Synergistic Activation of Electric Furnace Ferronickel Slag by Mechanical Grinding and Chemical Activators to Prepare Cementitious Composites.

The use of electric furnace ferronickel slag (FNS) as a supplementary cementitious material is the current focus of research. This study investigates the effect of mechanical grinding and chemical additives on the activity excition of FNS, as well as the associated synergistic mechanisms. This study shows that the addition of triethanolamine (TEA) increases the fine-grained content in FNS powder, which facilitates the depolymerization of FNS and the early hydration of aluminum tricalcium. Furthermore, the addition of Ca(OH)2 raises the alkalinity of the cementitious system, which promotes the availability of Ca2+ ions and accelerates the hydration process, resulting in the generation of additional hydration products. The enhancement of late hydration of C3S by TEA and its combination with the secondary hydration of Ca2+ at high alkalinity are the pivotal factors to improve the strength of cementitious composite. A mixture of FNS and 0.03% TEA is subjected to grinding for 90 min, using the obtained micropowder which replaces 20% of the cement, and subsequently, after being excited with 3% Ca(OH)2, the FNS micropowder reaches the quality standards of S95 slag powder. It is worth remarking that the micropowder prepared by mixing FNS with 3% Ca(OH)2 and 0.03% TEA and grinding it for 81 min also meets the S95 standard for slag powder. The larger dosage of FNS in cement is supported by the observed synergy between TEA and Ca(OH)2. This research will provide valuable insights for the expanded application of FNS in construction materials.

ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1-Directed 4-1BB Activation.

Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune-stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2″ PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when cross-linked with PD-L1-positive cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/regulatory T cells in the tumor microenvironment (TME), rendering an immunologically "cold" tumor "hot." Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well tolerated and did not induce hepatotoxicity in non-human primates. According to computational semimechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1-rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 cross-linking-dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors. SIGNIFICANCE: The tetravalent PD-L1×4-1BB bispecific antibody ATG-101 activates 4-1BB+ T cells in a PD-L1 cross-linking-dependent manner, minimizing the hepatotoxicity of existing 4-1BB agonists and suppressing growth of ICI-resistant tumors. See related commentary by Ha et al., p. 1546.

LiPF6 Induces Phosphorization of Garnet-Type Solid-State Electrolyte for Stable Lithium Metal Batteries.

Garnet solid electrolyte Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is an excellent inorganic ceramic-type solid electrolyte; however, the presence of Li2 CO3 impurities on its surface hinders Li-ion transport and increases the interface impedance. In contrast to traditional methods of mechanical polishing, acid corrosion, and high-temperature reduction for removing Li2 CO3 , herein, a straightforward "waste-to-treasure" strategy is proposed to transform Li2 CO3 into Li3 PO4 and LiF in LiPF6 solution under 60 °C. It is found that the formation of Li3 PO4 during LLZTO pretreatment facilitates rapid Li-ion transport and enhances ionic conductivity, and the LLZTO/PAN composite polymer electrolyte shows the highest Li-ion transference number of 0.63. Additionally, the dense LiF layer serves to safeguard the internal garnet solid electrolyte against solvent decomposition-induced chemical adsorption. Symmetric Li/Li cells assembled with treated LLZTO/PAN composite electrolyte exhibit a critical current density of 1.1 mA cm-2 and a long lifespan of up to 700 h at a current density of 0.2 mA cm-2 . The Li/LiFePO4 solid-state cells demonstrate stable cycling performances for 141 mAh g-1 at 0.5 C, with capacity retention of 93.6% after 190 cycles. This work presents a novel approach to converting waste into valuable resources, offering the advantages of simple processes, and minimal side reactions.

[Effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament reconstruction: a randomized controlled study].

