A deep catalogue of protein-coding variation in 983,578 individuals.

Rare coding variants that significantly impact function provide insights into the biology of a gene1-3. However, ascertaining their frequency requires large sample sizes4-8. Here, we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. 23% of the Regeneron Genetics Center Million Exome data (RGC-ME) comes from non-European individuals of African, East Asian, Indigenous American, Middle Eastern, and South Asian ancestry. This catalogue includes over 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss-of-function, we identify 3,988 loss-of-function intolerant genes, including 86 that were previously assessed as tolerant and 1,153 lacking established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions depleted of missense variants despite being tolerant to pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this important resource of coding variation from the RGC-ME accessible via a public variant allele frequency browser.

Genotyping, sequencing and analysis of 140,000 adults from Mexico City.

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Exome sequencing and analysis of 454,787 UK Biobank participants.

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10-11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.

Exome sequencing and characterization of 49,960 individuals in the UK Biobank.

The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.

Defect-induced discrete breather in dissipative optical lattices with weak nonlinearity.

It is widely believed that the discrete breather (DB) can only be created when the nonlinearity is strong in nonlinear systems. However, we here establish that this belief is incorrect. In this work, we systemically investigate the generation of DBs induced by coupling of the defects and nonlinearity for Bose-Einstein condensates in dissipative optical lattices. The results show that, only in a clean lattice is strong nonlinearity a necessary condition for generating of DB; whereas, if the lattice has a defect, the DBs can also be discovered even in weak nonlinearity, and its generation turns out to be controllable. In addition, we further reveal a critical interval of the defect in weak nonlinearity, within which DBs can be found, while outside DBs do not exist. Furthermore, we also explore the impact of multiple defects on the generation of DBs, and analyze the underlying physical mechanisms of these interesting phenomena. The results not only have the potential to be used for more precise engineering in the DB experiments, but also suggest that the DB may be ubiquitous since the defects and dissipation are unavoidable in real physics.

Comparison of freehand technique and a novel laser-guiding navigation system in femoral neck-cannulated screw fixation: a randomized controlled trial.

Cannulated screw fixation is essential in treating femoral neck fractures, and the widely used freehand technique has several limitations. Therefore, we designed a new laser-positioning and navigation system and compared its efficacy with that of the traditional freehand technique in the cannulated screw fixation of femoral neck fractures. This randomized controlled single-blind trial recruited patients with femoral neck fracture, who were treated using either the newly designed laser-navigation device or the freehand technique. In in-vitro experiments, using the femoral neck model, the laser group was better than the freehand group in terms of operation time (P = 0.0153) and radiation exposure time (P < 0.001). In in-vivo experiments, involving 30 patients (15 in each group), the laser group was better than the freehand group in terms of operation time (P < 0.001), radiation exposure time (P < 0.001), blood loss (P < 0.001) and first success rate (P = 0.03). There was no difference in visual analog scale score, Harris score, and fracture-healing time between the two groups. In conclusion, the novel laser-guiding navigation system resulted in shorter operation time, less radiation exposure, and higher first success rate compared with the freehand technique. Further qualified investigations with a larger number of patients and longer follow-up are required in the future.

Genetic Variation, DIMBOA Accumulation, and Candidate Gene Identification in Maize Multiple Insect-Resistance.

Maize seedlings contain high amounts of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and the effect of DIMBOA is directly associated with multiple insect-resistance against insect pests such as Asian corn borer and corn leaf aphids. Although numerous genetic loci for multiple insect-resistant traits have been identified, little is known about genetic controls regarding DIMBOA content. In this study, the best linear unbiased prediction (BLUP) values of DIMBOA content in two ecological environments across 310 maize inbred lines were calculated; and their phenotypic data and BLUP values were used for marker-trait association analysis. We identified nine SSRs that were significantly associated with DIMBOA content, which explained 4.30-20.04% of the phenotypic variation. Combined with 47 original genetic loci from previous studies, we detected 19 hot loci and approximately 11 hot loci (in Bin 1.04, Bin 2.00-2.01, Bin 2.03-2.04, Bin 4.00-4.03, Bin 5.03, Bin 5.05-5.07, Bin 8.01-8.03, Bin 8.04-8.05, Bin 8.06, Bin 9.01, and Bin 10.04 regions) supported pleiotropy for their association with two or more insect-resistant traits. Within the 19 hot loci, we identified 49 candidate genes, including 12 controlling DIMBOA biosynthesis, 6 involved in sugar metabolism/homeostasis, 2 regulating peroxidases activity, 21 associated with growth and development [(auxin-upregulated RNAs (SAUR) family member and v-myb avian myeloblastosis viral oncogene homolog (MYB)], and 7 involved in several key enzyme activities (lipoxygenase, cysteine protease, restriction endonuclease, and ubiquitin-conjugating enzyme). The synergy and antagonism interactions among these genes formed the complex defense mechanisms induced by multiple insect pests. Moreover, sufficient genetic variation was reported for DIMBOA performance and SSR markers in the 310 tested maize inbred lines, and 3 highly (DIMBOA content was 402.74-528.88 µg g-1 FW) and 15 moderate (DIMBOA content was 312.92-426.56 µg g-1 FW) insect-resistant genotypes were major enriched in the Reid group. These insect-resistant inbred lines can be used as parents in maize breeding programs to develop new varieties.

