Honghua Xiaoyao tablet combined with estradiol improves ovarian function in D-galactose-induced aging mice by reducing apoptosis and affecting the release of reproductive hormones: an in vivo study.

Context: It is very necessary to delay ovarian aging and prevent age-related health problems. The active ingredient in Honghua Xiaoyao tablet (HHXYT) has the effects of anti-oxidation, anti-inflammation, immune regulation and so on. Objective: To explore the effect and mechanism of Honghua Xiaoyao tablet on aging model mice. Materials and methods: The aging model was established by intraperitoneal injection of D-galactose in model mice. The mice in the HHXYT-L,M,H group were given 0.3 g/kg, 0.6 g/kg and 1.2 g/kg Honghua Xiaoyao tablet suspension respectively, and the HHXYT-M + E2 group was given 0.6 g/kg HHXYT +0.13 mg/kg estradiol valerate for 30 days. In this study, ELISA, HE, Western blot, IH and TUNEL were used. Results: HHXYT + E2 can improve the gonadal index, estrous cycle of aging mice. In HHXYT-M + E2 group, the level of FSH and LH decreased, while E2 and AMH increased significantly. The number of growing follicles in HHXYT-M + E2 group increased, which was better than that of HHXYT alone. Western blot results showed that HHXYT-M + E2 group decreased the expression of Bax, cleaved-Parp, cleaved-Casp-3 and CytC molecules and increased the expression of Bcl-2 in ovarian tissue. FSHR expression decreased in model group and increased in HHXYT group. TUNEL staining showed that the number of apoptotic cells in HHXYT group was reduced, and the HHXYT-M + E2 group was the most significantly. Discussion and conclusion: HHXYT can improve the level of sex hormones and increase the number of growing follicles in aging mice. HHXYT-M + E2 group has the best effect, and its mechanism may be related to reducing ovarian granulosa cell apoptosis.

Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren-Lawrence Grades II-III.

This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 (p < 0.05) and from 68.4 to 83.3 points (p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.

Mechanical Activation of Graphite for Na-Ion Battery Anodes: Unexpected Reversible Reaction on Solid Electrolyte Interphase via X-Ray Analysis.

Although sodium-ion batteries (SIBs) offer promising low-cost alternatives to lithium-ion batteries (LIBs), several challenges need to be overcome for their widespread adoption. A primary concern is the optimization of carbon anodes. Graphite, vital to the commercial viability of LIBs, has a limited capacity for sodium ions. Numerous alternatives to graphite are explored, particularly focusing on disordered carbons, including hard carbon. However, compared with graphite, most of these materials underperform in LIBs. Furthermore, the reaction mechanism between carbon and sodium ions remains ambiguous owing to the structural diversity of disordered carbon. A straightforward mechanical approach is introduced to enhance the sodium ion storage capacity of graphite, supported by comprehensive analytical techniques. Mechanically activated graphite delivers a notable reversible capacity of 290.5 mAh·g-1 at a current density of 10 mA·g-1. Moreover, it maintains a capacity of 157.7 mAh·g-1 even at a current density of 1 A·g-1, benefiting from the defect-rich structure achieved by mechanical activation. Soft X-ray analysis revealed that this defect-rich carbon employs a sodium-ion storage mechanism distinct from that of hard carbon. This leads to an unexpected reversible reaction on the solid electrolyte surface. These insights pave the way for innovative design approaches for carbon electrodes in SIB anodes.

Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

BACKGROUND: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. METHODS: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). RESULTS: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. CONCLUSION: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Dingkun Pill modulate ovarian function in chemotherapy-induced premature ovarian insufficiency mice by regulating PTEN/PI3K/AKT/FOXO3a signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. AIM OF THE STUDY: To investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. MATERIALS AND METHODS: Fifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). RESULTS: In POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. CONCLUSIONS: The Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.

Preoperative Dyeing Technique for Decreasing Radiation Exposure in Unilateral Biportal Endoscopic Spine Surgery.

