Comparison of Novel 3D-printed Stepped Porous Metal Cones and Metaphyseal Sleeves for Reconstruction of Severe Knee Bone Defects: Short-term Clinical Outcomes.

OBJECTIVE: Both porous metal cones and metaphyseal sleeves are excellent implants for reconstructing severe bone defects in the knee joint, but they both exhibit design limitations. The porous metal cone, especially, has significant room for improvement in its shape design. The existing porous metal cones often feature a conical external surface with a relatively small taper, potentially compromising both rotational and axial stability. To improve both axial and rotational stability in porous metal cones, we developed a 3D-printed stepped porous metal cone. This study aimed to assess the short-term clinical outcome of the 3D-printed stepped porous metal cone and to compare it with the clinical outcome of patients who underwent revision total knee arthroplasty (rTKA) with the metaphyseal sleeves during the same period. METHOD: Patients who underwent total knee arthroplasty revision with metaphyseal bone defect reconstruction from 2019 to 2021 were retrospectively analyzed. A total of 61 patients were enrolled in the study, including 15 patients using 3D-printed stepped porous metal cones and 46 patients using metaphyseal metal sleeves. Thirty patients using metaphyseal sleeves were screened by propensity score matching method and compared with those using stepped cones. Analysis included the American Knee Society Score, the Hospital for Special Surgery knee score, the Western Ontario and McMaster Universities Arthritis index, the Short Form 12 (SF-12) health survey, and radiographic assessment with a mean follow-up of 28.5 ± 8.3 months. To conduct comparative analyses, unpaired Student's t-tests were employed for continuous variables, while categorical variables were analyzed using the appropriate Fisher exact or chi-squared test. RESULTS: In this study, the survival rates of both the stepped cone and metaphyseal sleeve were 100%. There was no statistically significant difference in postoperative knee function scores between the two groups (p > 0.05). However, patients in the cone group had significantly higher mental component summary scores on the SF-12 scale (p < 0.05) and higher increases in mean postoperative physical component summary scores than patients in the sleeve group (p < 0.05). In addition, patients in the cone group experienced fewer intraoperative and postoperative complications compared to the sleeve group. CONCLUSION: The 3D-printed stepped porous metal cone can effectively reconstruct bone defects in complex rTKA and provide satisfactory early clinical and radiographic results. The 3D-printed stepped cone provides a more stable structure similar to the sleeve while maintaining the original benefits of the cone making it a promising choice for rTKA.

Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination.

BACKGROUND: Clostridium spp. has demonstrated therapeutic potential in cancer treatment through intravenous or intratumoral administration. This approach has expanded to include non-pathogenic clostridia for the treatment of various diseases, underscoring the innovative concept of oral-spore vaccination using clostridia. Recent advancements in the field of synthetic biology have significantly enhanced the development of Clostridium-based bio-therapeutics. These advancements are particularly notable in the areas of efficient protein overexpression and secretion, which are crucial for the feasibility of oral vaccination strategies. Here, we present two examples of genetically engineered Clostridium candidates: one as an oral cancer vaccine and the other as an antiviral oral vaccine against SARS-CoV-2. RESULTS: Using five validated promoters and a signal peptide derived from Clostridium sporogenes, a series of full-length NY-ESO-1/CTAG1, a promising cancer vaccine candidate, expression vectors were constructed and transformed into C. sporogenes and Clostridium butyricum. Western blotting analysis confirmed efficient expression and secretion of NY-ESO-1 in clostridia, with specific promoters leading to enhanced detection signals. Additionally, the fusion of a reported bacterial adjuvant to NY-ESO-1 for improved immune recognition led to the cloning difficulties in E. coli. The use of an AUU start codon successfully mitigated potential toxicity issues in E. coli, enabling the secretion of recombinant proteins in C. sporogenes and C. butyricum. We further demonstrate the successful replacement of PyrE loci with high-expression cassettes carrying NY-ESO-1 and adjuvant-fused NY-ESO-1, achieving plasmid-free clostridia capable of secreting the antigens. Lastly, the study successfully extends its multiplex genetic manipulations to engineer clostridia for the secretion of SARS-CoV-2-related Spike_S1 antigens. CONCLUSIONS: This study successfully demonstrated that C. butyricum and C. sporogenes can produce the two recombinant antigen proteins (NY-ESO-1 and SARS-CoV-2-related Spike_S1 antigens) through genetic manipulations, utilizing the AUU start codon. This approach overcomes challenges in cloning difficult proteins in E. coli. These findings underscore the feasibility of harnessing commensal clostridia for antigen protein secretion, emphasizing the applicability of non-canonical translation initiation across diverse species with broad implications for medical or industrial biotechnology.