Integrated QTL Mapping, Meta-Analysis, and RNA-Sequencing Reveal Candidate Genes for Maize Deep-Sowing Tolerance.

Synergetic elongation of mesocotyl and coleoptile are crucial in governing maize seedlings emergence, especially for the maize sown in deep soil. Studying the genomic regions controlling maize deep-sowing tolerance would aid the development of new varieties that are resistant to harsh conditions, such as drought and low temperature during seed germination. Using 346 F2:3 maize population families from W64A × K12 cross at three sowing depths, we identified 33 quantitative trait loci (QTLs) for the emergence rate, mesocotyl, coleoptile, and seedling lengths via composite interval mapping (CIM). These loci explained 2.89% to 14.17% of phenotypic variation in a single environment, while 12 of 13 major QTLs were identified at two or more sowing environments. Among those, four major QTLs in Bin 1.09, Bin 4.08, Bin 6.01, and Bin 7.02 supported pleiotropy for multiple deep-sowing tolerant traits. Meta-analysis identified 17 meta-QTLs (MQTLs) based on 130 original QTLs from present and previous studies. RNA-Sequencing of mesocotyl and coleoptile in both parents (W64A and K12) at 3 cm and 20 cm sowing environments identified 50 candidate genes expressed differentially in all major QTLs and MQTLs regions: six involved in the circadian clock, 27 associated with phytohormones biosynthesis and signal transduction, seven controlled lignin biosynthesis, five regulated cell wall organization formation and stabilization, three were responsible for sucrose and starch metabolism, and two in the antioxidant enzyme system. These genes with highly interconnected networks may form a complex molecular mechanism of maize deep-sowing tolerance. Findings of this study will facilitate the construction of molecular modules for deep-sowing tolerance in maize. The major QTLs and MQTLs identified could be used in marker-assisted breeding to develop elite maize varieties.

Exogenous Serotonin (5-HT) Promotes Mesocotyl and Coleoptile Elongation in Maize Seedlings under Deep-Seeding Stress through Enhancing Auxin Accumulation and Inhibiting Lignin Formation.

Serotonin (5-HT), an indoleamine compound, has been known to mediate many physiological responses of plants under environmental stress. The deep-seeding (≥20 cm) of maize seeds is an important cultivation strategy to ensure seedling emergence and survival under drought stress. However, the role of 5-HT in maize deep-seeding tolerance remains unexplored. Understanding the mechanisms and evaluating the optimal concentration of 5-HT in alleviating deep-seeding stress could benefit maize production. In this study, two maize inbred lines were treated with or without 5-HT at both sowing depths of 20 cm and 3 cm, respectively. The effects of different concentrations of 5-HT on the growth phenotypes, physiological metabolism, and gene expression of two maize inbred lines were examined at the sowing depths of 20 cm and 3 cm. Compared to the normal seedling depth of 3 cm, the elongation of the mesocotyl (average elongation 3.70 cm) and coleoptile (average elongation 0.58 cm), secretion of indole-3-acetic acid (IAA; average increased 3.73 and 0.63 ng g-1 FW), and hydrogen peroxide (H2O2; average increased 1.95 and 0.63 µM g-1 FW) in the mesocotyl and coleoptile were increased under 20 cm stress, with a concomitant decrease in lignin synthesis (average decreased 0.48 and 0.53 A280 g-1). Under 20 cm deep-seeding stress, the addition of 5-HT activated the expression of multiple genes of IAA biosynthesis and signal transduction, including Zm00001d049601, Zm00001d039346, Zm00001d026530, and Zm00001d049659, and it also stimulated IAA production in both the mesocotyl and coleoptile of maize seedlings. On the contrary, 5-HT suppressed the expression of genes for lignin biosynthesis (Zm00001d016471, Zm00001d005998, Zm00001d032152, and Zm00001d053554) and retarded the accumulation of H2O2 and lignin, resulting in the elongation of the mesocotyl and coleoptile of maize seedlings. A comprehensive evaluation analysis showed that the optimum concentration of 5-HT in relieving deep-seeding stress was 2.5 mg/L for both inbred lines, and 5-HT therefore could improve the seedling emergence rate and alleviate deep-seeding stress in maize seedlings. These findings could provide a novel strategy for improving maize deep-seeding tolerance, thus enhancing yield potential under drought and water stress.

