Search

Abstract The colonization of alien plants in new habitats is typically facilitated by microorganisms present in the soil environment. However, the diversity and structure of the archaeal, bacterial, and fungal communities in the latitudinal spread of alien plants remain unclear. In this study, the rhizosphere and bulk soil of Chromolaena odorata were collected from five latitudes in Pu’ er city, Yunnan Province, followed by amplicon sequencing of the soil archaeal, bacterial, and fungal communities. Alpha and beta diversity results revealed that the richness indices and the structures of the archaeal, bacterial, and fungal communities significantly differed along the latitudinal gradient. Additionally, significant differences were observed in the bacterial Shannon index, as well as in the structures of the bacterial and fungal communities between the rhizosphere and bulk soils. Due to the small spatial scale, trends of latitudinal variation in the archaeal, bacterial, and fungal communities were not pronounced. Total potassium, total phosphorus, available nitrogen, available potassium and total nitrogen were the important driving factors affecting the soil microbial community structure. Compared with those in bulk soil, co-occurrence networks in rhizosphere microbial networks presented lower complexity but greater modularity and positive connections. Among the main functional fungi, arbuscular mycorrhizae and soil saprotrophs were more abundant in the bulk soil. The significant differences in the soil microbes between rhizosphere and bulk soils further underscore the impact of C. odorata invasion on soil environments. The significant differences in the soil microbiota along latitudinal gradients, along with specific driving factors, demonstrate distinct nutrient preferences among archaea, bacteria, and fungi and indicate complex microbial responses to soil nutrient elements following the invasion of C. odorata.

Abstract Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

Summary: The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and

Abstract We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Abstract Background Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. Results We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to “generalists.” Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. Conclusions These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract

The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae (Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae (R. barbariae) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae. All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.

Abstract Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due to the delayed apoptosis process in aging‐related diseases, such as osteoarthritis (OA). In this study, cartilage lesion‐localized hydrogel microspheres are developed to remodel the in situ efferocytosis to reverse cartilage senescence and recruit endogenous stem cells to accelerate cartilage repair. Specifically, aldehyde‐ and methacrylic anhydride (MA)‐modified hyaluronic acid hydrogel microspheres (AHM), loaded with pro‐apoptotic liposomes (liposomes encapsulating ABT263, A‐Lipo) and PDGF‐BB, namely A‐Lipo/PAHM, are prepared by microfluidic and photo‐cross‐linking techniques. By a degraded porcine cartilage explant OA model, the in situ cartilage lesion location experiment illustrated that aldehyde‐functionalized microspheres promote affinity for degraded cartilage. In vitro data showed that A‐Lipo induced apoptosis of senescent chondrocytes (Sn‐chondrocytes), which can then be phagocytosed by the efferocytosis of macrophages, and remodeling efferocytosis facilitated the protection of normal chondrocytes and maintained the chondrogenic differentiation capacity of MSCs. In vivo experiments confirmed that hydrogel microspheres localized to cartilage lesion reversed cartilage senescence and promoted cartilage repair in OA. It is believed this in situ efferocytosis remodeling strategy can be of great significance for tissue regeneration in aging‐related diseases.

Soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with worldwide distributions. As one representative group of Argasidae, the genus Argas has an important vectorial role in transmitting zoonotic diseases. However, our knowledge of the subgenus Argas in China is still limited, as most literature only lists occurrence records or describes specific case reports without providing detailed morphological characteristics and further molecular data. This study aims to characterize Argas vulgaris through complete mitochondrial sequencing and morphological diagnostic techniques based on a batch of adult specimens collected from Ningxia Hui Autonomous Regions (NXHAR), North China. The morphology and microstructures of Ar. vulgaris and other lectotypes of argasid ticks in the subgenus Argas were also observed using a stereomicroscope. Following DNA extraction and sequencing, a complete mitochondrial sequence of Ar. vulgaris was assembled and analyzed within a phylogenetic context. The 14,479 bp mitogenome of Ar. vulgaris consists of 37 genes, including 13 genes for protein coding, two for ribosomal RNA, 22 for transfer RNA, and one for control region (D-loops). Phylogenetic analysis of Ar. vulgaris showed 98.27%–100% nucleotide identity with Ar. japonicus, indicating a close relationship between the two tick species. The morphological diagnostic features to differentiate Ar. vulgaris from other ticks within the subgenus Argas included the location of the anus and setae on the anterior lip of the female genital aperture. This study provided high-resolution scanning electron microscope images of female Ar. vulgaris and corresponding molecular data, representing valuable resources for future accurate species identification.

BackgroundCarotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function’s impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated.MethodsIn this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis.ResultsThe study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT.ConclusionThis research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

Abstract Background Human babesiosis is a worldwide disease caused by intraerythrocytic protozoa of the genus Babesia. It is transmitted by bites from ixodid ticks, and mechanically transmitted by blood transfusion. It is primarily treated with quinine and/or atovaquone, which are not readily available in China. In this study, we developed a novel treatment regimen involving doxycycline monotherapy in a patient with severe Babesia venatorum infection as an alternative therapeutic medication. The aim of our study is to provide a guidance for clinical practice treatment of human babesiosis. Case presentation A 73-year-old man who had undergone splenectomy and blood transfusion 8 years prior, presented with an unexplained fever, headache, and thrombocytopenia, and was admitted to the Fifth Medical Center of the PLA General Hospital. He was diagnosed with B. venatorum infection by morphological review of thin peripheral blood smears, which was confirmed by multi-gene polymerase chain reaction (PCR), and sequencing of the entire 18s rRNA and partial β-tubulin encoding genes, as well as isolation by animal inoculation. The doxycycline monotherapy regimen (peros, 0.1 g bisindie) was administered following pharmacological guidance and an effective outcome was observed. The patient recovered rapidly following the doxycycline monotherapy. The protozoan load in peripheral blood samples decreased by 88% in hematocrit counts after 8 days, and negative PCR results were obtained after 90 days of follow-up at the hospital. The treatment lasted for 3 months without any side effects or sequelae. The nine-month follow-up survey of the patient did not reveal any signs of recrudescence or anti-babesial tolerance. Conclusions We have reported a clinical case of successful doxycycline monotherapy for human babesiosis caused by B. venatorum, which provides an optional medical intervention for human babesiosis. Graphical Abstract