Development of a CRISPR-Cas12a system for efficient genome engineering in clostridia.

IMPORTANCE: Continued efforts in developing the CRISPR-Cas systems will further enhance our understanding and utilization of Clostridium species. This study demonstrates the development and application of a genome-engineering tool in two Clostridium strains, Clostridium butyricum and Clostridium sporogenes, which have promising potential as probiotics and oncolytic agents. Particular attention was given to the folding of precursor crRNA and the role of this process in off-target DNA cleavage by Cas12a. The results provide the guidelines necessary for efficient genome engineering using this system in clostridia. Our findings not only expand our fundamental understanding of genome-engineering tools in clostridia but also improve this technology to allow use of its full potential in a plethora of biotechnological applications.

Refined control of CRISPR-Cas9 gene editing in Clostridium sporogenes: the creation of recombinant strains for therapeutic applications.

Despite considerable clinical success, the potential of cancer immunotherapy is restricted by a lack of tumour-targeting strategies. Treatment requires systemic delivery of cytokines or antibodies at high levels to achieve clinically effective doses at malignant sites. This is exacerbated by poor penetration of tumour tissue by therapeutic antibodies. High-grade immune-related adverse events (irAEs) occur in a significant number of patients (5-15%, cancer- and therapeutic-dependent) that can lead to lifelong issues and can exclude from treatment patients with pre-existing autoimmune diseases. Tumour-homing bacteria, genetically engineered to produce therapeutics, is one of the approaches that seeks to mitigate these drawbacks. The ability of Clostridium sporogenes to form spores that are unable to germinate in the presence of oxygen (typical of healthy tissue) offers a unique advantage over other vectors. However, the limited utility of existing gene editing tools hinders the development of therapeutic strains. To overcome the limitations of previous systems, expression of the Cas9 protein and the gRNA was controlled using tetracycline inducible promoters. Furthermore, the components of the system were divided across two plasmids, improving the efficiency of cloning and conjugation. Genome integrated therapeutic genes were assayed biochemically and in cell-based functional assays. The potency of these strains was further improved through rationally-conceived gene knock-outs. The new system was validated by demonstrating the efficient addition and deletion of large sequences from the genome. This included the creation of recombinant strains expressing two pro-inflammatory cytokines, interleukin-2 (IL-2) and granulocyte macrophage-colony stimulating factor (GM-CSF), and a pro-drug converting enzyme (PCE). A comparative, temporal in vitro analysis of the integrant strains and their plasmid-based equivalents revealed a substantial reduction of cytokine activity in chromosome-based constructs. To compensate for this loss, a 7.6 kb operon of proteolytic genes was deleted from the genome. The resultant knock-out strains showed an 8- to 10-fold increase in cytokine activity compared to parental strains.

Metaphyseal Metal Sleeves for Reconstruction of Severe Knee Bone Defects: Excellent Survival Rate at a Mean Follow-Up of 6.4 Years.