The changing trends of the knee function after anterior and posterior cruciate ligaments reconstruction with all-inside arthroscopy technique.

We aimed to summarize the effectiveness and changing trends of reconstruction for the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injuries using all-inside arthroscope technique. Between May 2013 and May 2019, 29 patients with ACL and PCL ligaments rupture were included. All the patients were male, with a mean age of 25.2±2.9 years. The mean follow-up period was 2.4±0.7 years (Range, 2-4 years). Reconstruction surgery of the ACL and PCL ligaments was performed by using autologous hamstring tendon with all-inside arthroscopy technique. The anterior and posterior drawer test, Lachman test, Pivot-shift test, stress test, IKDC score, Lysholm score, Tenger score were analyzed clinically. At the last follow-up, the symptoms were improved significantly, the anterior drawer test was normal and 1 degree in 96.6%, posterior drawer test in 89.7%, pivot shift test in 96.6%, Lachman test in 93.1%, and stress test in 93.3%, the stability was improved significant(P<0.05). The IKDC-2000 standard score was normal and near normal in 96.6%. The IKDC subjective score, Lysholm score, and Tenger scores results at the last follow-up were significantly improved when compared with those before operation ( P<0.05). The changing trends of function evaluation score in the first six months were most obviously better, especially in the third month. All-inside arthroscopy technique is an effective procedure for the ACL and PCL ligaments injuries, and the first six months (especially the third month) after the reconstruction is the key period for a successful recovery. However, there was still a significant improvement at the later stage of rehabilitation.

Sparse Project VCF: efficient encoding of population genotype matrices.

SUMMARY: Variant Call Format (VCF), the prevailing representation for germline genotypes in population sequencing, suffers rapid size growth as larger cohorts are sequenced and more rare variants are discovered. We present Sparse Project VCF (spVCF), an evolution of VCF with judicious entropy reduction and run-length encoding, delivering >10× size reduction for modern studies with practically minimal information loss. spVCF interoperates with VCF efficiently, including tabix-based random access. We demonstrate its effectiveness with the DiscovEHR and UK Biobank whole-exome sequencing cohorts. AVAILABILITY AND IMPLEMENTATION: Apache-licensed reference implementation: github.com/mlin/spVCF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of open reduction and fixation with hook plate and modified closed reduction and fixation with tightrope loop plate for treatment of rockwood type III acromioclavicular joint dislocation.

OBJECTIVE: To compare the outcomes of open reduction and hook plate fixation (ORHPF) and modified TightRope loop plate fixation (MTRLPF) in the treatment of Rockwood type III acromioclavicular joint dislocation. METHODS: This was a retrospective study. Data on 71 patients with Rockwood type III acromioclavicular joint dislocation who underwent either ORHPF (n = 39) or MTRLPF (n = 32) between January 2016 and October 2019 were extracted and analyzed. Baseline data at injury were compared to evaluate the balance. The disabilities of the arm, shoulder, and hand (DASH) score, Constant-Murley score and visual analog scores (VAS) score at 1 month, 3 months, 6 months and 12 months after operation were compared; further, at 12 months coracoclavicular distance and related complications were evaluated and compared. RESULTS: Both groups did not differ for any baseline data. At 1 and 3 months after operation, MTRLPF group exhibited a significantly better performance than the ORHPF group in VAS (1 month: 2.4 ± 1.8 vs 3.0 ± 1.7; 3 months: 1.2 ± 1.4 vs 1.8 ± 1.6), Constant-Murley (1 month: 75.2 ± 11.2 vs 63.8 ± 13.7; 3 months: 81.4 ± 9.8 vs 75.8 ± 10.6), DASH (1 month: 33.6 ± 6.8 vs 40.6 ± 6.1; 3 months: 21.2 ± 7.4 vs 25.6 ± 6.6). At 6 months, only Constant-Murley remained marginally significant (p = 0.048). At 12 months, no statistical difference was observed for any outcome variable (all P > 0.05 for VAS, Constant-Murley and DASH), coracoclavicular distance (12.7 ± 1.6 mm vs 12.2 ± 1.6 mm; P = 0.374), or overall complication rate (P = 0.763). CONCLUSIONS: For Rockwood type III acromioclavicular joint dislocation, both methods can achieve satisfactory 1-year results, but modified minimally invasive TightRope treatment is more advantageous in early functional recovery at 1 and 3-month follow-ups.

