDs, and showed evidence that early AFS rather than NSP was associated with CVDs, including angina pectoris (AP), atrial fibrillation and flutter (AFF), coronary atherosclerosis (CAS), deep vein thrombosis of the lower extremity (DVT-LE), heart failure (HF), hypertension (HTN), ischaemic stroke (IS), and myocardial infarction (MI). Given sex as a social determinant of CVD risk, we used gender-stratified SNPs to investigate gender differences in the development of CVDs. These results showed a stronger causal relationship of AFS on CVDs in females than in males. Further multivariable MR analyses indicated a direct effect after accounting for insomnia, number of days of vigorous physical activity 10 + minutes (VPA 10 + min), and time spent watching television (TV). Two-step MR demonstrated these three risk factors act as a mediator in AFS associated AP/HTN/HF. Conclusions: We provide evidence that early AFS increased the risk of CVDs. These associations may be partly caused by VPA 10 + min, insomnia, and the time spent on TV. The causality of AFS on CVDs in females was stronger than in males. Conversely, genetically predicted NSP was not associated with CVDs.

Understanding the influencing factors and mechanism of social compensation for Chinese older adults using social media in the context of smart home: a qualitative analysis.

As a new generation of necessary terminals for future homes, smart homes have become one of the essential mediums for smart aging at home. This paper aims to explore how older adults who age at home can overcome the digital divide of the new medium and achieve social participation in the home context to realize active aging. Based on the theory of social compensation, we select the smart-home smart screen, a representative new medium product in China, and carry out open coding, spindle coding, selective coding, and theoretical construction of the original interview data through the grounded theory research method. The results show that the main factors affecting the social compensation of older adults to smart home social media include user interface quality, interaction quality, content quality, and service quality, and these four factors are used as external variables to compensate older adults socially, thereby stimulating the emotional experience and perception changes at the cognitive level of older adults and then affecting the adoption and acceptance of smart home social media by older adults. This study refines the factors influencing the older adults' use of smart home social media from the perspective of social compensation. It explains the mechanism of acceptable behavior of older adults, bridging the gap in previous literature on the influencing factors and behavioral mechanisms of older adults of smart home social media. This paper provides a theoretical basis and guidance for the subsequent academic research and software development practice of social media under new technological devices to further help older adults in China achieve active and healthy aging.

The causal association between smoking initiation, alcohol and coffee consumption, and women's reproductive health: A two-sample Mendelian randomization analysis.

Objective: A number of epidemiological studies have demonstrated that smoking initiation and alcohol and coffee consumption were closely related to women's reproductive health. However, there was still insufficient evidence supporting their direct causality effect. Methods: We utilized two-sample Mendelian randomization (TSMR) analysis with summary datasets from genome-wide association study (GWAS) to investigate the causal relationship between smoking initiation, alcohol and coffee consumption, and women's reproductive health-related traits. Exposure genetic instruments were used as variants significantly related to traits. The inverse-variance weighted (IVW) method was used as the main analysis approach, and we also performed MR-PRESSO, MR-Egger, weighted median, and weighted mode to supplement the sensitivity test. Then, the horizontal pleiotropy was detected by using MRE intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran's Q statistics. Results: We found evidence that smoking women showed a significant inverse causal association with the sex hormone-binding globulin (SHBG) levels (corrected ß = -0.033, p = 9.05E-06) and age at menopause (corrected ß = -0.477, p = 6.60E-09) and a potential positive correlation with the total testosterone (TT) levels (corrected ß = 0.033, p = 1.01E-02). In addition, there was suggestive evidence for the alcohol drinking effect on the elevated TT levels (corrected ß = 0.117, p = 5.93E-03) and earlier age at menopause (corrected ß = -0.502, p = 4.14E-02) among women, while coffee consumption might decrease the female SHBG levels (corrected ß = -0.034, p = 1.33E-03). Conclusion: Our findings suggested that smoking in women significantly decreased their SHBG concentration, promoted earlier menopause, and possibly reduced the TT levels. Alcohol drinking had a potential effect on female higher TT levels and earlier menopause, while coffee consumption might lead to lower female SHBG levels.