Abstract Background With its high nutritional value and productivity, Italian ryegrass as a biomass feedstock constantly supplies rumen degradable nitrogen and digestible fiber to ruminants. However, biofuel production is easily reduced during ensiling due to the high-moisture content of Italian ryegrass, leading to economic losses. Lactic acid bacteria inoculants could improve lignocellulosic degradation and fermentation quality and decrease dry matter loss during the bioprocessing of silage. Therefore, this study analyzed the effects of Lactobacillus buchneri TSy1-3 (HE), Lactobacillus rhamnosus BDy3-10 (HO), and the combination of HE and HO (M) on fermentation quality, bacterial community and metabolome in high-moisture Italian ryegrass silage during ensiling. Results The results showed that the pH value was significantly lower in the HO groups than in the other treatments at the end of ensiling, and the dry matter and acetic acid contents were significantly higher in the HO group than in the other inoculated groups. All inoculants decreased the diversity of the bacterial community and significantly increased the relative abundance of Lactobacillus. Inoculation with HO significantly improved the concentrations of organic acids, dipeptides, ferulic acid, apigenin, and laricitrin. Compared with Lactobacillus buchneri TSy1-3 (HE), HO significantly upregulated the flavonoid compounds in the flavone and flavonol biosynthesis pathway. Conclusions Overall, these findings suggest that inoculation with HO was beneficial for the development of Italian ryegrass as a biomass feedstock, improving fermentation quality, accelerating changes in bacterial community composition and increasing biofunctional metabolites in high-moisture Italian ryegrass silage.

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF.Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the “no-use of OACs” using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire.Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as “underdosing-use of OACs,” 134 (25%) who needed anticoagulation therapy were “no-use of OACs” and eight (1.5%) were “over-use of OACs.” The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57–13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11–3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67–17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44–7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11–2.35) were associated with “no-use of OACs” in patients with NVAF who had indications for anticoagulation therapy.Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient’s needs.

Abstract Background The impact of host skin microbiome on horizontal transmission of tick-borne pathogens , and of pathogen associated transstadial and transovarial changes in tick microbiome are largely unknown, but are important to control increasingly emerging tick-borne diseases worldwide. Methods Focusing on a rickettsiosis pathogen, Rickettsia raoultii, we used R. raoultii-positive and R. raoultii-negative Dermacentor spp. tick colonies to study the involvement of skin microbiota in cutaneous infection with rickettsiae in laboratory mice, and the function of the tick microbiome on maintenance of rickettsiae through all tick developmental stages (eggs, larvae, nymphs, adults) over two generations. Results We observed changes in the skin bacteria community, such as Chlamydia, not only associated with rickettsial colonization but also with tick feeding on skin. The diversity of skin microbiome differed between paired tick-bitten and un-bitten sites. For vertical transmission, significant differences in the tick microbiota between pathogenic rickettsia-positive and -negative tick chorts was observed across all developmental stages at least over two generations, which appeared to be a common pattern not only for R. raoultii but also for another pathogenic species, Candidatus Rickettsia tarasevichiae. More importantly, bacterial differences were complemented by functional shifts primed for genetic information processing during blood feeding. Specifically, the differences in tick microbiome gene repertoire between pathogenic Rickettsia-positive and -negative progenies were enriched in pathways associated with metabolism and hormone signals during vertical transmission. Conclusions We demonstrate that host skin microbiome might be a new factor determining the transmission of rickettsial pathogens through ticks. While pathogenic rickettsiae infect vertebrate hosts during blood-feeding by the tick, they may also manipulate the maturation of the tick through changing the functional potential of its microbiota over the tick’s life stages. The findings here might spur the development of new-generation control methods for ticks and tick-borne pathogens. Video Abstract

Abstract Background This study explored the impact of MTM service on MMD patients with hypertension. Methods A total of 120 MMD inpatients from September to November 2019 were received and randomly divided into intervention group and control group. General services for noninfectious chronic diseases were given to the control group, while a standard MTM service was given to the intervention group. Patients’ blood pressure, EQ-5D utility value, readmission rate, drug-related problems, and average daily medication therapy cost were compared between the two groups and within the groups. This was done at the initial admission phase and in the first, third, sixth, and twelfth months after discharge. Results The intervention group had significantly lower blood pressure and average daily medication therapy cost 12 months after discharge compared to the control group (systolic blood pressure: P = 0.023, diastolic blood pressure: P 0.05). Conclusions MTM implementation in MMD patients can improve health outcomes and reduce healthcare-related costs among MMD patients. Trial registration Chinese Clinical Trial Register ChiCTR2200065111, date of registration: October 28, 2022.

ABSTRACT Theileria, a tick-borne intracellular protozoan, can cause infections of various livestock and wildlife around the world, posing a threat to veterinary health. Although more and more Theileria species have been identified, genomes have been available only from four Theileria species to date. Here, we assembled a whole genome of Theileria luwenshuni, an emerging Theileria, through next-generation sequencing of purified erythrocytes from the blood of a naturally infected goat. We designated it T. luwenshuni str. Cheeloo because its genome was assembled by the researchers at Cheeloo College of Medicine, Shandong University, China. The genome of T. lunwenshuni str. Cheeloo was the smallest in comparison with the other four Theileria species. T. luwenshuni str. Cheeloo possessed the fewest gene gains and gene family expansion. The protein count of each category was always comparable between T. luwenshuni str. Cheeloo and T. orientalis str. Shintoku in the Eukaryote Orthologs annotation, though there were remarkable differences in genome size. T. luwenshuni str. Cheeloo had lower counts than the other four Theileria species in most categories at level 3 of Gene Ontology annotation. Kyoto Encyclopedia of Genes and Genomes annotation revealed a loss of the c-Myb in T. luwenshuni str. Cheeloo. The infection rate of T. luwenshuni str. Cheeloo was up to 81.5% in a total of 54 goats from three flocks. The phylogenetic analyses based on both 18S rRNA and cox1 genes indicated that T. luwenshuni had relatively low diversity. The first characterization of the T. luwenshuni genome will promote better understanding of the emerging Theileria. IMPORTANCE Theileria has led to substantial economic losses in animal husbandry. Whole-genome sequencing data of the genus Theileria are currently limited, which has prohibited us from further understanding their molecular features. This work depicted whole-genome sequences of T. luwenshuni str. Cheeloo, an emerging Theileria species, and reported a high prevalence of T. luwenshuni str. Cheeloo infection in goats. The first assembly and characterization of T. luwenshuni genome will benefit exploring the infective and pathogenic mechanisms of the emerging Theileria to provide scientific basis for future control strategies of theileriosis.