BACKGROUND: Minimally invasive surgery has many advantages, including early recovery and cosmetic preservation. However, the higher radiation exposure to physicians and patients has drawbacks. Preoperative tissue dyeing techniques are feasible options for reducing radiation exposure and procedure time, but their efficacy has not yet been evaluated. Therefore, this study aimed to evaluate surgical outcomes and reduce radiation exposure during unilateral biportal endoscopy surgery. METHODS: This was a prospective, case-controlled analysis in a tertiary hospital. Patients receiving experimental tissue dye and controls in the nondye group were compared from May 2020 to September 2021. The ipsilateral posterolateral approach (IPA) and the far lateral approach (FLA) were analyzed separately among all single-level spinal procedures without instrumentation. Operative details (operation time, improvement of back and leg pain, and length of hospital stay) and radiation exposure (dose and duration) were compared. RESULTS: A total of 88 cases were included, consisting of 64 interlaminar approaches (experimental: 33, control: 31) and 24 FLAs (experimental: 13 and control: 11). In the IPA approach, the patient and physician radiation exposure doses and duration decreased significantly. Conversely, for the FLA, only the duration of the physician exposure decreased significantly. CONCLUSIONS: Preoperative tissue dyeing techniques using IPA can reduce radiation exposure for physicians and patients. However, a decrease in the duration of radiation was observed only in physicians using the FLA. The dyeing technique is effective in IPA, but the efficacy of FLA is doubtful.

Tibial Post Refracture in Posterior-Stabilized Total Knee Arthroplasty Following Isolated Tibial Insert Exchange.

Background: We report 4 cases with a tibial post refracture following isolated tibial insert exchange in posterior-stabilized total knee arthroplasty at a single center. Methods: In our institution, 27 cases (26 patients) underwent reoperation due to tibial post fracture in posterior-stabilized total knee arthroplasty between July 2008 and November 2020. Of these 27 cases, 4 (4 patients) tibial post refractures occurred at a mean follow-up period of 9.1 years. Results: All 4 cases of tibial post refracture occurred in a group of 21 cases with isolated tibial insert exchange. There was no tibial post refracture in patients with a tibial revision surgery. The incidence of this complication following isolated tibial insert exchange was 19.0%. The mean elapsed time from tibial insert exchange to the diagnosis of a post refracture was 2.5 years (range: 1.1-6.6 years). Conclusions: Isolated exchange of a tibial insert with excessive thickness as a treatment for tibial post fracture is associated with a high probability of tibial post refracture. The treatment method should be selected after a thorough analysis according to the cause of fracture. Level of evidence: IV.

No higher tibial post fracture rate with highly cross-linked polyethylene inserts in total knee arthroplasty at a minimum 10-year follow-up.

PURPOSE: The purpose of this study was to assess tibial post fracture between highly cross-linked polyethylene (HXPE) and conventional polyethylene inserts in consecutive posterior-stabilized (PS) total knee arthroplasty (TKA) over a minimum 10-years follow-up period. METHODS: Between July 2008 and December 2011, a consecutive series of 3264 primary TKAs was performed in 2098 patients using a PS total knee prosthesis at a single institution. The final cohort was classified into the HXPE group (792 cases) and the conventional group (2113 cases) according to insert material used during the procedure. RESULTS: The mean follow-up period was 11.4 years in the HXPE group and 11.8 years in the conventional group. Both cases of tibial post fracture occurred in the HXPE group, a complication rate of 0.25%. These two cases required replacement with a thicker tibial insert with retention of the femoral and tibial components. There were no cases of tibial post fracture in the conventional group. CONCLUSION: There was no difference in tibial post fracture rate between the HXPE group and the conventional group in PS TKA on long-term follow-up. LEVEL OF EVIDENCE: IV.

Distal Femoral Pin Tracker Placement Prevents Pin Tract-induced Fracture in Robotic-Assisted Total Knee Arthroplasty.

The purpose of this study was to determine the effectiveness of the placement of pin trackers in the medial sagittal plane of the distal femur in robotic-assisted total knee arthroplasty (TKA) over a minimum follow-up period of 3 months. From August 2020 to October 2020, a consecutive series of 81 TKAs were performed in 59 patients using the Triathlon posterior-stabilized total knee prosthesis with a robotic-assisted system (Mako) at our hospital. Patient charts were reviewed for complications associated with the pin sites, including fracture, infection, thigh pain, and the need for reoperation. No patients had any minor or major complications associated with distal femoral pins. This technique, which used pin trackers in the medial sagittal plane of the distal femur, could be a useful option for surgeons performing robotic-assisted TKA. This is a Level IV study.