The early life course-related traits with three psychiatric disorders: A two-sample Mendelian randomization study.

Objectives: Several studies have indicated a potential association between early life course-related traits and neurological and psychiatric disorders in adulthood, but the causal link remains unclear. Methods: Instrumental variables (IVs) that have been shown to be strongly associated with exposure were obtained from summary data of genome-wide association studies (GWASs). Four early life course-related traits [i.e., birthweight (BW), childhood body mass index (BMI), early body size, and age at first birth (AFB)] were used as exposure IVs to estimate their causal associations with three neurological and psychiatric diseases [i.e., Alzheimer's disease (AD), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)]. Four different statistical methods, i.e., inverse-variance weighting (IVW), MR-Egger (MRE), weighted median (WM), and weighted mode (Wm), were performed in our MR analysis. Sensitivity analysis was performed by using the leave-one-out method, and horizontal pleiotropy was assessed using the MR-PRESSO package. Results: There was evidence suggesting that BW has a causal effect on AD (ORMR-PRESSO = 1.05, p = 1.14E-03), but this association was not confirmed via multivariable Mendelian randomization (MVMR) (ORMVMR = 0.97, 95% CI 0.92-1.02, p = 3.00E-01). A strong relationship was observed between childhood BMI and ADHD among both sexes; a 1-SD increase in BMI significantly predicted a 1.46-fold increase in the OR for ADHD (p = 9.13E-06). In addition, a similar relationship was found between early life body size and ADHD (ORMR-PRESSO = 1.47, p = 9.62E-05), and this effect was mainly driven by male participants (ORMR-PRESSO = 1.50, p = 1.28E-3). Earlier AFB could significantly predict a higher risk of MDD (ORMR-PRESSO = 1.19, p = 1.96E-10) and ADHD (ORMR-PRESSO = 1.45, p = 1.47E-15). No significant causal associations were observed between the remaining exposures and outcomes. Conclusion: Our results reveal the adverse effects of childhood obesity and preterm birth on the risk of ADHD later in life. The results of MVMR also show that lower BW may have no direct relationship with AD after adjusting for BMI. Furthermore, AFB may predict a higher risk of MDD.

"Simulation of medical goggles to stop airborne transmission of viruses: computational fluid dynamics in ergonomics".

This paper presents a position statement on combining computational fluid dynamics (CFD) and ergonomics to guide the design of personal protective equipment (PPE). We used CFD to simulate 36 exposure scenarios of an infected patient sneezing at different distances and different angles while facing either the front or the side of a healthcare worker with or without goggles. The results show that medical goggles indeed block most droplets from the outer surface, but many droplets still deposit on the bottom edge (especially at the nose), inside the air holes and on the side edge. However, the edges of medical goggles have fitment problems with people in different regions, and the air holes do not function as filters and cannot prevent fine droplets from entering the interior and contacting the eyes. Our research demonstrates the feasibility of studying the design of PPE for airtightness and protection by means of CFD.Practitioner summary: Computational fluid dynamics can quickly and efficiently reflect the airtightness design problems of PPE. A model was developed using CFD to examine the protective effect of medical goggles in preventing the airborne transmission of viruses. The model demonstrates the feasibility of using CFD to solve ergonomic problems.Abbreviations: CFD: computational fluid dynamics; PPE: personal protective equipment; WHO: the World Health Organisation; COVID-19: coronavirus disease 2019; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; OSHA: the Occupational Safety and Health Administration; CDC: the Centres for Disease Control; FEM: finite element method; 3M: Minnesota Mining and Manufacturing Corporation; SPH: smoothed particle hydrodynamics; AROM: active range of motion; DPM: discrete phase model; PISO: pressure implicit with splitting of operators; VR: virtual reality; AR: augmented reality.