Abstract Background Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. Methods Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, β-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. Results Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent β-catenin stabilization and nuclear translocation. Nuclear β-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. Conclusions This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract

Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wide range of medical fields, especially the cartilage tissue engineering (TE). Notably, microcarrier systems provide an attractive method for regulating cell phenotype and microtissue maturations, they also serve as powerful injectable carriers and are combined with new technologies for cartilage regeneration. In this review, we introduced the typical methods to fabricate various types of microcarriers and discussed the appropriate materials for microcarriers. Furthermore, we highlighted recent progress of applications and general design principle for microcarriers. Finally, we summarized the current challenges and promising prospects of microcarrier-based systems for medical applications. Overall, this review provides comprehensive and systematic guidelines for the rational design and applications of microcarriers in cartilage TE.

Neural tissue engineering (NTE) has made remarkable strides in recent years and holds great promise for treating several devastating neurological disorders. Selecting optimal scaffolding material is crucial for NET design strategies that enable neural and non-neural cell differentiation and axonal growth. Collagen is extensively employed in NTE applications due to the inherent resistance of the nervous system against regeneration, functionalized with neurotrophic factors, antagonists of neural growth inhibitors, and other neural growth-promoting agents. Recent advancements in integrating collagen with manufacturing strategies, such as scaffolding, electrospinning, and 3D bioprinting, provide localized trophic support, guide cell alignment, and protect neural cells from immune activity. This review categorises and analyses collagen-based processing techniques investigated for neural-specific applications, highlighting their strengths and weaknesses in repair, regeneration, and recovery. We also evaluate the potential prospects and challenges of using collagen-based biomaterials in NTE. Overall, this review offers a comprehensive and systematic framework for the rational evaluation and applications of collagen in NTE.

Silage can be contaminated with mycotoxins and accidental fungi after aerobic exposure. The study assessed the effects of bunker silos (BS), round bales (RB), and silage bags (SB) on the nutritional characteristics, fermentation quality, aerobic stability, mycotoxin levels and microbial communities of whole-plant corn silage (WPCS). After 90 days of fermentation, silages were opened and sampled at 0, 1, 3, 5, 7, and 9 days of exposure. SB group conserved higher lactic acid and dry matter contents and a lower pH value than other groups after 9 days of exposure (p

Category: Hindfoot; Ankle Introduction/Purpose: Weight Bearing CT (WBCT) has been proven to be effective in hindfoot alignment assessment. However, we have noted that in both WBCT examination and evaluation, positioning of the foot has not been sufficiently prioritized. We hypothesized that changing the foot orientation will significantly affect the measurement of the hindfoot, which will in turn affect further clinical decision making. Methods: WBCT scans of ten feet without any foot and ankle deformity were loaded in CubeVue software. The foot was aligned to a neutral (0°) position based on the 2nd ray and the heel, and was then rotated 5°, 10°, 15° and 20° both externally and internally to simulate malposition. The 'semi' three dimensional hindfoot Moment Arm (HMA) was evaluated with the foot in these different positions. For measured parameters, varus alignment was recorded as a negative value, and valgus alignment was recorded as a positive value. Each measurement was repeated twice to minimize bias. A linear regression model was used to analyze the relationship of the HMA value and the rotation angles. An intraclass correlation coefficient (ICC) model was used to assess the intra- and interobserver reliability. Statistical analysis was completed using SAS 9.4. Results: When rotating the foot from external 20° to internal 20°, the HMA demonstrated a linear change in hindfoot alignment from varus to valgus. A 1° increase in the rotation angle caused 0.52 (±0.03) mm increase in the HMA value (Figure 1). The HMA measurements had excellent inter- and intra-observer reliability (ICC >= 0.9) (Table 1). Both CT images and measured values confirmed that internal rotation changed a neutral into a valgus hindfoot, and external rotation changed a neutral hindfoot into varus (Figure 2). Conclusion: When using current two or 'semi' three-dimensional methods to evaluate hindfoot alignment on WBCT scans, positioning the foot in the correct orientation is critical. Malrotation and malposition of the foot will cause significant impact on measurements and generate false data as well as misdiagnoses. This study was performed on normal feet but is clinically relevant when applied to deformities, particularly those associated with abduction or adduction of the midfoot and forefoot while current knowledge about deformed foot positioning is limited. This is an important topic for future investigation.