Objective: To investigate the effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament (ACL) reconstruction. Methods: A total of 160 patients with ACL injuries who met the selection criteria and were admitted between November 2020 and August 2021 were selected and divided into 4 groups according to the random number table method (n=40). Group A began to take imrecoxib 3 days before operation (100 mg/time, 2 times/day); group B began to take imrecoxib 1 day before operation (100 mg/time, 2 times/day); group C took 200 mg of imrecoxib 2 hours before operation (5 mL of water); and group D did not take any analgesic drugs before operation. There was no significant difference in gender, age, body mass index, constituent ratio of meniscal injuries with preoperative MRI grade 3, constituent ratio of cartilage injury Outerbridge grade 3, and visual analogue scale (VAS) score at the time of injury and at rest among 4 groups (P>0.05). The operation time, hospitalization stay, constituent ratio of perioperative American Society of Anesthesiologists (ASA) grade 1, postoperative opioid dosage, and complications were recorded. The VAS scores were used to evaluate the degree of knee joint pain, including resting VAS scores before operation and at 6, 24, 48 hours, and 1, 3, 6, and 12 months after operation, and walking, knee flexion, and night VAS scores at 1, 3, 6, and 12 months after operation. The knee injury and osteoarthritis score (KOOS) was used to evaluate postoperative quality of life and knee-related symptoms of patients, mainly including pain, symptoms, daily activities, sports and entertainment functions, knee-related quality of life (QOL); and the Lysholm score was used to evaluate knee joint function. Results: All patients were followed up 1 year. There was no significant difference in operation time, hospitalization time, or constituent ratio of perioperative ASA grade 1 among 4 groups (P>0.05); the dosage of opioids in groups A-C was significantly less than that in group D (P<0.05). Except for 1 case of postoperative fever in group B, no complications such as joint infection, deep vein thrombosis of the lower extremities, or knee joint instability occurred in each group. The resting VAS scores of groups A-C at 6 and 24 hours after operation were lower than those of group D, and the score of group A at 6 hours after operation was lower than those of group C, and the differences were significant (P<0.05). At 1 month after operation, the knee flexion VAS scores of groups A-C were lower than those of group D, the walking VAS scores of groups A and B were lower than those of groups C and D, the differences were significant (P<0.05). At 1 month after operation, the KOOS pain scores in groups A-C were higher than those in group D, there was significant difference between groups A, B and group D (P<0.05); the KOOS QOL scores in groups A-C were higher than that in group D, all showing significant differences (P<0.05), but there was no significant difference between groups A-C (P>0.05). There was no significant difference in VAS scores and KOOS scores between the groups at other time points (P>0.05). And there was no significant difference in Lysholm scores between the groups at 1, 3, 6, and 12 months after operation (P>0.05). Conclusion: Compared with the traditional analgesic scheme, applying the concept of preemptive analgesia with imrecoxib to manage the perioperative pain of ACL reconstruction can effectively reduce the early postoperative pain, reduce the dosage of opioids, and promote the early recovery of limb function.

Pipkin type III femoral head fracture: which treatment strategy can be recommended?

BACKGROUND: Pipkin type III femoral head fractures are relatively rare injuries. Few studies have explored and described the treatment and outcomes of Pipkin type III femoral head fractures. The purpose of this study was to evaluate the efficacy of open reduction and internal fixation (ORIF) in treating Pipkin type III femoral head fractures. METHODS: We retrospectively reviewed 12 patients with Pipkin type III femoral head fractures who underwent ORIF from July 2010 and January 2018. The complications and reoperations were recorded. The visual analog scale (VAS) pain score, Harris hip score (HHS), Thompson-Epstein criteria, and SF-12 score [including the physical component summary (PCS) and the mental component summary (MCS)] were used for functional assessment. RESULTS: Among the 12 patients, ten were males and two were females, with a mean age of 34.2 ± 11.9 years. The median follow-up time was 6 years (range 4-8 years). Five patients (42%) developed osteonecrosis of the femoral head, and one patient (8%) developed nonunion. These six patients (50%) underwent total hip arthroplasty (THA). One patient (8%) developed heterotopic ossification and underwent ectopic bone excision; this patient also presented with post-traumatic arthritis. The mean final VAS pain score and HHS were 4.1 ± 3.1 points and 62.8 ± 24.4 points, respectively. According to the Thompson-Epstein criteria, there was one patient (8%) with excellent, four patients (33%) with good, one patient (8%) with fair, and six patients (50%) with poor outcomes. The PCS score and MCS score were 41.7 ± 34.7 points and 63.2 ± 14.5 points, respectively. CONCLUSION: Limited by the high incidence of osteonecrosis of the femoral head, it is difficult to achieve satisfactory functional outcomes when treating Pipkin type III femoral head fractures using ORIF, and a primary THA may be considered. However, for younger patients, considering the survivorship of prosthesis, ORIF may be recommended with the proviso that the patient is fully informed of the high complication rate associated with this procedure. LEVEL OF EVIDENCE: IV.

Lithium Salt Dissociation Promoted by 18-Crown-6 Ether Additive toward Dilute Electrolytes for High Performance Lithium Oxygen Batteries.