OBJECTIVE: Management of bone loss in complex primary and revision total knee arthroplasty is key to the surgeries. Metaphyseal metal sleeves have been increasingly used recently to reconstruct severe knee metaphyseal bone defects. This study aimed to investigate the outcomes of the metaphyseal sleeve reconstructing Anderson Orthopedic Research Institute (AORI) type II and type III bone defects of knee joint. METHODS: From 2014 to 2019, a total of 44 knees were enrolled in this clinical retrospective study after the screening, including seven cases of primary TKA and 37 cases of revision TKA. The types of bone defects involved in this study were AORI types II and III, and did not involve AORI type I bone defects. Patients' knee function preoperatively and postoperatively as well as quality of life were recorded and analyzed. Analysis included the American Knee Society Score (KSS), hospital for special surgery knee score (HSS), the Western Ontario and McMaster Universities (WOMAC) index, the Short Form 12 (SF-12) health survey, visual analogue scale score, and radiographic assessment with a mean follow-up of 6.4 years. Paired t-tests were used to determine the significance of changes in clinical scores and knee mobility. RESULTS: A mean follow-up of 77.2 (±17.6, standard deviation [SD]) months was performed, and none of the patients underwent knee revision for infection or aseptic loosening. At the last follow-up, the KSS knee score changed statistically from 37.1 (±19.7) preoperatively to 86.5 (±13.6, SD, p < 0.001) postoperatively and the KSS function score from 32.7 (±24.0) preoperatively to 78.3 (±15.6, SD, p < 0.001) postoperatively. The knee mobility improved from a mean of preoperative 72.61° (±33.42°, SD) to 108.52° (±24.15°, SD, p < 0.001). Postoperative radiographs showed that the host bone was tightly integrated with the metaphyseal metal sleeve, and there was no obvious translucent line formation around the sleeve. Of the patients, 86.4% had a postoperative satisfaction score ≥8 (10-point scale). CONCLUSION: At the mean follow-up of 6.4 years, the survival rate of the metaphyseal sleeves was 100%. Metaphyseal sleeves combined with cementless stems is an excellent and viable option for reconstruction of AORI type II and type III bone defects of the knee.

Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.

Distribution and abundance of oil-degrading bacteria in seawater of the Yellow Sea and Bohai Sea, China.

Petroleum hydrocarbons are widespread in seawater. As an important sea area in northern China, the content and distribution of petroleum hydrocarbons in seawater need our attention because of the high toxicity and lasting polluting effects on the ecological environment of the Yellow Sea and Bohai Sea. In addition, there are few reports comparing the diversity of oil-degrading bacteria before and after enrichment. Therefore, we collected surface seawater from 10 sites in the Yellow Sea and Bohai Sea in the autumn of 2020 to study the distribution characteristics of total petroleum hydrocarbons (TPH) and the diversity of oil-degrading bacteria. The concentration of TPH was 81.65 µg/L-139.55 µg/L at ten sites in the Bohai Sea and the Yellow Sea, which conformed to the China Grade II water quality standard (GB3097-1997). Moreover, the pristine/phytane (PR/PH) value of most sites was close to 1, indicating that the area was obviously polluted by exogenous petroleum hydrocarbons. We found that oil-degrading bacteria in the seawater of the Yellow Sea and the Bohai Sea had a good degradation effect on C11-C14 short chain alkanes (degradation rate of 59.19-73.22 %) and C1-C4 phenanthrene (degradation rate of 48.19-60.74 %). In terms of the diversity of oil-degrading bacteria, Gammaproteobacteria and Alphaproteobacteria dominated the enriched bacterial communities. Notably, the relative abundance of Alcanivorax changed significantly before and after enrichment. We proposed that surface seawater in the Bohai Sea and Yellow Sea could form oil-degrading bacteria mainly composed of Alcanivorax, which had great potential for oil pollution remediation.

Diagnosis and treatment of adult patients with PTLD at different sites after liver transplantation: A three-case report and literature review.

Post-transplant lymphoproliferative disease (PTLD) is a rare complication accompanying organ transplantation. Herein, we presented 3 cases of PTLD with different primary sites. All three patients presented with symptoms in the corresponding organs or sites and the latter two patients started with atypical symptoms of infections. The first two patients who developed the disease about a year after liver transplantation both had EBV infections. All three patients received immunosuppressant reduction and antiviral therapy. In case 2, remission occurred midway. Adult liver transplantation recipients are at high risk for PTLD, and screening for EBV infection should be intensified in such recipients within 1 year after liver transplantation. Patients should be highly alert for the development of PTLD when new unidentified masses appear, for whom enhanced CT and tissue biopsy should be performed as early as possible.