Category: Hindfoot; Other Introduction/Purpose: Radiographic characteristics of Müller-Weiss disease (MWD) include compression and flattening of the lateral one-third of the tarsal navicular, lateral and inferior the shift of the talar head, followed by a varus hindfoot which produces a paradoxical planovarus. The radiographic Stage of the disease has no direct correlation with symptoms and therefore X-ray and CT have limitations in the surgical decision making for treatment. This study aimed to determine the predictive value of the use of SPECT-CT in surgical decision making. We hypothesized that SPECT-CT will highlight the specific joints actively involved in the disease process, and with the correct selective arthrodeses as well as intraoperative correction of malalignment of the hind and midfoot, improved clinical outcomes can be achieved. Methods: This was an IRB approved prospective study with 24 MWD patients (25 feet) enrolled. All patients failed conservative treatment and agreed to undergo SPECT-CT examination for further diagnostic purposes. The SPECT-CT scans were evaluated to identify the joints that were actively involved. Weightbearing X-rays (WBXR) and weightbearing CT scans (WBCT) were performed to assess the pre and postoperative midfoot and hindfoot alignment, including the talo-first metatarsal angle (TFMA), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA), the Tomeno-Méary angle (TMA) and calcaneal pitch angle (CPA), and the hindfoot alignment angle (HAA). The surgical plan was based on the SPECT-CT and included guided arthrodesis, correction of hindfoot varus, talonavicular subluxation, and restoration of the medial arch. The AOFAS midfoot scale, visual analog scale (VAS), Foot and Ankle Ability Measure (FAAM) Sports subscale, and the 36-Item Short Form Health Survey (SF-36) were used pre and postoperatively to evaluate the clinical outcomes. Results: There were 20 females and 4 males with a mean age of 57.2 years and a mean duration of symptoms of 5.24 years. According to the Maceira staging system, there were 2 stage II, 8 stage III, 13 stage IV and 2 stage V. Three feet received isolated talonavicular arthrodesis, a talonavicular-cuneiform arthrodesis (10), triple arthrodesis (9), and triple plus navicular-cuneiform arthrodesis (3). The median follow-up time was 53.5 (range, 20-91) months. There were statistically significant improvements in the midfoot and hindfoot alignments (TNCA, TMA, CPA, HAA) and patient reported outcome measure scores (AOFAS, VAS, SF- 36 PF, SF-36 BP). Six patients required additional surgery (3 for hardware removal, and 3 for nonunion). No patient required revision surgery for arthritic pain in adjacent joints. Conclusion: SPECT-CT guided selective arthrodesis and correction of midfoot and hindfoot alignment can achieve both satisfactory clinical and radiographic outcomes in treating different stages of MWD. SPECT-CT is a very helpful tool to identify actively involved joints with arthritis secondary to the malalignment associated with this disease process, and avoids unnecessary arthrodesis of joints not actively involved in the disease process.

Category: Hindfoot; Ankle Introduction/Purpose: The Hindfoot Moment Arm (HMA) has been used to evaluate the hindfoot alignment with the Saltzman weightbearing XRay images (1), and was recently introduced into the field of weightbearing CT (WBCT) by Saltzman et al (2). The authors of this study have noticed that when using the Saltzman WBCT HMA technique, it is very difficult to determine the specific 'one' image in coronal plane scans with the widest tibial diaphyseal to draw the long axis of the tibia. The purpose of this study was to introduce a modified technique of measuring HMA in WBCT scans and compare the inter and intra-observer reliabilities between the modified and the Saltzman WBCT HMA techniques. Methods: WBCT scans of ten healthy limbs were loaded in CubeVue software. The foot was aligned in the correct orientation in the transverse plane based on the 2nd ray and the heel and the HMA was evaluated using the modified and Saltzman techniques. Using the modified technique, the sagittal plane thickness of one scan cut was increased to include the full width and length of the tibia and the axis of the distal tibia was identified by connecting two circles tangential to both cortices of the tibia. The weightbearing point of the calcaneus was located and the HMA was evaluated by measuring the perpendicular distance of the calcaneus weightbearing point to the axis of the distal tibia with varus a negative and valgus alignment a positive value. Intraclass correlation coefficient (ICC) model was used to assess the intra- and interobserver reliability of the two HMA techniques in SAS 9.4. Results: Both techniques had excellent intra- and interobserver reliability (Saltzman WBCT HMA intra-observer ICC=0.97, Saltzman WBCT HMA inter-observer ICC=0.94, the modified WBCT HMA intra-observer ICC=0.99, the modified WBCT HMA inter-observer ICC=0.91) (Table 1). Conclusion: The modified WBCT HMA was equivalent to the Saltzman technique in both inter and intra-observer reliabilities. The authors found that the modified technique was easier and less time consuming to perform in identifying the axis of the tibia since the modified technique uses multiple cuts to restore the full thickness of tibia, which not only reduces potential error, but also saves time during measurements. Compared with a relatively shorter tibia in one cut, the reconstructed tibia provides a longer and clearer shaft to work with, which allows both proximal and distal circles to be drawn with higher precision (Figure 1). 1. Saltzman, C. L., & El-Khoury, G. Y. (1995). The hindfoot alignment view. Foot & Ankle International, 16(9), 572-576. 2. Arena, C. B., Sripanich, Y., Leake, R., Saltzman, C. L., & Barg, A. (2021). Assessment of hindfoot alignment comparing weightbearing radiography to weightbearing computed tomography. Foot & Ankle International, 42(11), 1482-1490.

Category: Hindfoot; Other Introduction/Purpose: When the hindfoot is in varus the tarsal canal becomes visible on a lateral Xray (XR) and has been referred to as a 'target sign'. However, the sinus tarsi (ST) and tarsal canal (TC) are not easily visible radiographically when associated with a flatfoot. The dimensions of both the ST and TC in normal and flatfeet are unknown, but if understood, could help with the design and implantation of an arthroereisis, a commonly performed procedure for correction of pediatric flatfoot deformity. Knowing the size of the TC will also reduce postoperative complications of arthroereisis such as stiffness, resulting from too large an implant. The aim of this study was to take three-dimensional (3D) measurements of the TC in pediatric flatfeet under weightbearing (WB) conditions. Methods: This was a prospective IRB approved study in pediatric patients with flexible flatfeet and asymptomatic children without flatfeet who were reviewed and analyzed. Using 3D computer-aided design (CAD) models from weightbearing CT (WBCT) scans, the following parameters were measured: the widest diameter of the posteromedial tarsal canal (WDPTC), the narrowest supero- inferior diameter of the tarsal canal (NSDTC), the length of the tarsal sinus, (LTS), the length of the tarsal canal (LTC) and the tarsal sinus and canal volume (TSCV). Correlations between patient age, Meary's angle, foot and ankle offset (FAO), and each of the above measured parameters were investigated. Both weight bearing and non-weight bearing CT scans were used for study to investigate the effect of bearing weight on the above-mentioned parameters. (Figures 1, 2). Results: Twenty-two children with flexible flatfeet (age range 9-14) and fourteen children with no foot deformity (age 9-15) were included for study. With the WBCT the TSCV decreased by 20% in comparison with non-weightbearing evaluation. The TSCV, the widest diameter of the anterolateral tarsal sinus (WDATS) and LTC decreased in flatfeet both under WB and NWB conditions compared with the control group. A positive linear correlation was found between the TSCV and patient age (r = 0.7307, P < 0.0001), while negative linear correlations were found between the TSCV and FAO (r = -0.5188, P < 0.0001) and Meary's angle (r = -0.3132, P = 0.0019). The tarsal sinus and tarsal canal volume significantly decreased in the flatfoot group during weight bearing, while the volume of the tarsal canal remained unchanged. Older age was not associated with either a wider tarsal canal or its orientation. Conclusion: Although the tarsal sinus and canal volume was positively associated with patient age, there was a negative correlation with both the FAO and Meary's angle. These findings may be very relevant in future study of the subtalar joint in both children and adults, and clearly have an implication for treatment of the pediatric flatfoot with arthroereisis.