Pressure sensitivity for head, face and neck in relation to soft tissue.

Pressure sensitivity research on the head, face, and neck is critical to develop ways to reduce discomfort caused by pressure in head-related products. The aim of this paper is to provide information for designers to be able to reduce the pressure discomfort by studying the relation between pressure sensitivity and soft tissue in the head, face and neck. We collected pressure discomfort threshold (PDT) and pressure pain threshold (PPT) from 119 landmarks (unilateral) for 36 Chinese subjects. Moreover, soft tissue thickness data on the head, face and neck regions of 50 Chinese people was obtained through CT scanning while tissue deformation data under the PDT and PPT states was obtained from literature. The results of the three-elements correlation analysis revealed that soft tissue thickness is positively correlated with deformation but not an important factor in pressure sensitivity. Our high-precision pressure sensitivity maps confirm earlier findings of more rough pressure sensitivity studies, while also revealing additional fine scale sensitivity differences. Finally, based on the findings, a high-precision "recommended map" of the optimal stress-bearing area of the head, face and neck was generated.

The Causal Evidence of Birth Weight and Female-Related Traits and Diseases: A Two-Sample Mendelian Randomization Analysis.

Objectives : A large meta-analysis indicated a more pronounced association between lower birth weight (BW) and diseases in women but less concern about the causality between BW and female-related phenotypes and diseases. Methods: Mendelian randomization (MR) analysis was used to estimate the causal relationship between two traits or diseases using summary datasets from genome-wide association studies. Exposure instrumental variables are variants that are strongly associated with traits and are tested using four different statistical methods, including the inverse variance weighting, MR-Egger, weighted median, and weighted mode in MR analysis. Next, sensitivity analysis and horizontal pleiotropy were assessed using leave-one-out and MR-PRESSO packages. Results: The body mass index (BMI) in adulthood was determined by BW (corrected ß = 0.071, p = 3.19E-03). Lower BW could decrease the adult sex hormone-binding globulin (SHBG) level (ß = -0.081, p = 2.08E-06), but it resulted in increased levels of bioavailable testosterone (bio-T) (ß = 0.105, p = 1.25E-05). A potential inverse effect was observed between BW and menarche (corrected ß = -0.048, p = 4.75E-03), and no causal association was confirmed between BW and the risk of endometriosis, leiomyoma, and polycystic ovary syndrome. Conclusion: Our results suggest that BW may play an important role and demonstrates a significant direct influence on female BMI, SHBG and bio-T levels, and menarche.

Icariin-loaded sulfonated polyetheretherketone with osteogenesis promotion and osteoclastogenesis inhibition properties via immunomodulation for advanced osseointegration.

Preventing prosthesis loosening due to insufficient osseointegration is critical for patients with osteoporosis. Endowing implants with immunomodulatory function can effectively enhance osseointegration. In this work, we loaded icariin (ICA) onto 3D porous sulfonated PEEK (SPEEK) via polydopamine (PDA) modification. Modified ICA-PDA@SPEEK not only promoted the polarization of macrophages to the anti-inflammatory M2 type, but also enhanced the osteogenesis of bone mesenchymal stem cells (BMSCs) and inhibited RANKL-induced osteoclastogenesis by regulating cytokine from macrophages. In vivo experiments further showed that ICA-PDA@SPEEK regulated the host immune response and promoted osseointegration in ovariectomized (OVX) rats. The above results demonstrated that ICA-PDA@SPEEK could be an excellent orthopedic biomaterial with immunomodulatory properties.

Developmental origins of adult diseases.

