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Objective The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique—“the medially pedicled IPFP flap”—for reducing postoperative pain, wound complications, and improving functional recovery after TKA. Methods A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C‐reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow‐up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t‐tests were used to compare continuous data and chi‐squared tests were used to compare categorical data between groups. Results Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p

Abstract. Background:. Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Methods:. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results:. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. Conclusions:. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

ObjectivesMusculoskeletal pain after COVID-19 infection remains a concerning long-term complication of COVID-19. Here, our study aimed to investigate the prevalence of musculoskeletal pain associated with COVID-19 (MSPC) and healthcare-seeking behaviors, as well as the associating factors.MethodsA cross-sectional survey was conducted using convenience sampling and distributed to participants anonymously through the online platform Credamo. Demographic and characteristic data of the participants were collected and analyzed. Logistic regression analysis was employed to investigate potential factors associated with MSPC and healthcare-seeking tendencies.ResultsA total of 1,510 participants responded to the survey, with 42.6% (643 individuals) exhibiting MSPC. Higher education level and a greater number of concomitant symptoms were significant risk factors for MSPC, while longer exercise duration and higher PSS-10 scores were protective factors. Additionally, higher income level, frequency and severity of pain, and greater PSS-10 scores increased healthcare-seeking intention.ConclusionA significant proportion of individuals experience MSPC. Education level and concomitant symptoms were risk factors for MSPC, while exercise duration and PSS-10 score were potential protective factors. Income level, frequency and severity of pain, and PSS-10 score are significantly related to the willingness to seek medical treatment for MSPC.

Abstract Fruit ripening is associated with the degreening process (loss of chlorophyll) that occurs in most fruit species. Kiwifruit is one of the special species whose fruits may maintain green flesh by accumulating a large amount of chlorophyll even after ripening. However, little is known about the genetic variations related to the fruit degreening process. Here, a graph‐based kiwifruit pangenome by analyzing 14 chromosome‐scale haplotype‐resolved genome assemblies from seven representative cultivars or lines in Actinidia chinensis is built. A total of 49,770 non‐redundant gene families are identified, with core genes constituting 46.6%, and dispensable genes constituting 53.4%. A total of 84,591 non‐redundant structural variations (SVs) are identified. The pangenome graph integrating both reference genome sequences and variant information facilitates the identification of SVs related to fruit color. The SV in the promoter of the AcBCM gene determines its high expression in the late developmental stage of fruits, which causes chlorophyll accumulation in the green‐flesh fruits by post‐translationally regulating AcSGR2, a key enzyme of chlorophyll catabolism. Taken together, a high‐quality pangenome is constructed, unraveled numerous genetic variations, and identified a novel SV mediating fruit coloration and fruit quality, providing valuable information for further investigating genome evolution and domestication, QTL genes function, and genomics‐assisted breeding.

Abstract Actinidia arguta, known as hardy kiwifruit, is a widely cultivated species with distinct botanical characteristics such as small and smooth-fruited, rich in beneficial nutrients, rapid softening and tolerant to extremely low temperatures. It contains the most diverse ploidy types, including diploid, tetraploid, hexaploid, octoploid, and decaploid. Here we report a haplotype-resolved tetraploid genome (A. arguta cv. ‘Longcheng No.2’) containing four haplotypes, each with 40,859, 41,377, 39,833 and 39,222 protein-coding genes. We described the phased genome structure, synteny, and evolutionary analyses to identify and date possible WGD events. K s calculations for both allelic and paralogous genes pairs throughout the assembled haplotypic individuals showed its tetraploidization is estimated to have formed ~ 1.03 Mya following Ad-α event occurred ~ 18.7 Mya. Detailed annotations of NBS-LRRs or CBFs highlight the importance of genetic variations coming about after polyploidization in underpinning ability of immune responses or environmental adaptability. WGCNA analysis of postharvest quality indicators in combination with transcriptome revealed several transcription factors were involved in regulating ripening kiwi berry texture. Taking together, the assembly of an A. arguta tetraploid genome provides valuable resources in deciphering complex genome structure and facilitating functional genomics studies and genetic improvement for kiwifruit and other crops. Graphical Abstract

BackgroundInflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR.MethodsTwo-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn’s disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability.ResultWith our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk.ConclusionIn a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.