Liver transplantation for intrahepatic cholangiocarcinoma: a propensity score-matched analysis.

Liver resection (LR) is the only recommended effective curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis of patients with ICC is still poor even after curative resection. Recently, many researchers focused on the therapeutic value of LT for patients with ICC. This study aimed to identify the role of liver transplantation in patients with ICC by internally comparing with LR in ICC and externally comparing with LT in HCC. We obtained patient data from SEER database. Propensity score methods were applied to control confounders. Survival outcome was estimated using Kaplan-Meier survival curves and compared using the log-rank test. A total of 2538 patients with ICC after surgery and 5048 patients with HCC after LT between 2000 and 2019 were included in this study. The prognosis of patients with ICC after LT were better than patients with ICC after LR in both unmatched (HR 0.65, P = 0.002) and matched cohorts (HR 0.62, P = 0.009). The 5-year OS rate after LT could be improved to 61.7% in patients with local advanced ICC after neoadjuvant chemotherapy. In conclusion, our study demonstrated that the prognosis of patients with ICC after LT was better than patients with ICC after LR, but was still worse than patients with HCC after LT. LT with neoadjuvant chemotherapy should be considered as a treatment option for patients with locally advanced ICC, but more prospective multicenter clinical trials are needed to further confirm these results.

Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.

SETß is the predominant isoform of oncoprotein SE translocation (SET) in various breast cancer cell lines. Interactome-transcriptome analysis has shown that SETß is intimately associated with cellular stress response. Among various exogenous stimuli, formaldehyde (FA) causes distinct biological effects in a dose-dependent manner. In response to FA at different concentrations, SET dynamically shuttles between the nucleus and cytoplasm, performing diverse biofunctions to restore homeostasis. At a low concentration, FA acts as an epidermal growth factor (EGF) and activates the HER2 receptor and downstream signaling pathways in HER2+ breast cancer cells, resulting in enhanced cell proliferation. Nucleocytoplasmic transport of SETß is controlled by the PI3K/PKCα/CK2α axis and depletion or blockade of the transport of SETß suppresses EGF-induced activation of AKT and ERK. SETß also inhibits not only stress-induced activation of p38 MAPK signaling pathway, but also assembly of stress granules by hindering formation of the G3BP1-RNA complex. Our findings suggest that SET functions as an important regulator which modulates cellular stress signaling pathways dynamically.

Cementless Porous-Coated Metaphyseal Sleeves Used for Bone Defects in Revision Total Knee Arthroplasty: Short- to Mid-Term Outcomes.

OBJECTIVES: While many studies have presented excellent short-term outcomes of the metaphyseal sleeves used in revision total knee arthroplasty (TKA), currently published mid-term results remain limited and some controversial issues remain unresolved. The purpose of this study was to investigate clinical and radiographic mid-term outcomes of the sleeves for the management of metaphyseal bone defects in revision TKAs. METHODS: From 2015 to 2019, 44 patients (45 knees) who were operated with cementless porous-coated metaphyseal sleeve in revision TKA were included in this study. Bone defects were assessed according to Anderson Orthopaedic Research Institute Classification. On the tibial side, there were 37 type II and six type III, and with regards to the femur, 15 were type II, and four were type III. Through reviewing electronic records, data were collected, including baseline demographics, operative details, information of prothesis, and complications. Clinical and radiographic evaluations were performed, including Knee Society Scores (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM), the radiolucent line, level of joint line, and implant survival rate. Statistical analysis was performed by paired t-test for clinical and radiographic indexes. RESULTS: The mean follow-up time was 4.4 ± 1.4 years. During surgery, sleeve-related fractures were encountered in four (8.9%) knees, including incomplete tibial fracture of lateral cortex in one knee and of medial cortex in two knees, and longitudinal femoral metaphyseal fracture in one knee. Unions were achieved in all cases at the final follow-up. Significant improvements in KSS and WOMAC scores were found at the final follow-up, respectively, from 83.8 ± 29.1 to 152.9 ± 31.0 (t = -12.146, p < 0.001) and from 148.4 ± 42.3 to 88.1 ± 52.5 (t = 6.025, p < 0.001). The mean ROM improved from 88.7 ± 31.9° to 113.7 ± 13.7° (t = -5.370, p < 0.001). A 75 mm length of cementless stem was used in all patients and only one patient was identified as tibial end-of-stem pain. No sleeve-related revision occurred, and one patient was diagnosed with early postoperative infection and was treated with irrigation and debridement, polyethylene liner exchange, and appropriate antibiotic treatment. The overall implant survival was 97.8% with the endpoint reoperation and 100% with the endpoint revision. Osseointegration at the bone-sleeve interface was found in all patients and no loosening happened. Satisfactory alignment between 3° varus and 3° valgus was achieved in all but not in three patients. CONCLUSION: The use of metaphyseal sleeves in the treatment of bone defects in rTKAs can provide stable fixation and significantly improve the clinical scores at the midterm follow-up. In addition, the rare occurrence of end-of-stem pain suggests routine use of cementless stems. Although there are chances of intraoperative fractures, it has no negative effect on outcome when managed properly.