Comparison of freehand technique and a novel laser guiding navigation in distal locking of femoral intramedullary nails: a randomized controlled trial.

BACKGROUND: Intramedullary nail (IMN) is one of the key essential minimally invasive "weapons" in orthopaedic trauma, while the distal locking is still challenging for surgeons. Although there are various inventions and technologies to improve the locking procedure, there are still problems such as inaccurate positioning, excessive radiation exposure, low first success rate and long learning curve. Therefore, a new laser guiding navigation device was designed and compared with the traditional freehand (FH) technique in the distal locking of femoral IMN. METHODS: This randomized controlled single-blind trial recruited patients with femoral diaphyseal fracture. The self-designed laser navigation device (laser group) and freehand technique (FH group) were used in the distal locking of the IMNs. The patients enrolled were randomized into FH group and laser group, all operations were performed by two surgeons of the same level. The differences between the two groups were compared in terms of radiation exposure time, operative time, first success rate, blood loss, visual analogue score (VAS), Harris score and healing time. RESULTS: 32 patients ended the study period and 16 patients in each group. The results showed that the laser group was better than the FH group in terms of distal locking time (10(9/11) vs 19.5 (17.25/21) min, Z = 4.83, P < 0.001), distal locking radiation exposure time (46.5 (41.25/51.75) vs 105 (88.25/140) s, Z = 4.807, P < 0.001), first success rate (30/32 vs 20/32, χ2 = 9.143, P = 0.002) and blood loss (60 (50-100) vs 150 (105-192.5) mL, Z = 3.610, P = 0.0003). There was no difference in Harris score, VAS score, or fracture healing time between the two groups. CONCLUSION: Compared with the FH technique, the novel laser guiding navigation device for distal locking of femoral IMN has the advantages of shorter operative time, less radiation exposure and higher first success rate. Trial registration Chinese Clinical Trial Registry, ChiCTR2200060236. Registered 23 May 2022, https://www.chictr.org.cn/showprojen.aspx?proj=169130.

Combined application of moist exposed burn ointment and maggot therapy in wound healing.

OBJECTIVE: Hard-to-heal wounds are a global health challenge, and effective treatments are still lacking. Moist exposed burn ointment (MEBO) and maggots are traditional treatments for promoting wound healing. This study was a preliminary exploration of combined maggot therapy and MEBO in the treatment of hard-to-heal wounds. METHOD: A coexistence experiment was conducted to determine the survival rates of maggots in MEBO. The maggots were placed in two different existence conditions: one set in MEBO (MEBO group), and another set as the control group (no MEBO) to compare survival rates. Case reports describe the use of the combined application of MEBO and maggots in the treatment of patients with hard-to-heal wounds. RESULTS: The coexistence experiment indicated that maggots in the MEBO group had a higher survival rate. From the therapeutic effect of the clinical cases (n=7), the combined application was safe and effective, with all the reported wounds eventually healing. CONCLUSION: Based on the findings of this study, we believe the combined application of MEBO and maggots is a promising way of promoting wound healing. Further studies and clinical trials are needed to elucidate the mechanism of the combined application in promoting wound healing and to more persuasively clarify the therapeutic effect.

Obesity regulates miR-467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC-derived exosome LncRNA H19.

This study explored the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes on the treatment of obesity-induced fracture healing. Quantitative real-time PCR was used to detect the expression of lncRNA H19, miR-467 and Hoxa10 and combined with WB detection to detect osteogenic markers (RUNX2, OPN, OCN). Determine whether exosomes have entered BMSCs by immunofluorescence staining. Alkaline phosphatase (ALP) and alizarin red staining (ARS) staining were used to detect ALP activity and calcium deposition. We found that high-fat treatment can inhibit the secretion of BMSCs-derived exosomes and affect the expression of H19 carried by them. In vivo and in vitro experiments show that high-fat or obesity factors can inhibit the expression of osteogenic markers and reduce the staining activity of ALP and ARS. The treatment of exosomes from normal sources can reverse the phenomenon of osteogenic differentiation and abnormal fracture healing. Further bioinformatics analysis found that miR-467 as a regulatory molecule of lncRNA H19 and Hoxa10, and we verified the targeting relationship of the three through dual luciferase report experiments. Further, we found similar phenomena in ALP and ARS staining. Bone marrow mesenchymal stem cell-derived exosomes improve fracture healing caused by obesity.