Abstract Background The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. Results In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. Conclusions In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Abstract Background Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. Results In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9–16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°–25°), 40 (13.8%) moderate (25°–50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07–1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4–3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23–40) postoperatively. Conclusion The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Abstract Homogenous transition-metal catalysts bearing a chiral ligand are widely used for asymmetric hydrogenation of unsaturated compounds such as olefins and ketones, providing efficient concise access to products with chiral carbon centers. However, distinguishing the re and si prochiral faces of a double bond bearing two substituents that are sterically and electronically similar is challenging for these catalysts. Herein, we report a relay strategy for constructing compounds with a chiral gem-diaryl carbon center by means of a combination of selective arene exchange between 1,1-diarylethylenes or benzophenones with (naphthalene)Cr(CO)3 and subsequent asymmetric hydrogenation. During the hydrogenation, the Cr(CO)3 unit facilitate differentiation of the two prochiral faces of the substrate double bond via formation of a three-dimensional complex with one of the aromatic rings by selective arene exchange. Density functional theory calculations reveal that during the hydrogenation, chromium coordination affected π–π stacking of the substrate and the catalyst ligand, leading to differentiation of the prochiral faces.

Abstract Actinidia eriantha is a characteristic fruit tree featuring with great potential for its abundant vitamin C and strong disease resistance. It has been used in a wide range of breeding programs and functional genomics studies. Previously published genome assemblies of A. eriantha are quite fragmented and not highly contiguous. Using multiple sequencing strategies, we get the haplotype-resolved and gap-free genomes of an elite breeding line “Midao 31” (MD), termed MDHAPA and MDHAPB. The new assemblies anchored to 29 pseudochromosome pairs with a length of 619.3 Mb and 611.7 Mb, as well as resolved 27 and 28 gap-close chromosomes in a telomere-to-telomere (T2T) manner. Based on the haplotype-resolved genome, we found that most alleles experienced purifying selection and coordinately expressed. Owing to the high continuity of assemblies, we defined the centromeric regions of A. eriantha, and identified the major repeating monomer, which is designated as Ae-CEN153. This resource lays a solid foundation for further functional genomics study and horticultural traits improvement in kiwifruit. Graphical Abstract

Objectives: This study aims to investigate the biomechanical properties of fracture resistance in cracked teeth using five different full-coverage restorations made of three different materials.Materials and Methods: A 3D model of a mandibular first molar was created to design five different full-coverage repair models: crown, crown with composite resin filling inside, occlusal veneer, occlusal veneer with composite resin filling inside and onlay. These repair models were fabricated using three different materials, namely, zirconia, lithium disilicate (LDS), and a hybrid polymer-infiltrated ceramic network material (PIC). In total, 15 repair models were tested using the extended finite element method (XFEM), with an occlusal load of 5000 N applied slowly to the occlusal surface of the restoration. The analysis of stress distribution in the restoration and dentin crack line was conducted to measure and record the crack initial load on the restoration and dentin.Results: The results showed that restorations on the occlusal surface significantly improved crack resistance, with zirconia exhibiting superior fracture resistance among the materials tested. Restorations of crown with composite resin filling inside demonstrated the highest resistance to fracture, while occlusal veneers showed the lowest. MPS concentration was observed at the interface between the restoration and dentin and at the root bifurcation, with the highest values at the top of crack development. Dentin covered by oxidized restorations had the highest displacement, while PIC restorations exhibited the lowest. Pulp analysis revealed selective MPS concentration and strain patterns in models with zirconia restorations and onlay, with pronounced pulp displacement in zirconia restorations and onlay. Enamel analysis indicated larger MPS values and displacements in zirconia restoration models and onlay, with higher strain in onlay. Restoration played a crucial role in protecting the tooth, with crack propagation initial loads in dentin surpassing restorations in experimental groups.Conclusion: This study confirms that full-coverage restorations significantly increased the fracture resistance of cracked teeth, with zirconia restorations significantly protecting the underlying cracked tooth. Elimination of fracture lines in the restoration design can improve fracture resistance in cracked teeth. The findings have implications for dental prosthetic design and clinical practice.