Heterologous Gene Regulation in Clostridia: Rationally Designed Gene Regulation for Industrial and Medical Applications.

Several species from the Clostridium genus show promise as industrial solvent producers and cancer therapeutic delivery vehicles. Previous development of shuttle plasmids and genome editing tools has aided the study of these species and enabled their exploitation in industrial and medical applications. Nevertheless, the precise control of gene expression is still hindered by the limited range of characterized promoters. To address this, libraries of promoters (native and synthetic), 5' UTRs, and alternative start codons were constructed. These constructs were tested in Escherichia coli K-12, Clostridium sporogenes NCIMB 10696, and Clostridium butyricum DSM 10702, using ß-glucuronidase (gusA) as a gene reporter. Promoter activity was corroborated using a second gene reporter, nitroreductase (nmeNTR) from Neisseria meningitides. A strong correlation was observed between the two reporters. In C. sporogenes and C. butyricum, respectively, changes in GusA activity between the weakest and strongest expressing levels were 129-fold and 78-fold. Similar results were obtained with the nmeNTR. Using the GusA reporter, translation initiation from six alternative (non-AUG) start codons was measured in E. coli, C. sporogenes, and C. butyricum. Clearly, species-specific differences between clostridia and E. coli in translation initiation were observed, and the performance of the start codons was influenced by the upstream 5' UTR sequence. These results highlight a new opportunity for gene control in recombinant clostridia. To demonstrate the value of these results, expression of the sacB gene from Bacillus subtilis was optimized for use as a novel negative selection marker in C. butyricum. In summary, these results indicate improvements in the understanding of heterologous gene regulation in Clostridium species and E. coli cloning strains. This new knowledge can be utilized for rationally designed gene regulation in Clostridium-mediated industrial and medical applications, as well as fundamental research into the biology of Clostridium species.

Comparison of Preoperative Computed Tomography and Intraoperative Estimation in Predicting the Version of a Single-Wedge Femoral Stem.