Category: Hindfoot; Ankle; Midfoot/Forefoot Introduction/Purpose: The foot and ankle offset (FAO) was developed as a 3D biometric tool to measure hindfoot alignment on weightbearing CT (WBCT) scans. It corresponds to the offset between the hindfoot-to-forefoot midline and the talus and is reported as a percentage of foot-length. (1) Recently, with increased availability of WBCT in both research and clinical practice, the FAO has been widely used for hindfoot alignment assessment. (2) However, after extensive review of WBCT scans the authors of this study have noticed that FAO has a high false negative rate. This study aimed to demonstrate why FAO is inadequate in assessing 3D hindfoot alignment using both case examples and mathematical algorithms. Methods: This was a retrospective study including a cohort of 31 cases with various clinical diagnoses selected from a data base of WBCT in 260 patients. The deformities included valgus or varus ankle deformities, hindfoot deformities combined with sagittal plane deformities of the foot and ankle, rocker bottom foot deformity, ankle equinus, metatarsus primus elevatus, and first metatarsal plantarflexion. All of the latter deformities caused one or more parts of the triangular base for FAO evaluation (the 1st metatarsal, the 5th metatarsal and the calcaneus) to remain off the floor. The medical charts and WBCT scans of each patient were reviewed to evaluate the deformities in more detail. The FAO was measured by two fellowship trained foot and ankle surgeons separately. The clinical and radiographic diagnoses were compared with the FAO value to determine the accuracy and utility of the latter measurement. Limitations of FAO as a semi 3D tool using the tripod theory in assessing the hindfoot alignment were also demonstrated mathematically. Results: For each of these 31 cases examined, the hindfoot alignment information reflected by the FAO value was vastly different from the clinical and imaging study findings. (Table 1). Using the reference value for FAO (Normal 2.3% ± 2.9%, Varus −11.6%± 6.9%, and Valgus 11.4% ± 5.7%), 24 out of 31 cases in the cohort had a normal FAO value, however, among them there were 7 with a valgus ankle or distal tibia plus a normal or cavovarus hindfoot, 2 varus ankles with a normal hindfoot, 1 varus ankle with a valgus hindfoot, 3 cavovarus feet, 1 clubfoot, 1 equinus ankle with cavovarus foot, 2 equinus ankle with severe valgus hindfoot, 4 severe valgus hindfoot and 1 varus hindfoot with sagittal plane deformities, 2 Muller Weiss Disease; 5 out of 31 cases had a varus FAO value, but they all had a valgus ankle with either a varus hindfoot or sagittal plane deformities; 2 out of 31 cases had a valgus FAO value, however both cases had a valgus ankle with a varus hindfoot. Thorough algorithm and geometric evidence were provided. Conclusion: FAO has a very limited capacity to reflect hindfoot deformities, understandable when analyzing how the FAO is designed and measured mathematically. It is not a 3D tool. It does not include the level of the ankle nor the tibia, therefore it is not appropriate nor capable to be used as a hindfoot alignment evaluation tool. The tripod and talus projection theories cannot reflect sagittal plane deformities or coronal plane rotation, and false results are inevitably generated. Reference: 1. Lintz F, Barton T, Millet M, Harries WJ, Hepple S, Winson IG. Ground reaction force calcaneal offset: a new measurement of hindfoot alignment. Foot Ankle Surg. 2012;18(1):9-14. 2. de Cesar Netto C, Day J, Godoy-Santos AL, Roney A, Barbachan Mansur NS, Lintz F, Ellis SJ, Demetracopoulos CA. The use of three-dimensional biometric Foot and Ankle Offset to predict additional realignment procedures in total ankle replacement. Foot Ankle Surg. 2022 Feb 16:S1268-7731(22)00036-4.

ABSTRACT Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses. There is an ongoing debate as to whether established infections by one Rickettsia species preclude the maintenance of the second species in ticks. Here, we identified two Rickettsia species in inoculum from Haemaphysalis montgomeryi ticks and subsequently obtained pure isolates of each species by plaque selection. The two isolates were classified as a transitional group and spotted fever group rickettsiae and named Rickettsia hoogstraalii str CS and Rickettsia rhipicephalii str EH, respectively. The coinfection of these two Rickettsia species was detected in 25.6% of individual field-collected H. montgomeryi. In cell culture infection models, R. hoogstraalii str CS overwhelmed R. rhipicephalii str EH with more obvious cytopathic effects, faster plaque formation, and increased cellular growth when cocultured, and R. hoogstraalii str CS seemed to polymerize actin tails differently from R. rhipicephalii str EH in vitro. This work provides a model to investigate the mechanisms of both Rickettsia-Rickettsia and Rickettsia-vector interactions. IMPORTANCE The rickettsiae are a group of obligate intracellular Gram-negative bacteria that include human pathogens causing an array of clinical symptoms and even death. There is an important question in the field, that is whether one infection can block the superinfection of other rickettsiae. This work demonstrated the coinfection of two Rickettsia species in individual ticks and further highlighted that testing the rickettsial competitive exclusion hypothesis will undoubtedly be a promising area as methods for bioengineering and pathogen biocontrol become amenable for rickettsiae.