Lithium-oxygen batteries (LOBs) are well known for their high energy density. However, their reversibility and rate performance are challenged due to the sluggish oxygen reduction/evolution reactions (ORR/OER) kinetics, serious side reactions and uncontrollable Li dendrite growth. The electrolyte plays a key role in transport of Li+ and reactive oxygen species in LOBs. Here, we tailored a dilute electrolyte by screening suitable crown ether additives to promote lithium salt dissociation and Li+ solvation through electrostatic interaction. The electrolyte containing 100 mM 18-crown-6 ether (100-18C6) exhibits enhanced electrochemical stability and triggers a solution-mediated Li2 O2 growth pathway in LOBs, showing high discharge capacity of 10 828.8 mAh gcarbon -1 . Moreover, optimized electrode/electrolyte interfaces promote ORR/OER kinetics on cathode and achieve dendrite-free Li anode, which enhances the cycle life. This work casts new lights on the design of low-cost dilute electrolytes for high performance LOBs.

Is Ankle Arthrodesis With an Ilizarov External Fixator an Effective Treatment for Septic Ankle Arthritis? A Study With a Minimum of 6 Years of Follow-up.

BACKGROUND: Septic ankle arthritis is a devastating clinical problem with a high potential for permanent disability and amputation. Successful treatment of septic ankle arthritis remains a challenge for the surgeon and patient. Ankle arthrodesis combined with radical debridement may be an effective option to eradicate infection and salvage the limb. Although numerous fusion methods have been proposed, there is controversy about the most effective technique. QUESTIONS/PURPOSES: At a minimum follow-up of 6 years after ankle arthrodesis performed using an Ilizarov external fixator, we asked, (1) In what proportion of patients was bony fusion achieved? (2) What complications were observed, and what reoperations were performed in these patients? (3) How much did patient-reported outcomes improve from before surgery to the most recent follow-up in this group? METHODS: Between April 2010 to March 2015, we treated 59 patients for septic ankle arthritis. Of those, we considered patients who were at least 18 years of age with irreversible destruction of the joint as potentially eligible. During that time period, all patients met the prespecified criteria and were treated with ankle arthrodesis using an Ilizarov external fixator. Two percent (one of 59) of patients were excluded because they died in the second year after surgery for reasons unrelated to the procedure, and another 7% (four of 59) of patients were excluded because they were lost before the minimum study follow-up interval of 6 years. Finally, 92% (54 of 59) of patients were analyzed at a mean follow-up time of 9 ± 1 years. A total of 61% (33 of 54) were men, and they had a mean age of 48 ± 12 years. Forty-six percent (25 of 54) of patients were smokers, and 13% (seven of 54) of patients had Type 2 diabetes mellitus. All patients received radical debridement and primary arthrodesis with an Ilizarov external fixator, followed by antibiotic therapy. Postoperatively, patients were instructed to perform lower extremity functional exercises and external fixator care; weightbearing ambulation as tolerated was encouraged as early as possible. Fusion was assessed with a radiographic review that was performed by an individual who was not involved in the surgical care of these patients. We defined bony fusion as continuous trabeculae and complete cortical bridging in the fusion interface achieved before 9 months; delayed union was defined as fusion achieved by 9 to 12 months; and nonunion was defined as patients in whom fusion was not achieved by 12 months. Complications and reoperations were tallied through a record review that was performed by an individual who was not involved in the surgical care of these patients. We defined complications as any deviation from the expected postoperative course. We used the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, the VAS active pain score, and the SF-12 questionnaire (including the physical component summary [PCS] score and mental component summary [MCS] score) to assess patient-reported outcomes. The minimum clinically important difference (MCID) for the AOFAS score was 30 points of 100, the MCID for the VAS active pain score was 2 points of 10, and the MCID of PCS and MCS scores was 7 points and 9 points, respectively. RESULTS: Primary bony fusion was achieved in 94% (51 of 54) of patients. Delayed union was found in 2% (one of 54) of patients. Nonunion was found in 6% (three of 54); one of these patients underwent autologous bone grafting during revision, and bony fusion was ultimately achieved. Final bony fusion was achieved in 96% (52 of 54) of patients. Recurrent infection was found in 2% (one of 54). The median (range) AOFAS score improved from 28 points (8 to 59) before surgery to 80 points (52 to 86) at the most recent follow-up (median difference 52; p < 0.001). The median (range) VAS active pain score decreased from 8 points (6 to 9) before surgery to 2 points (0 to 5) at the most recent follow-up (median difference -6; p < 0.001). For the Short Form 12-item score, the median (range) PCS score improved from 0 points (0 to 30) before surgery to 70 points (40 to 95) at the most recent follow-up (median difference 70; p < 0.001), and the median (range) MCS score improved from 46 points (21 to 75) before surgery to 75 points (50 to 92) at the most recent follow-up (median difference 29; p < 0.001). CONCLUSION: Ankle arthrodesis with Ilizarov external fixation might eradicate an infection and restore foot function in patients with septic ankle arthritis. However, patients should be fully informed of the complications related to the external fixator, such as pin-tract infections, recurrent infection, and nonunion. Standardized and professional pin care is important. Additionally, because Ilizarov external fixators can be inconvenient to the patients' daily lives, future studies should explore how psychologic support affects patients who undergo ankle arthrodesis with these devices. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Development of a bispecific antibody targeting PD-L1 and TIGIT with optimal cytotoxicity.