OBJECTIVE: Early prediction of stem version aids in optimization of combined version during total hip arthroplasty (THA). This study aimed to analyze the discrepancy between stem version and native femoral version measured by different methods, and to explore which method can better predict the stem version. METHODS: We retrospectively reviewed 26 patients (39 hips) treated with robot-assisted THA in our hospital between September 2019 and December 2019. A straight, single-wedge, cementless stem (Accolade II) was used in all cases. Preoperative femoral version was measured at three levels on computerized tomography (CT) scan from the top to the middle level of femoral neck (Level 1 to Level 3). During THA, the version on cutting surface was measured prior to femoral broaching based on two reference lines: mid-cortical line and T line (trochanteric fossa to the middle of medial cortex). After femoral broaching, stem version was measured based on the femoral neck trial using Mako system (Stryker). In the statistical analysis, the difference and absolute discrepancy between stem version and femoral version measured with various methods were examined using paired t-test, and the relationship between stem version and various femoral versions were examined using correlation analysis. RESULTS: Mean femoral neck version (Level 1) was 9.5° ± 2.6° (range, -16.8°-42.5°), while mean stem version measured by Mako system was 19.9° ± 2.0° (range, -8.0°-49.0°). Femoral version measured with each method showed a moderate correlation with stem version (p < 0.05). There was a significant difference between stem version and femoral version except at Level 3, with a mean difference of 0.8° ± 13.6° (p = 0.729). With regard to the intraoperative estimation, stem version significantly increased compared to the value based on mid-cortical line, with a mean difference of 8.4° ± 13.1° (p < 0.001). However, the mean value of stem version was a little smaller than that of femoral version measured by reference to T line, but without statistical significance (p = 0.156). No postoperative dislocations occurred during the study period. No revision was required for any component. CONCLUSIONS: The middle level of femoral neck on CT scan and T line on cutting surface are better references to measure femoral version for predicting postoperative stem version. However, the relationship between stem version and predictive value was flexible. Therefore, further three-dimensional studies of postoperative CT are needed to validate the press-fit fixation and rotational freedom of the single-wedge stem.

The application of custom-made 3D-printed titanium augments designed through surgical simulation for severe bone defects in complex revision total hip arthroplasty.

BACKGROUND: With the development of radiology and three-dimensional (3D) printing technology, custom-made 3D-printed titanium augments have been more widely used. However, the radiological and clinical outcomes of custom-made augments lack reports. To better understand the clinical effect of using 3D-printed titanium augments and the significance of accurate placement, the aim of this study was to assess the outcomes when using custom-made 3D-printed titanium augments and to validate the idea that surgical simulation should be done before designing custom-made augments. METHODS: A retrospective review was conducted on 31 surgical simulations and revision total hip arthroplasties using custom-made 3D-printed titanium augments. The safe zone, cup position, and hip rotation center were measured on anteroposterior radiographs. Clinical outcomes were assessed with a mean 21.1 months of follow-up. RESULTS: All patients were positioned within the safe zone, and none of the acetabular cups nor the custom-made augments had any evidence of migration at the latest follow-up. A strong correlation was found between the planned cup position and the postoperative position. The average vertical position of the center of rotation was significantly increased from 3.55 cm to 2.35 cm. The mean Harris Hip Score was increased from 40.81 preoperatively to 65.46 postoperatively. Complications included gait abnormality, groin pain, fracture of the greater trochanter, and partial palsy of the sciatic nerve. However, patient satisfaction reached 92.3%. CONCLUSION: Surgical simulations help to design custom-made augments accurately and improve surgical plans. Acetabular components supported with custom-made 3D-printed augments is a useful method to bridge severe bone deficiencies. In this study, both the radiologic results and clinical outcomes were favorable. LEVEL OF EVIDENCE: Level 4.

The optimal screw-hole positions of the eccentric revision cup based on a morphological study.

BACKGROUND: Bridging bone defects in revision total hip arthroplasty is a challenge to orthopedic surgeons. The eccentric revision cup is a progression of jumbo cup. Our aim is to confirm the optimal screw-hole positions of the eccentric revision cup by morphological measurements of three-dimensional pelvic reconstruction. METHODS: Eighty CT images were converted to virtual three-dimensional bones. After simulating the surgery procedure, all available screw holes were inserted with the screws in virtual. By measuring the length of the screw in the pelvic bone, we determined the rich bone stock area. Then the screw holes were designed according to the characteristics of bone stock distribution. The peripheral screw-hole cluster and inner screw-hole cluster were studied respectively. RESULTS: For peripheral screw-hole cluster, five screw holes were evenly distributed between point A and point B in the thicker rim. For inner screw-hole cluster, screw hole 1 and screw hole 2 are the recommended inner screw holes. CONCLUSION: The eccentric revision cup has inherited the strengths of jumbo cup besides several unique advantages, including using the peripheral screws enhancing primary stability; decreasing the shift of hip rotation center and restoring biomechanical function; reducing the risk of dislocation because of the smaller head-cup differences; increasing the contact area between the outer cup and the host bone while maintaining a normal inclination of the inner cup. In this study, we confirmed the optimal screw-hole positions of the eccentric revision cup by surgical simulation and morphological measurement. However, biomechanical tests are still being further explored.