Continuous co-phase traction power system is an effective method to eliminate neutral sections and provide high quality power for both the public grid and the catenary. The substations have the ability to provide cooperative support to each other to reduce capacity and improve system reliability. A fast power control method for substations is needed due to rapid load changes and low overload capability of the system. This paper proposes a fast power control method based on high-speed communication between substations, with additional transient power control to significantly improve the dynamic response of the system.

Summary: Background: A reliable risk prediction model is critically important for identifying individuals with high risk of developing lung cancer as candidates for low-dose chest computed tomography (LDCT) screening. Leveraging a cutting-edge machine learning technique that accommodates a wide list of questionnaire-based predictors, we sought to optimize and validate a lung cancer prediction model. Methods: We developed an Optimized early Warning model for Lung cancer risk (OWL) using the XGBoost algorithm with 323,344 participants from the England area in UK Biobank (training set), and independently validated it with 93,227 participants from UKB Scotland and Wales area (validation set 1), as well as 70,605 and 66,231 participants in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO) control and intervention subpopulations, respectively (validation sets 2 & 3) and 23,138 and 18,669 participants in the United States National Lung Screening Trial (NLST) control and intervention subpopulations, respectively (validation sets 4 & 5). By comparing with three competitive prediction models, i.e., PLCO modified 2012 (PLCOm2012), PLCO modified 2014 (PLCOall2014), and the Liverpool Lung cancer Project risk model version 3 (LLPv3), we assessed the discrimination of OWL by the area under receiver operating characteristic curve (AUC) at the designed time point. We further evaluated the calibration using relative improvement in the ratio of expected to observed lung cancer cases (RIEO), and illustrated the clinical utility by the decision curve analysis. Findings: For general population, with validation set 1, OWL (AUC = 0.855, 95% CI: 0.829–0.880) presented a better discriminative capability than PLCOall2014 (AUC = 0.821, 95% CI: 0.794–0.848) (p

ObjectivesMusculoskeletal pain (MSP) is a major reason for consultation in primary care and is becoming increasingly prevalent among medical students. There is little research on the current situation of MSP among Chinese medical and dental students. Data on the analysis of risk factors related to MSP are also limited. The objectives of this study were to investigate the prevalence and characteristics of MSP among Chinese medical and dental students and to explore the risk factors for MSP and students' intent to seek medical treatment.MethodsAn anonymous, internet-based, cross-sectional, open survey was distributed to medical and dental students at Fujian Medical University, Fuzhou, China. Data on the demographic information and characteristics of MSP were collected and analyzed. In addition to descriptive statistics, logistic regression was used to analyze significant risk factors contributing to MSP.ResultsA total of 1,178 students responded to the survey (response rate = 79.6%), including 722 medical students and 456 dental students. The age ranged from 16 to 24. There were 553 male students and 625 female students. A total of 523 students reported neck pain (NP, 44.4%), 361 students reported low back pain (LBP, 30.6%), and 182 students reported joint pain (JP, 15.4%). Sixty-six students (5.6%) simultaneously suffered from NP, LBP, and JP. The prevalence of NP (49.1 vs. 41.4%, P = 0.01), LBP (34.6 vs. 28.1%, P = 0.02), and JP (20.2 vs. 12.5%, P < 0.001) was significantly higher in dental students than in medical students. The prevalence of MSP was significantly different among the academic years for NP and LBP (P = 0.02 and P < 0.001, respectively). Univariate and multivariate regression analyses demonstrated that female sex, PSS-10 score, and major of stomatology were risk factors for MSP. Medical and dental students' intention to seek treatment for MSP was low and was significantly associated with the severity of pain.ConclusionsThe prevalence of MSP in Chinese medical and dental students is high, especially for NP and LBP, and is significantly higher in dental students than in medical students. The prevalence of NP and LBP were significantly different among academic grades. Female sex, PSS-10 score, and major of stomatology were risk factors for MSP. Students' intent to seek treatment for MSP was very low and was determined by the severity of pain.