Profiling and Leveraging Relatedness in a Precision Medicine Cohort of 92,455 Exomes.

Large-scale human genetics studies are ascertaining increasing proportions of populations as they continue growing in both number and scale. As a result, the amount of cryptic relatedness within these study cohorts is growing rapidly and has significant implications on downstream analyses. We demonstrate this growth empirically among the first 92,455 exomes from the DiscovEHR cohort and, via a custom simulation framework we developed called SimProgeny, show that these measures are in line with expectations given the underlying population and ascertainment approach. For example, within DiscovEHR we identified ∼66,000 close (first- and second-degree) relationships, involving 55.6% of study participants. Our simulation results project that >70% of the cohort will be involved in these close relationships, given that DiscovEHR scales to 250,000 recruited individuals. We reconstructed 12,574 pedigrees by using these relationships (including 2,192 nuclear families) and leveraged them for multiple applications. The pedigrees substantially improved the phasing accuracy of 20,947 rare, deleterious compound heterozygous mutations. Reconstructed nuclear families were critical for identifying 3,415 de novo mutations in ∼1,783 genes. Finally, we demonstrate the segregation of known and suspected disease-causing mutations, including a tandem duplication that occurs in LDLR and causes familial hypercholesterolemia, through reconstructed pedigrees. In summary, this work highlights the prevalence of cryptic relatedness expected among large healthcare population-genomic studies and demonstrates several analyses that are uniquely enabled by large amounts of cryptic relatedness.

Dispersive and filter loss performance of calcium carbonate nanoparticles in water for drilling fluid applications.

Adding nanoparticles in a drilling fluid can aid in the sealing of the nanopores in the borehole wall rock and the mud cake; in this way, the filtrate loss of the drilling fluid can be reduced and the borehole wall is stabilized. In this work, the spectrophotometric method was used to study the effect of dispersants on calcium carbonate nanoparticles. The best dispersion effect was achieved at cetyltrimethyl ammonium bromide (CTAB) concentration of 4 wt%, dispersing time of 45 min, pH value of 8 and stirring speed of 900 rpm. The structure analysis showed that the adsorption layer was formed on the surface of calcium carbonate nanoparticles after CTAB modification, and no new crystalline compounds appeared. Under these optimized dispersing conditions, aggregation was prevented as manifested by the dramatically decreased average particle size of calcium carbonate nanoparticles while the surface hydrophilicity and Zeta potential of calcium carbonate nanoparticles both increased. Furthermore, we showed that a drilling fluid incorporating such well dispersed calcium carbonate nanoparticles exhibit decreased filter loss and thus better performance in sealing compared to the calcium carbonate nanoparticles without dispersants.

Clinical and functional comparison of dynamic hip screws and intramedullary nails for treating proximal femur metastases in older individuals.

OBJECTIVE: To compare the outcomes of dynamic hip screws (DHS) and intramedullary nailing (IMN) in the treatment of extra-capsular metastatic carcinoma of the proximal femur. METHODS: A retrospective case analysis method was used to examine data of patients with proximal metastatic cancer of the femur who were treated with internal fixation in Department of Orthopaedics, Beijing Friendship Hospital, from January 2007 to December 2018. Blood loss, postoperative pain, functional score, length of stay, and survival rates were compared, and postoperative complications were assessed. RESULTS: Complete follow-up data were available for 33 patients. The mean follow-up period was 12.2±3.6 (range: 9-32) months and the average age was 72.3±4.7 (range: 59-83) years old. There were 20 females and 13 males. Twenty-three patients had undergone IMN and 10 DHS, according to bone defects and the patient's overall condition. The median survival time was 10 months in the IMN group and 11 months in the DHS group. Duration of surgery (t=-7.366, P<0.001) and length of hospital stay (t=-3.509, P<0.001) differed significantly between the two groups. There was one case of breakage of internal fixation in the IMN group. CONCLUSIONS: There was no significant difference between DHS and IMN in terms of surgical efficacy. IMN and DHS were different in terms of surgical time and hospital stay. However, due to the limited number of cases in this study, multi-factor analysis has not been performed and needs to be further verified in future analysis. When developing a surgical plan, it is recommended to consider the patient's condition and the surgeon's experience.