Distal Femoral Tracker Pin Placement Prevents Delayed Pin Tract-Induced Fracture in Robotic-Assisted Total Knee Arthroplasty: Results of Minimum 1-Year Follow-Up.

The purpose of this study was to determine the outcomes of the placement of a pin tracker in the distal femur in robotic-assisted total knee arthroplasty (TKA) over a minimum follow-up period of 1 year. A consecutive series of 81 TKAs were performed in 59 patients using a robotic-assisted system (Mako) at our hospital. The mean follow-up period was 1.1 years (range, 1-1.2 years). No periprosthetic fracture at a pin tracker site was reported at a minimum of 1 year of follow-up. No patients reported minor or major complications associated with the distal femoral pins. In addition, unicortical pin-site drilling marks in all patients disappeared on one-postoperative-year follow-up radiographs. Our technique, which used unicortical pin placement in the distal femur in robotic-assisted TKA, demonstrated that it was a safe and reliable method at a minimum follow-up period of 1 year. The level of evidence is IV.

Long-term outcomes of total knee arthroplasty in patients with windswept deformity.

BACKGROUND: This study compared the functional outcomes, implant survival rates, and complications of total knee arthroplasty (TKA) performed in patients with windswept deformity (WSD) and non-WSD patients over at least 10 years of follow-up. METHODS: From January 2008 to December 2010, 40 TKAs were performed in 20 patients with WSD (WSD group). Additionally, 60 propensity score-matched patients without WSD who had undergone primary bilateral TKA were chosen for the control group in a three-to-one ratio. Then, the functional outcomes, implant survival rates, and complications of TKA in the two groups were compared. The mean follow-up periods were 10.8 years in the WSD group and 11.5 years in the control group. RESULTS: The mean Knee Society knee scores in the WSD and control groups improved from 37.7 to 38.1 points preoperatively to 79.5 and 79.2 points at final follow-up (p = 0.974), while the mean function scores in the WSD and control groups improved from 36.5 to 37.2 points preoperatively to 77.8 and 77.4 points at final follow-up (p = 0.863). Two knees in the WSD group required revision surgery, including one due to septic loosening and one due to aseptic loosening. Five knees in the control group required revision surgery, including three due to septic loosening and two due to aseptic loosening. Kaplan-Meier survivorship analysis with the revision of either component as an endpoint in the WSD and control groups estimated 95.0% and 95.8% chances of survival for 10 years, respectively (p = 0.824). CONCLUSIONS: TKA performed in patients with WSD yielded good clinical outcomes and survivorship at least 10 years later. LEVEL OF EVIDENCE: IV.

Percutaneous Biportal Endoscopic Fenestration for Symptomatic Foraminal Tarlov Cyst.

Perineural (Tarlov) cysts are a common benign pathology in the lumbosacral area but are rarely symptomatic, even when compressing the spinal root. Despite the rarity of Tarlov cyst formation in the foramen of the spine, this type is more symptomatic than those in other sites due to the narrow space. We introduce a biportal endoscopic fenestration for symptomatic foraminal Tarlov cysts. We present the case of a 40-year-old woman experiencing radiating pain in her right lower leg for 4 years. On seeking treatment, her great toe and ankle plantar flexion power had decreased. Magnetic resonance imaging revealed a cystic mass located in the L5-S1 intervertebral foramen that compressed the lumbar nerve root. Partial laminotomy was performed using a percutaneous biportal endoscopic system with a far lateral approach. An oval cystic mass of 2.6×1.1 cm was identified on high-definition images. Partial bone and foraminal ligament removal and cystic membrane fenestration were performed for nerve decompression. After decompression, the patient's motor weakness and radiating pain improved. Due to high-definition images and the minimally invasive laminotomy procedures associated with percutaneous biportal endoscopic fenestration, a foraminal Tarlov cyst was fenestrated safely, and weakness arising from radiculopathy was resolved in the current case. [Orthopedics. 2023;46(2):e125-e128.].