BackgroundFungal osteoarticular infection (FOI) is not commonly seen in clinical practice but proposes a great challenge to orthopedic surgeons. In this study, we aimed to investigate the risk factors, the clinical features, and surgical outcomes of FOI in our institution. Specifically, we aimed to explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of FOI.MethodsAll the patients who were diagnosed and managed with FOI in our institution from January 2007 to December 2020 were retrospectively reviewed, including primary fungal implant-related infection, primary fungal osteomyelitis or arthritis, and fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. The potential risk factors and the clinical and surgical features were analyzed. The pathogen data were compared between culture and the mNGS test.ResultsA total of 25 patients were included, namely, 12 primary implant-related infections, 7 primary fungal osteomyelitis or arthritis, and 6 fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. Most cases had undergone multiple surgeries or long-term antibiotic treatment. Diagnosis was mainly based on microbial culture and the mNGS test. Optimization of culture methods and the use of mNGS assisted the diagnosis. Specifically, mNGS was performed in 12 patients, 5 of whom were culture-negative. In the remaining seven cases, mNGS demonstrated the same results as culture. Management of FOI was complicated as most patients required multiple surgeries followed by long-term antifungal treatment. In selected cases, antifungal-impregnated cement spacer retention can be an optional choice. The overall success rate was 100% (25/25) for our cohort.ConclusionWe concluded that patients with comorbidities and a history of multiple surgeries or long-term antibiotics are under higher risk for FOI. Use of mNGS assists the diagnosis and treatment of FOI. Surgery combined with long-term antifungal treatment achieved satisfactory outcomes. In selected cases, antifungal-impregnated cement spacer retention can be an optional treatment choice.

Osteoarthritis (OA) is a debilitating joint disease that affects millions of individuals. The pathogenesis of OA has not been fully elucidated. Obesity is a well-recognized risk factor for OA. Multiple studies have demonstrated adipokines play a key role in obesity-induced OA. Increasing evidence show that various adipokines may significantly affect the development or clinical course of OA by regulating the pro/anti-inflammatory and anabolic/catabolic balance, matrix remodeling, chondrocyte apoptosis and autophagy, and subchondral bone sclerosis. Several signaling pathways are involved but still have not been systematically investigated. In this article, we review the cellular and molecular mechanisms of adipokines in OA, and highlight the possible signaling pathways. The review suggested adipokines play important roles in obesity-induced OA, and exert downstream function via the activation of various signaling pathways. In addition, some pharmaceuticals targeting these pathways have been applied into ongoing clinical trials and showed encouraging results. However, these signaling pathways are complex and converge into a common network with each other. In the future work, more research is warranted to further investigate how this network works. Moreover, more high quality randomised controlled trials are needed in order to investigate the therapeutic effects of pharmaceuticals against these pathways for the treatment of OA. This review may help researchers to better understand the pathogenesis of OA, so as to provide new insight for future clinical practices and translational research.

CAD/CAM (computer-aided design and computer-aided manufacturing) technology has been widely applied in clinical dentistry, but the material safety remains a concern. To investigate the impacts of CAD/CAM metallic materials on trace metals and biocompatibilities, selective laser melted (SLM) cobalt-chromium (Co-Cr) alloys and computer numeric controlled milled (CNC milled) commercially pure titanium (CP-Ti) were placed on the maxilla of beagle dogs for 6 months. The trace metals in the oral mucosa, blood, liver, kidney, and hair were then determined by inductively coupled plasma mass spectrometry (ICP-MS). The histopathologic changes and biocompatibilities of tissues were examined by hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) method, immunohistochemistry (IHC) assay, Western blot analysis, and liver and kidney function tests. Our results showed that trace metals released from these two CAD/CAM metallic materials accumulated transiently in the oral mucosa and whole blood. The trace metals released from SLM Co-Cr alloys could also transiently accumulate in the plasm and hair. In addition, these two CAD/CAM metallic materials both induced apoptosis and histopathologic changes in the oral mucosa, with SLM Co-Cr alloys inducing a higher level of apoptosis. In contrast, both materials did not exert autophagic effects on the oral mucosa or affect the trace metals, functions, or biocompatibilities of the liver and kidney. Therefore, this study suggests that CAD/CAM metallic materials should be selected carefully, especially in patients with metal- and apoptosis-related diseases, and CNC-milled CP-Ti can be recommended to patients on account of its better biocompatibility and safety.