Abstract Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P

Background: Chronic kidney disease (CKD) is a global public health issue. In recent years, the effectiveness of finerenone for treatment of CKD has been the subject of considerable debate. The main objective of the current meta-analysis was to validate the clinical efficacy and safety of finerenone in patients with CKD.Methods: Seven databases were searched for randomized controlled trials (RCTs) comparing finerenone with placebo in patients with CKD. Data from eligible studies were extracted, and the Cochrane risk of bias tool utilized for evaluating the methodological quality of RCTs. The effect size was estimated using the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI).Results: Five trials (n = 13,078) were included. Compared to placebo groups, the urinary albumin-to-creatinine ratio (UACR) mean from the baseline was significantly lower [MD −0.30 (95% CI −0.32, −0.28), p < 0.00001], while a decrease in the estimated glomerular filtration rate (eGFR) from baseline was significantly higher [MD −2.44 (95% CI −2.82, −2.05), p < 0.00001] for the finerenone groups. Furthermore, the proportion of patients with decreased eGFR (≥40%) post-baseline was significantly lower [RR 0.85 (95% CI 0.78, 0.93), p = 0.0002], along with end-stage kidney disease (ESKD) [RR 0.80 (95% CI 0.65, 0.99), p = 0.04] and cardiovascular events (CVs) [RR 0.88 (95% CI 0.80, 0.95), p < 0.003] in the finerenone groups. In terms of safety, the increase in the serum potassium concentration and incidence of hyperkalemia was significantly higher for the finerenone groups [MD 0.17 (95% CI 0.10, 0.24), p < 0.00001; RR 2.03 (95% CI 1.83, 2.26), p < 0.00001, respectively], but the incidence of adverse events (AEs) was similar to placebo [RR 1.00 (95% CI 0.98–1.01), p = 0.67]. In all cases, the results were rated as providing moderate-quality or high-quality evidence.Conclusion: Data from our meta-analysis suggest that finerenone confers significant renal and cardiovascular benefits in patients with CKD. While higher risk of hyperkalemia was observed with finerenone than placebo, differences in AEs were not significant. Finerenone may therefore present a novel promising therapeutic agent for patients with CKD.Systematic Review Registration: [https://inplasy.com/inplasy-2021-9-0020/], identifier [INPLASY202190020].

The long-lasting co-evolution of ticks with pathogens results in mutual adaptation. Blood-feeding is one of the critical physiological behaviors that have been associated with the tick microbiome; however, most knowledge was gained through the study of laboratory-reared ticks. Here we detached Ixodes persulcatus ticks at different stages of blood-feeding from human patients and performed high-throughput transcriptomic analysis on them to identify their virome and genes differentially expressed between flat and fully fed ticks. We also traced bloodmeal sources of those ticks and identified bats and three other potential mammalian hosts, highlighting the public health significance. We found Jingmen tick virus and 13 putative new viruses belonging to 11 viral families, three of which even exhibited high genetic divergence from viruses previously reported in the same tick species from the same geographic region. Furthermore, differential expression analysis suggested a downregulation of antioxidant genes in the fully fed I. persulcatus ticks, which might be related to bloodmeal-related redox homeostasis. Our work highlights the significance of active surveillance of tick viromes and suggests a role of reactive oxygen species (ROS) in modulating changes in the microbiome during blood-feeding.

Broussonetia papyrifera L. (paper mulberry) is an alternative woody plant, which can used to replace part of the protein feed for ruminants. Ensiling is an effective way to preserve fresh pasture and to solve the problem of stable storage and feed conversion of paper mulberry in the rapid growth period. However, low dry matter (DM), water-soluble carbohydrate, and lactic acid bacteria (LAB) reduce the quality of paper mulberry silage. This study assesses the influence of wilting time (0 h and 3.5 h; lighting: 3.43 × 104 Lux) and three additives (Enterococcus durans, CL; cellulase, CE; and formic acid, FA) on the fermentation quality, aerobic stability, and bacterial community of whole plant B. papyrifera silage. The whole plant B. papyrifera sample was mowed and wilted for 0 h and 3.5 h, and then had CL, CE, or FA added, followed by 60 days of ensiling. The results show all silage samples had high fermentation quality with pH below 4.2, ammonia-nitrogen below 100 g/kg DM, and no detectable butyric acid. The additives protected the DM and the crude protein from protease activity (p < 0.05), and CL was the most effective among them. Furthermore, wilting time influenced the silage’s bacterial communities, but overall, CL treatment had the greatest impact on bacterial communities. Wilting time and formic acid treatment significantly improved aerobic stability (p < 0.05). Enterococcus was positively correlated with lactic acid (LA), while negatively correlated with LA and Weissella (p < 0.001). Enterococcus was identified as the main driver of the whole plant paper mulberry ensiling process in the present study. In conclusion, compared to other additives, LAB is the most effective and economical to improve the fermentation quality and reduce the protein degradation of whole plant paper mulberry silage. Our findings provide a theoretical basis to improve the quality and production of paper mulberry silage.