A comparsion study between debridement, antibiotics, and implant retention and two-stage revision total knee arthroplasty for the management of periprosthetic joint infection occurring within 12 weeks from index total knee arthroplasty.

BACKGROUND: Managing periprosthetic joint infections are variable in practices. Debridement, antibiotics, and implant retention (DAIR) is one of the favorable interventions. Given that the success rate of the two-stage revision total knee arthroplasty (rTKA) might be overestimated. The purpose of this study is to compare the success rate between DAIR and standard two-stage rTKA with a comparable intervention time. METHODS: We retrospectively reviewed the consecutive knee periprosthetic joint infection cases which underwent DAIR or two-stage rTKA (all procedures were performed by the senior author) within 12 weeks since their primary TKA between July 2009 and October 2019. Average follow-up was 72.20 ± 40.70 months (range 29-148 months) in the DAIR group compared to 89.14 ± 43.06 months after spacer insertion (range 29-163 months) in the two-stage revision group (P = 0.156). According to different interventions, demographic data; timing of surgical intervention; hospital for special surgery knee score; and success rate were collected and compared between the DAIR group and two-stage revision group. Failure of treatment was based on the Delphi consensus and the fate of spacers. The pathogen types and failure cases were also recorded and analyzed. RESULTS: Average follow-up was 72.20 ± 40.70 months (range 29-148 months) in the DAIR group compared to 89.14 ± 43.06 months after spacer insertion (range 29-163 months) in the two-stage revision group. Time from index surgery was 3.90 ± 2.92 weeks (range 0-12 weeks) in the DAIR group, and 5.11 ± 2.86 weeks (range 0-12 weeks) in the 2-stage exchange group, respectively. The success rate was 70.0% and 75.0% in the DAIR group and two-stage revision group, respectively. But no significant differences were observed between the two groups. CONCLUSION: DAIR demonstrated comparable effectiveness with two-stage rTKA. We recommended DAIR as a choice for patients with current infection within 12 weeks after primary TKA. For methicillin-resistant staphylococcal infections and fungal infections, two-stage rTKA might be preferred.

Adhesive anastomosis for organ transplantation.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.

[Value of personalized extramedullary positioning technique on tibia side for coronal alignment of tibial prosthesis in total knee arthroplasty].

OBJECTIVE: To explore the coronal alignment of tibial prosthesis after osteotomy using personalized extramedullary positioning technique on tibia side in total knee arthroplasty (TKA). METHODS: A clinical data of 170 patients (210 knees) who underwent primary TKA between January 2020 and June 2021 and met the selection criteria was retrospectively analyzed. Personalized and traditional extramedullary positioning techniques were used in 93 cases (114 knees, personalized positioning group) and 77 cases (96 knees, traditional positioning group), respectively. The personalized extramedullary positioning was based on the anatomical characteristics of the tibia, a personalized positioning point was selected as the proximal extramedullary positioning point on the articular surface of the tibial plateau. There was no significant difference between the two groups in gender, age, body mass index, surgical side, course of osteoarthritis, and Kellgren-Lawrence classification ( P>0.05). The preoperative tibial bowing angle (TBA) formed by the proximal and distal tibial coronal anatomical axes in the personalized positioning group was measured and the tibia axis was classified, and the distribution of personalized positioning point was analyzed. The pre- and post-operative hip-knee-ankle angle (HKA), the lateral distal tibial angle (LDTA), and the postoperative tibia component angle (TCA), the excellent rate of tibial prosthesis alignment in coronal position were compared between the two groups. RESULTS: In the personalized positioning group, 58 knees (50.88%) were straight tibia, 35 knees (30.70%) were medial bowing tibia, and 21 knees (18.42%) were lateral bowing tibia. The most positioning points located on the highest point of the lateral intercondylar spine (62.07%) in the straight tibia group, while in the medial bowing tibia and lateral bowing tibia groups, most positioning points located in the area between the medial and lateral intercondylar spines (51.43%) and the lateral slope of the lateral intercondylar spine (57.14%), respectively. The difference in HKA between pre- and post-operation in the two groups was significant ( P<0.05); while the difference in LDTA was not significant ( P>0.05). There was no significant difference in preoperative LDTA and HKA and the difference between pre- and post-operation between groups ( P>0.05). But there was significant difference in postoperative TCA between groups ( P<0.05). The postoperative tibial plateau prosthesis in the traditional positioning group was more prone to varus than the personalized positioning group. The excellent rates of tibial prosthesis alignment in coronal position were 96.5% (110/114) and 87.5% (84/96) in personalized positioning group and traditional positioning group, respectively, showing a significant difference between groups ( χ 2=7.652, P=0.006). CONCLUSION: It is feasible to use personalized extramedullary positioning technique for coronal osteotomy on the tibia side in TKA. Compared with the traditional extramedullary positioning technique, the personalized extramedullary positioning technique has a higher excellent rate of tibial prosthesis alignment in coronal position.