Whether joint replacement surgery can be performed safely on HIV patients is still a matter of debate. This study aimed to report the surgical efficacy and complications of joint replacement surgery in HIV patients. A total of 21 HIV patients and 27 non-HIV patients who underwent arthroplasties in our hospital were retrospectively reviewed. The 21 HIV patients received 29 joint replacement surgeries including 27 cases of total hip arthroplasty (THA) and 2 cases of total knee arthroplasty (TKA). The non-HIV patients received 16 THA, 10 TKA, and 3 unicompartmental arthroplasty (UKA). The length of hospital stay of HIV patients was significantly lower than that of non-HIV patients. At the last follow-up, there were no significant complications both in the HIV group and the non-HIV groups. No medical staff had any occupational exposure. We concluded that joint replacement surgery in HIV patients is safe and effective. Optimization of patients is key to treatment success. Strictly following the standardized protection protocol can prevent the risk of occupational exposure.

This study aims to explore the quality of life (QOL) and pain after revision surgery for periprosthetic joint infection (PJI) based on patients’ reported outcomes. A cross-sectional questionnaire survey was conducted and 137 valid responses were included (response rate 64.0%). A total of 42 patients underwent debridement with implant retention (DAIR), 31 underwent one-stage revision, and 64 underwent two-stage revision. The average overall SF-36 score was 70.3. The DAIR group had significantly higher SF-36 than the two-stage revision group (p = 0.01). There was no significant difference between the one-stage revision group and the other two groups. A total of 74.5% of patients reported pain with an average McGill Pain Questionnaire (MPQ) score of 8.6. There was no significant difference in the MPQ scores among the three groups. Simple linear regression analyses demonstrated that higher preoperative PMN%, VAS, and shorter hospital stay were associated with pain (adjusted R2 = 4%, p = 0.020; adjusted R2 = 2.1%, p = 0.048; adjusted R2 = 2.1%, p = 0.049; respectively). We concluded that the overall QOL of patients after revision surgery for PJI is generally satisfactory. Persistent pain is prevalent, but the severity was mostly mild. Preoperative PMN%, VAS, and hospital stay were associated with postoperative pain.

Responder analysis is in common use in clinical trials, and has been described and endorsed in regulatory guidance documents, especially in trials where “soft” clinical endpoints such as rating scales are used. The procedure is useful, because responder rates can be understood more intuitively than a difference in means of rating scales. However, two major issues arise: 1) such dichotomized outcomes are inefficient in terms of using the information available and can seriously reduce the power of the study; and 2) the results of clinical trials depend considerably on the response cutoff chosen, yet in many disease areas there is no consensus as to what is the most appropriate cutoff. This article addresses these two issues, offering a novel approach for responder analysis that could both improve the power of responder analysis and explore different responder cutoffs if an agreed-upon common cutoff is not present. Specifically, we propose a statistically rigorous clinical trial design that pre-specifies multiple tests of responder rates between treatment groups based on a range of pre-specified responder cutoffs, and uses the minimum of the p-values for formal inference. The critical value for hypothesis testing comes from permutation distributions. Simulation studies are carried out to examine the finite sample performance of the proposed method. We demonstrate that the new method substantially improves the power of responder analysis, and in certain cases, yields power that is approaching the analysis using the original continuous (or ordinal) measure.

Motivated by the challenges in assessing physician-level cancer screening performance and the negative impact of misclassification, we propose a method (using mammography as an example) that enables confident assertion of adequate or inadequate performance or alternatively recognizes when more data is required.Using established metrics for mammography screening performance-cancer detection rate (CDR) and recall rate (RR)-and observed benchmarks from the Breast Cancer Surveillance Consortium (BCSC), we calculate the minimum volume required to be 95% confident that a physician is performing at or above benchmark thresholds. We graphically display the minimum observed CDR and RR values required to confidently assert adequate performance over a range of interpretive volumes. We use a prospectively collected database of consecutive mammograms from a clinical screening program outside the BCSC to illustrate how this method classifies individual physician performance as volume accrues.Our analysis reveals that an annual interpretive volume of 2770 screening mammograms, above the United States' (US) mandatory (480) and average (1777) annual volumes but below England's mandatory (5000) annual volume is necessary to confidently assert that a physician performed adequately. In our analyzed US practice, a single year of data uniformly allowed confident assertion of adequate performance in terms of RR but not CDR, which required aggregation of data across more than one year.For individual physician quality assessment in cancer screening programs that target low incidence populations, considering imprecision in observed performance metrics due to small numbers of patients with cancer is important.

In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P=0.002) and tumor growth (P