The occurrence and mechanisms of developmental adult diseases have gradually attracted attention in recent years. Exposure of gametes and embryos to adverse environments, especially during plastic development, can alter the expression of certain tissue-specific genes, leading to increased susceptibility to certain diseases in adulthood, such as diabetes, cardiovascular disease, neuropsychiatric, and reproductive system diseases, etc. The occurrence of chronic disease in adulthood is partly due to genetic factors, and the remaining risk is partly due to environmental-dependent epigenetic information alteration, including DNA methylation, histone modifications, and noncoding RNAs. Changes in this epigenetic information potentially damage our health, which has also been supported by numerous epidemiological and animal studies in recent years. Environmental factors functionally affect embryo development through epimutation, transmitting diseases to offspring and even later generations. This review mainly elaborated on the concept of developmental origins of adult diseases, and revealed the epigenetic mechanisms underlying these events, discussed the theoretical basis for the prevention and treatment of related diseases.

Establishment of a finite element model based on craniofacial soft tissue thickness measurements and stress analysis of medical goggles.

In this study, an accurate finite element (FE) stress analysis of head-mounted products for Chinese users was performed. Using craniofacial computed tomography scans of 280 Chinese individuals, the total soft tissue thickness and thickness of the fat and muscle layers for 41 landmarks were measured. The data were used to construct FE head models (FEH). An FE stress test was conducted to analyse the wearing of medical goggles using two FE models based on one-layer (FEH 1) and three-layer (FEH 3) soft tissue material parameters. When compared with the experimental results, the modelling results for FEH 3 were more realistic than those for FEH 1. Wearing medical goggles led to stress concentration over five landmark areas, A: upper medial forehead, B: temporal, C: zygion, D: infraorbital fossa and E: rhinion, of which B, C and D caused the most discomfort during long-term goggle wear. Practitioner summary: A precise FE head model can reflect the complex contact pressure of a head-related product. Two FE models based on one- and three-layer soft tissue material parameters were established and tested separately with medical goggles. The model can be used to improve the comfort of head-related products. Abbreviations: FE: finite element; FEH: FE head models; FEH 1: FE models based on one-layer; FEH 3: FE models based on three-layer; VR: virtual reality; AR: augmented reality; 3D: three-dimensional; WSU: Wayne State University; WSUBIM: Wayne State University Brain Injury Model; CT: computed tomography; MRI: magnetic resonance imaging; CFSTT: craniofacial soft tissue thickness; FSR: force sensing resistor; NURBS: non-uniform rational basis spline; SPSS: statistical product and service solutions; STL: stereolithography; STP: standard for the exchange of product model data; BDF: glyph bitmap distribution format; EEG: electroencephalogram.

Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

BACKGROUND: Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. RESULTS: Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. CONCLUSION: Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.

Congener-Induced Sulfur-Related Metabolism Interference Therapy Promoted by Photothermal Sensitization for Combating Bacteria.

Metabolic homeostasis is vital for individual cells to keep alive. Stronger metabolic homeostasis allows bacteria to survive in vivo and do persistent harm to hosts, which is especially typical in implant-associated infection (IAI) with biofilm intervention. Herein, based on the competitive role of selenium (Se) and sulfur (S) in bacteria metabolism as congeners, a congener-induced sulfur-related metabolism interference therapy (SMIT) eradicating IAI is proposed by specific destruction of bacteria metabolic homeostasis. The original nanodrug manganese diselenide (MnSe2 ) is devised to generate permeable H2 Se in bacteria, triggered by the acidic microenvironment. H2 Se, the congener substitution of H2 S, as a bacteria-specific intermediate metabolite, can embed itself into the H2 S-utilization pathway and further alternatively disrupt the downstream sulfur-related metabolism state inside bacteria. A proteomic study indicates ribosome-related proteins are heavily downregulated and the basic metabolic pathways are mainly disordered after SMIT, revealing the destruction of bacteria metabolic homeostasis. The efficiency of SMIT is significantly promoted with the mild temperature sensitization provided by the photothermal treatment (PTT) of MnSe2 nanoparticles, verified by the proteomic study and the anti-IAI effect in vitro and in vivo. With the intelligent nanodrug, a PTT-promoted SMIT strategy against IAI is provided and a new insight into the interference design toward metabolic homeostasis with biochemical similarity is demonstrated.