Early aseptic loosening of primary total knee arthroplasty in patients with osteonecrosis of the knee: A case series.

The cause of early aseptic loosening in total knee arthroplasty (TKA) is uncertain, although several possibilities could be offered. We report that osteonecrosis of the knee should be considered as a possible cause or contributing etiologic factor for early aseptic loosening following primary TKA.

Coronal Correction for Post-Traumatic Malalignment Using Robot-Assisted Total Knee Arthroplasty: A Case Series.

Background: Achieving proper axis alignment can be difficult in the presence of posttraumatic extra-articular deformities in either the femur or the tibia. We present radiological outcomes following robot-assisted total knee arthroplasty (TKA) in patients with osteoarthritis of the knee accompanied by posttraumatic extra-articular deformities. Methods: We analyzed the outcomes of five knees in five patients with (1) Kellgren-Lawrence (K-L) Grade III-IV osteoarthritic knees, (2) the presence of posttraumatic extra-articular deformities either in the femur or the tibia, and (3) who underwent robot-assisted TKA. Their radiological findings were evaluated. Results: All five knees with initial deformity (mean 14.8°, range 12.7-18.5°) were corrected to neutral alignment (mean 0.7°, range -1.1-2.7°). There was no postoperative outlier of hip-knee-ankle (HKA) angle. Conclusion: Our results indicate that robot-assisted TKA can be used to achieve proper limb alignment in patients with posttraumatic extra-articular deformities.

Robot-assisted total knee arthroplasty improves mechanical alignment and accuracy of component positioning compared to the conventional technique.

PURPOSE: The purpose of this study was to compare the mechanical axis, accuracy of component positioning, and polyethylene liner thickness between robot-assisted total knee arthroplasty (TKA) and conventional TKA. METHODS: From July 2020 to December 2020, 154 TKAs were performed in 110 patients with Kellgren-Lawrence grade IV varus knees using a robot-assisted system (MAKO group). Additionally, 110 propensity score-matched patients who had undergone primary conventional TKA were chosen in a one-to-one ratio for the conventional group. Post-operative radiographs were used to evaluate mechanical axis and component coronal and sagittal positioning. The polyethylene liner thickness was investigated. The respective mean error values and outliers were obtained for the two study groups and were compared to determine the mechanical axis and the accuracy of the postoperative component positioning. RESULTS: Patients in the MAKO group achieved better accuracy than those in the conventional group in terms of postoperative mean mechanical axis (1.9˚ vs. 2.8˚, p < 0.05), femur coronal inclination (91.2˚ vs. 91.8˚, p < 0.05), tibia coronal inclination (90.8˚ vs. 91.1˚, p < 0.05), and tibia sagittal inclination (90.7˚ vs. 91.7˚, p < 0.05). However, there was no difference between the two groups in polyethylene liner thickness. CONCLUSIONS: Robot-assisted TKA showed improved mechanical axis and higher accuracy of component positioning compared to the conventional TKA technique, with no significant difference in polyethylene liner thickness between the two groups. Long-term follow-up studies are needed to compare the clinical outcomes of robot-assisted TKA. LEVEL OF EVIDENCE: IV.

Association between visit-to-visit blood pressure variability and adverse events in coronary artery disease patients after coronary intervention.

Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty-two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non-fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre-PCI and post-PCI BPV were associated with CV events even after adjusting for co-morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03-1.05), 1.04 (95%CI: 1.02-1.05), 1.05 (95%CI: 1.04-1.06), and 1.06 (95%CI: 1.03-1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre-PCI and post-PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

Cordycepin (3'-Deoxyadenosine) Suppresses Heat Shock Protein 90 Function and Targets Tumor Growth in an Adenosine Deaminase-Dependent Manner.