Bisphenol F suppresses insulin-stimulated glucose metabolism in adipocytes by inhibiting IRS-1/PI3K/AKT pathway.

Obesity is one of the risk factors of metabolic diseases. Decreased sensitivity to insulin or impairment of the insulin signaling pathway may affect the metabolism of adipose tissue. Bisphenol F (BPF) has been widely used in various products as a substitute for bisphenol A (BPA). BPA has been defined as "obesogen". However, knowledge about the correlation between BPF and obesity is very limited. This study was aimed to explore the effects of BPF on glucose metabolism and insulin sensitivity in mammalian tissues, using a mouse 3T3-L1 adipocyte line as the model. Differentiated 3T3-L1 adipocytes were treated with BPF at various concentrations for 24 h or 48 h, followed by the measurement of cell viability, lipid accumulation, expression levels of adipocytokines, glucose consumption, and impairment of the insulin signaling pathway. The results indicated that BPF had no effect on the size of 3T3-L1 adipocytes, but the expression of leptin, adiponectin and apelin was decreased, while that of chemerin and resistin was increased after 48 h of BPF treatment. Moreover, BPF inhibited the glucose consumption, the expression of GLUT4, and its translocation to the plasma membranes in 3T3-L1 adipocytes. Western blot analysis indicated that the activation of IRS-1/PI3K/AKT signaling pathway was inhibited by BPF, which resulted in reduced GLUT4 translocation. In conclusion, our data suggest that exposure of adipocytes to BPF may alter the expression of calorie metabolism-related adipokines and suppress insulin-stimulated glucose metabolism by impairing the insulin signaling (IRS-1/PI3K/AKT) pathway.

Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients.

Background and Aims: Intrahepatic cholangiocarcinoma has an increasing global incidence and mortality rate. Hepatectomy is still the most effective curative treatment for patients with ICC, but the prognosis of patients with ICC is still poor even after curative resection. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival of patients with ICC after hepatectomy. Methods: We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in ICC patients. The nomogram was validated by C-index, ROC curve and calibration curves. Results: A total of 919 patients with ICC after hepatectomy between 2000 and 2018 were included in this study. A nomogram based on six independent prognostic factors (Black race, AJCC T, AJCC N, AJCC M, chemotherapy and PLNR ≥ 0.15) was developed for the prediction of CSS at 3 and 5 years. The C-index of the nomogram and AJCC stage system were 0.709 and 0.657 in the training cohort respectively. The 3- and 5-year AUCs of nomogram were 0.744 and 0.75 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. Conclusions: In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in ICC patients after hepatectomy. We have confirmed the precise calibration and acceptable discrimination power of our nomogram. The predictive power of this nomogram may be improved by considering other potential important factors and also by external validation.