Semiliquidambar cathayensis is a special and endangered plant in China, used for traditional Chinese medicine and in landscape applications. Predicting the impact of climate change on the distribution of S. cathayensis is crucial for its protection and the sustainable use of resources. We used the maximum entropy (MaxEnt) model optimized by the ENMeval data packet to analyze the potential geographic distribution changes of S. cathayensis in 12 provinces of Southern China for the different periods since the last interglacial period (LIG, 120–140 ka). Considering the potential geographic distribution changes in the province, and based on the two climate scenarios of Representative Concentration Pathways (RCP) 2.6 and RCP 8.5, the distribution range of S. cathayensis was analyzed and we predicted the range for the 2050s (average for 2041–2060) and 2070s (average for 2061–2080). The area under AUC (Area under the receiver operating characteristic (ROC) curve) is 0.9388 under these parameters, which indicates that the model is very accurate. We speculate that the glacial period refugia were the Nanling and Wuyi Mountains for S. cathayensis, and central and Western Fujian and Taiwan are likely to be the future climate refugia. In the mid-Holocene (MH, 6 ka), the growth habitat was 32.41% larger than the modern habitat; in the 2050s and 2070s (except RCP2.6–2070s), the growth habitat will shrink to varying degrees, so efforts to support its in situ and ex situ conservation are urgently needed. The jackknife test showed that the main factors affecting the geographical distribution of S. cathayensis were annual precipitation, precipitation of the wettest month, and precipitation of the driest month. The annual precipitation may be the key factor restricting the northward distribution of S. cathayensis. In general, the centroid of the distribution of S. cathayensis will move northward. The centroid of the adaptive habitats will move northward with the highest degree of climate abnormality. We think that Hainan Island is the most likely origin of S. cathayensis. These findings provide a theoretical basis for the establishment of genetic resources protection measures, the construction of core germplasm resources, and the study of the formation and evolution of Hamamelidaceae.

Category: Trauma Introduction/Purpose: The first tarsometatarsal (TMT) joint is very crucial for midfoot stability. To address its importance, retrospective analyses of treatment for the first TMT joint dislocation with Lisfranc injury was performed in a multi-center manner. Comparison of open reduction internal fixation (ORIF) and primary arthrodesis was conducted for the injury. Methods: This multi-center study was involved ten clinical institutions in different area of China. .From January 2003 to June 2015, 126 Lisfranc injuries with first TMT joint dislocation underwent surgical intervention. Of this group, forty one (32.5%) feet were first TMT joint dislocation only. Eighty five feet were first TMT joint dislocation and fractures. They were 76 males (60.3%) and 50 females (39.7%) with a mean age of 45.5 (range, 20-87) years. The duration from injury to surgery is 11.7 (range, 4-26) days. Two groups were divided by surgery methods as open reduction internal fixation (ORIF) group and primary arthrodesis group. Ninety two patients were performed by ORIF, while primary arthrodesis group including 34 cases. Outcome measures included clinical examination, radiographs, AOFAS ankle-hindfoot scores, visual analogue scale (VAS) and SF-36 scores. Complications and revision rate were analyzed as well. Results: 126 patients were followed up for 29.5 months. At 1.5 years postoperatively, the AOFAS score was 79 and 85 in ORIF group and arthrodesis group.The VAS score was 3.1 separately in two groups.The mean Physical Functioning sores of SF-36 was 80.3 points and 83.5• points. The Bodily Pain score of SF-36 was 76.1 points and 84.6• points.Redislocation of first tarsometarsal joint were observed in 16 cases among ORIF group.36 patients in ORIF group had pain in midfoot, eight of them had persistent pain with the development of deformity or osteoarthrosis.No redislocation and no hardware failure was identified in arthrodesis group Conclusion: Primary stable arthrodesis of the first ray gives a better short and medium term outcome than open reduction and internal fixation for Lisfranc injury with the first ray dislocation. Possible complication and revision could be avoided by primary arthrodesis for dislocated first ray injuries.

Category: Midfoot/Forefoot Introduction/Purpose: Müller-Weiss disease is an uncommon osteonecrosis of the tarsal navicular of unknown etiology. Most of them could be treated by non-surgical methods. But some severe deformity and fail to conserved methods. In those cases, surgery may be a reasonable approach. Methods: From January 2005 to Septermber 2016, we treated 69 patients suffering from Müller-Weiss disease, using the surgical arthrodesis of the talonavicular joint and naviculocuneiform joint with tricortical autologous iliac crest block fixed by screws and plate. Results: All Maceira grades were included. We reviewed the medical records of the patients and took the radiological preoperative and postoperative evaluation. The preoperative and postoperative clinical functions were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot Scale. To treat Müller-Weiss disease, we introduced a surgical arthrodesis of the talonavicular joint and naviculocuneiform joint with tricortical autologous iliac crest bone block fixed by screws and plate. The median follow up was 26 months. All the feet fused solidly. The median time for complete fusion was 13 weeks. The median AOFAS ankle-hindfoot score improved from 45 points preoperatively to 86 points at last follow-up. Conclusion: The results of this series demonstrate the arthrodesis of the TNJ and NCJ with tricortical autologous iliac crest graft is a reasonable way for treatment of Müller -Weiss disease. Based on our experience with the patients, we believe that emphasis of the restoration of the length and alignment of the medial column could achieve a good outcome.

Category: Trauma Introduction/Purpose: It is controversial for operative repair of deltoid ligament in acute ankle fractures. To investigate the indication for surgical interference and the clinical outcome about repair whole deltoid ligament rupture associating with ankle fractures. Methods: We performed multiple-center study in 4 clinical centers in 4 cities of China. From January 2006 to December 2011, of 1533 ankle fractures operated, 131 deltoid ligament rupture were identified and repaired operatively. They were 74 males and 57 females with a mean age of 37.2 years (range, 15-83 years). Clinical examination, radiographs, AOFAS ankle-hindfoot scores and visual analogue scale were used for outcome measurement. Results: All incision healed primarily. 106 patients were followed up for 12 to 72 months with the mean follow-up of 27 months. The mean time of fracture union was 14.5 weeks (range, 9-16 weeks). The mean AOFAS ankle-hindfoot score at last follow-up was 91.4 points (range, 83-100 points). The mean score of VAS was 1.2 points (range, 0-6 points). The mean score of SF-36 was 91.2 points (range, 80-96 points). There was no ankle instability and post-trauma osteoarthritis. Conclusion: This multiple-center study demonstrated that deltoid ligament repair can benefit patients with unstable ankle after fracture fixation. A reasonable clinical evaluation and surgical repair could be done, choosing an appropriate repair technique according to the site of deltoid ligament rupture.