Alterations in metabolism and energy production are increasingly being recognized as important drivers of neoplasia, raising the possibility that metabolic analogs could disrupt oncogenic pathways. 3'-deoxyadenosine, also known as cordycepin, is an adenosine analog that inhibits the growth of several types of cancer. However, the effects of cordycepin have only been examined in a limited number of tumor types, and its mechanism of action is poorly understood. We found that cordycepin slows the growth and promotes apoptosis in uveal melanoma, as well as a range of other hard-to-treat malignancies, including retinoblastoma, atypical teratoid rhabdoid tumors, and diffuse midline gliomas. Interestingly, these effects were dependent on low adenosine deaminase (ADA) expression or activity. Inhibition of ADA using either siRNA or pharmacologic approaches sensitized tumors with higher ADA to cordycepin in vitro and in vivo, with increased apoptosis, reduced clonogenic capacity, and slower migration of neoplastic cells. Our studies suggest that ADA is both a biomarker predicting response to cordycepin and a target for combination therapy. We also describe a novel mechanism of action for cordycepin: competition with adenosine triphosphate (ATP) in binding to Hsp90, resulting in impaired processing of oncogenic Hsp90 client proteins.

Usefulness of Trabecular Metal Cones in Revision Total Knee Arthroplasty in a Korean Population: A Case Series.

Purpose: The purpose of this study was to assess the medium-term results of trabecular metal cones for the reconstruction of large bone defects in revision TKA. Methods: Thirteen patients who had undergone revision TKA using trabecular metal cones for femoral and/or tibial large bone defects were identified. We included patients who had a minimum of three years follow-up in the study. We evaluated their functional outcomes, implant survivorship, radiological findings, and complications. Results: At a mean follow-up of 6.9 years (range of 3.5-9.4 years), all trabecular metal cones and implants were well fixed and did not exhibit any radiographic evidence of migration or loosening. At the final follow-up, the mean Knee Society knee scores had improved from 37.2 to 78.1 (p < 0.05), and function scores had improved from 35.5 to 77.5 points (p < 0.05). One intraoperative fracture in the distal femur occurred in an 85-year-old woman during impaction of a single trabecular metal cone. The fracture was successfully affixed to the femoral cone and bone three months postoperatively. Conclusion: The present study of trabecular metal cones demonstrates excellent clinical outcomes and survivorship in revision TKA during medium-term follow-up periods. However, longer-term follow-up studies are needed to further investigate these implants in revision TKA. Additionally, the necessity of metal cones in revision procedures should be carefully considered depending on patient needs and economic capabilities.

pubmedKB: an interactive web server for exploring biomedical entity relations in the biomedical literature.

With the proliferation of genomic sequence data for biomedical research, the exploration of human genetic information by domain experts requires a comprehensive interrogation of large numbers of scientific publications in PubMed. However, a query in PubMed essentially provides search results sorted only by the date of publication. A search engine for retrieving and interpreting complex relations between biomedical concepts in scientific publications remains lacking. Here, we present pubmedKB, a web server designed to extract and visualize semantic relationships between four biomedical entity types: variants, genes, diseases, and chemicals. pubmedKB uses state-of-the-art natural language processing techniques to extract semantic relations from the large number of PubMed abstracts. Currently, over 2 million semantic relations between biomedical entity pairs are extracted from over 33 million PubMed abstracts in pubmedKB. pubmedKB has a user-friendly interface with an interactive semantic graph, enabling the user to easily query entities and explore entity relations. Supporting sentences with the highlighted snippets allow to easily navigate the publications. Combined with a new explorative approach to literature mining and an interactive interface for researchers, pubmedKB thus enables rapid, intelligent searching of the large biomedical literature to provide useful knowledge and insights. pubmedKB is available at https://www.pubmedkb.cc/.

Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification.

MicroRNA-dependent mRNA decay plays an important role in gene silencing by facilitating posttranscriptional and translational repression. Inspired by this intrinsic nature of microRNA-mediated mRNA cleavage, here, we describe a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate the translocation of proteins. We applied the mRNA bridge mimetics platform to Cas9 protein to confer it the ability to translocate into the nucleus via cleavage of the nuclear export signal. This system performed programmed gene editing in vitro and in vivo. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs in vivo. Using the endogenous microRNA-mediated mRNA decay mechanism, our platform is able to remodel a cell's natural biology to allow the entry of precise drugs into the nucleus, devoid of non-specific translocation. The mRNA bridge mimetics strategy is promising for applications in which the reaction must be controlled via intracellular stimuli and modulates Cas9 proteins to ensure safe genome modification in diseased conditions.