Age- and Sex-Related Measurements of Total Craniofacial Soft Tissue Thickness and Fat in a Central Chinese Population.

ABSTRACT: In this study, data related to the total soft tissue thickness and fat layer thickness of 41 anatomical landmarks were extracted from the craniofacial computerized tomography data of 280 Chinese individuals (160 males and 120 females). The measurements were assessed according to the following factors: a. sex, b. age, and c. sex × age. Descriptive statistics and a differential analysis were carried out in each group to analyze both the total soft tissue thickness and fat layer thickness. The results showed the following. 1. The results showed that the greater the total thickness of the soft tissue, the thicker the fat layer. 2. The thicknesses of the head and face soft tissues are strongly affected by sex. The total thickness of all landmark points in the men, except for the zygomatic points, was on average greater than that in the women. In contrast to the total thickness, the fat layer, except for the point of rhinion, in the women was larger than that in the men. 3. In the comparison of the 4 age groups, most feature points did not show an evident increasing or decreasing trend with age in the total thickness of the soft tissue. However, regarding the thickness of fat, the thickness at the other points, except for the feature infraorbital fossa point, decreased with age. 4. In the analysis of the sex × age group, no statistically significant differences were found at any landmark points. This paper is significant for facial reconstruction and cosmetic surgery in the Chinese population.

Better choice of the type of specimen used for untargeted metagenomic sequencing in the diagnosis of periprosthetic joint infections.

AIMS: As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. METHODS: In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases). RESULTS: The sensitivity and specificity of mNGS in the diagnosis of PJI were 95% and 94.7%, respectively, for all types of specimen. The sensitivity and specificity were 65% and 100%, respectively, for periprosthetic tissues, 87.5% and 94.7%, respectively, for synovial fluid, and 92.5% and 94.7%, respectively, for prosthetic sonicate fluid. The mNGS of prosthetic sonicate fluid outperformed that for other types of specimen in the rates of detection of pathogens (84.6%), sequencing reads (> ten-fold) and the rate of genome coverage (> five-fold). CONCLUSION: mNGS could serve as an accurate diagnostic tool in the detection of pathogens in patients with a PJI using three types of specimen. Due to its superior perfomance in identifying a pathogen, mNGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests such as bacteriological culture in these patients. Cite this article: Bone Joint J 2021;103-B(5):923-930.

Space-Selective Chemodynamic Therapy of CuFe5O8 Nanocubes for Implant-Related Infections.

Implant-related infections (IRIs) are a serious complication after orthopedic surgery, especially when a biofilm develops and establishes physical and chemical barriers protecting bacteria from antibiotics and the hosts local immune system. Effectively eliminating biofilms is essential but difficult, as it requires not only breaking the physical barrier but also changing the chemical barrier that induces an immunosuppressive microenvironment. Herein, tailored to a biofilm microenvironment (BME), we proposed a space-selective chemodynamic therapy (CDT) strategy to combat IRIs using metastable CuFe5O8 nanocubes (NCs) as smart Fenton-like reaction catalysts whose activity can be regulated by pH and H2O2 concentration. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by CuFe5O8 NCs, thereby disrupting the rigid biofilm. Outside the biofilm with relatively higher pH and lower H2O2 concentration, lower levels of generated •OH effectively reversed the immunosuppressive microenvironment by inducing pro-inflammatory macrophage polarization. Biofilm fragments and exposed bacteria were then persistently eliminated through the collaboration of pro-inflammatory immunity and •OH. The spatially selective activation of CDT and synergistic immunomodulation exerted excellent effects on the treatment of IRIs in vitro and in vivo. The anti-infection strategy is expected to provide a method to conquer IRIs.