Category: Lesser Toes Introduction/Purpose: The purpose of this study was to evaluate the clinical outcomes using a double stemmed flexible silicone prosthesis for the treatment of Freiberg disease in its late stages. Methods: The subjects consisted of 13 feet from 13 cases suffering from Freiberg disease in their late stages. They underwent double stemmed flexible silicone prosthesis replacement for metatarsophalangeal joints. The average age was 63.8 (range 30~88) years. The average follow up period was 26 (range 18–42) months. The investigation was carried out using the range of motion (ROM), visual analog scale (VAS), AOFAS and Maryland metatarsophalangeal joints scale before surgery and at the latest follow-up. Results: The average ROM of dorsal flexion improved from 39.3±6.1° before surgery to 75.4±8.6° at latest follow-up (p

Category: Midfoot/Forefoot Introduction/Purpose: To characterize clinical treatment of the malunion after midfoot injury. Methods: 22 cases of malunion following complex midfoot injury from 2004 to 2012. They were 19 men and 3 women with mean age of 37.8. The foot deformity was categorized into 3 types and 3 subtypes, with type? indicating normal foot arch (type ?a forefoot abduction, ?b forefoot adduction and Ic forefoot normal), type? Cavus deformity (subtype is same as?), and type ? flatfoot deformity (subtype is same as?) . There were 2 cases of type?a, 4 cases of type?c, 9 cases of type?a, 4 cases of type ?a, 3 cases of type ?c in our cohort. According to the malunion typing, osteotomy, joint arthrodesis, or realignment was used to correct deformity. Clinical outcomes were evaluated by AOFAS score and VAS. Results: All the patients were followed up for average 34.7 months.The mean VAS score was 2.0 points (0-6) and mean AOFAS score was 83.9±2.3 points (73-94) at the last follow-up, giving an excellent to good rate of 81.8%. All cases obtained favorable functional outcomes without bone nonunion, except one patient who still suffered from midfoot walking discomfort 3 years after operation. Conclusion: Operative management of malunion following midfoot injury is effective and good results can only be obtained by stabilizing injured joint, realignment and recover foot arch.Our typing of the midfoot malunion is helpful in the operative treatment.

Category: Ankle Introduction/Purpose: The purpose of current study was to retrospectively analyze the clinical outcomes of buttress plate treatment of posterior pilon fractures. Methods: Between January 2005 and December 2016, 58 patients with posterior pilon fractures underwent buttress plate fixation. There were 32 males and 26 females and the mean age was 40.2years (range, 23 to 73 years). Preoperative radiographs, CT scans and three dimensional reconstructions were used to evaluate the fracture patterns. On the basis of the extension of the fracture lines presented on the CT scans, a posterolateral approach or a combination of both posterolateral and posteromedial approaches were used to reduce and fixate the posterior malleolar fragments. Clinical and radiographic examinations were used for postoperative follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the Visual Analogue Scale (VAS) were used to evaluate the functional outcomes. Results: According to the CT scan images, the posterior pilon fractures were classified into 3 types. 51 patients were available for follow-up. The mean time of follow-up was 44.8 months. The mean AOFAS score was 84.3 points, and the mean VAS score was 1.6 points. One patient was found with ankle joint swelling and long term walking discomfort at 2-year follow-up. Other patients received favorable functional outcomes. No hardware failure occurred. Conclusion: The clinical outcomes of buttress plate treatment of posterior pilon fractures were satisfactory. Buttress plating availed the patients to return to earlier weight-bearing and functional exercises.

PHRF1 functions as an essential component of the TGF-β tumor suppressor pathway by triggering degradation of the homeodomain repressor factor TGIF. This leads to redistribution of cPML into the cytoplasm, where it coordinates phosphorylation and activation of Smad2 by the TGF-β receptor. In acute promyelocytic leukemia (APL), acquisition of PML-RARα is known to impede critical aspects of TGF-β signaling, including myeloid differentiation. Although these defects are thought to rely on suppression of cPML activity, the mechanisms underlying this phenomenon remain enigmatic. Here, we find that an abnormal function of PML-RARα is to interfere with TGIF breakdown, presumably by competing with PHRF1 for binding to TGIF, culminating in cPML sequestration and inactivation. Enforcing PHRF1 activity is sufficient to restore TGF-β cytostatic signaling in human blasts and suppress APL formation in a mouse model of APL, providing proof-of-concept data that suppression of PHRF1 activity by PML-RARα represents a critical determinant in APL pathogenesis.

The homeodomain protein TGIF (TG-interacting factor) restricts TGF-β/Smad cytostatic signaling by interfering with the nucleocytoplasmic transit of the tumor suppressor cPML. Here, we identify PHRF1 as a ubiquitin ligase that enforces TGIF decay by driving its ubiquitination at lysine 130. In so doing, PHRF1 ensures redistribution of cPML into the cytoplasm, where it associates with SARA and coordinates activation of Smad2 by the TGF-β receptor. The PHRF1 gene resides within the tumor suppressor locus 11p15.5, which displays frequent loss in a wide variety of malignancies, including breast cancer. Remarkably, we found that the PHRF1 gene is deleted or silenced in a high proportion of human breast cancer samples and cancer cell lines. Reconstitution of PHRF1 into deficient cells impeded their propensity to form tumors in vivo, most likely because of the reemergence of TGF-β responsiveness. These findings unveil a paradigm behind inactivation of the cPML tumor suppressor network in human malignancies.

The molecule of the title compound, C15H14N2O2 is almost planar, the dihedral angle between the 6-methyl-1H-benzimidazole plane and the 2-methoxyphenol plane being 6.9 (2)°. An intramolecular O—H...N hydrogen bond is present. Adjacent molecules are linked by N—H...O hydrogen bonds into a three-dimensional network structure. The benzoimidazole methyl group and its attached C atom are positionally disordered in a 0.724 (4):0.276 (4) ratio.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications. [ABSTRACT FROM AUTHOR]