Programmed death-ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are two potential targets for cancer immunotherapy, early clinical studies showed the combination therapy of anti-PD-L1 and anti-TIGIT had synergistic efficacy both in the terms of overall response rate (ORR) and overall survival (OS). It is rational to construct bispecific antibodies targeting PD-L1 and TIGIT, besides retaining the efficacy of the combination therapy, bispecific antibodies (BsAbs) can provide a new mechanism of action, such as bridging between tumor cells and T/NK cells. Here, we developed an IgG1-type bispecific antibody with optimal cytotoxicity. In this study, we thoroughly investigated 16 IgG-VHH formats with variable orientations and linker lengths, the results demonstrated that (G4S)2 linker not only properly separated two binding domains but also had the highest protein yield. Moreover, VHH-HC orientation perfectly maintained the binding and cytotoxicity activity of the variable domain of the heavy chain of heavy-chain-only antibody (VHH) and immunoglobulin G (IgG). Following treatment with BiPT-23, tumor growth was significantly suppressed in vivo, with more cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells infiltration, and selective depletion of Regulatory T cells (Tregs). BiPT-23 represents novel immunotherapy engineered to prevent hyperprogression of cancer with PD-1 blockade, and preferentially killed PD-L1+ tumor cells, and TIGIT+ Tregs but maintained CD11b+F4/80+ immune cells within the tumor microenvironment (TME).

[Experience of He's three-clear method by stages for herpes zoster on the head and face].

The clinical experience of He's three-clear method by stages for herpes zoster on the head and face is summarized. The strong-clear method (blood-letting therapy) combined with mild-clear method (acupuncture with filiform needle) are applied for the acute pain period and subacute pain period of herpes zoster on the head and face. For acute pain period, the bleeding volume should be large (more than 10 mL), and treatment is given once every other day; for the subacute pain period, the bleeding volume should be 5-10 mL, and treatment is given 2-3 times a week. In the chronic pain period, the fire needle of the warm-clear method combined with mild-clear method (acupuncture with filiform needle) are applied for the syndrome of qi-stagnation and blood-stasis, while the warm acupuncture of the warm-clear method combined with mild-clear method (acupuncture with filiform needle) ware applied for the syndrome of qi-deficiency yin-injury blood-stasis.

Imbalanced T-Cell Subsets May Facilitate the Occurrence of Osteonecrosis of the Femoral Head.

Background: Osteonecrosis of the femoral head (ONFH) is a complex disease resulting in degeneration of the hip joint. The pathogenesis of ONFH is largely unknown, but alterations in immunological factors have been proposed to play a role. Methods: We included 109 patients with ONFH and 109 age-, sex-, and body mass index-matched healthy controls in this study. The percentage of circulating CD3+, CD4+, and CD8+ lymphocytes among the total lymphocytes was identified by flow cytometry and compared between the cases and controls. Subgroup analysis within each etiological group and correlation analysis of T-cell subset levels with disease duration were performed. Furthermore, we compared the expression patterns of CD4, RANKL, and FoxP3 in the femoral head of healthy and glucocorticoid (GC)-treated ONFH rats. Results: The results showed that CD3+ and CD4+ T-cell counts and the CD4+/CD8+ ratio were significantly higher in patients with ONFH and that CD3+ lymphocyte levels were negatively correlated with disease duration. The CD4+ T-cell levels and CD4+/CD8+ ratios in the GC-ONFH etiological group were lower than those in the idiopathic-, traumatic-, and alcoholic-ONFH groups, while the CD8+ T-cell levels were higher. Furthermore, the CD3+, CD4+, and CD8+ T-cell counts and the CD4+/CD8+ ratio were higher in the GC-ONFH group than in the control group. Finally, we observed diminished levels of FoxP3/CD4 double-positive T regulatory cells and increased RANKL+ T-cell levels in the bone marrow of the femoral head in GC-ONFH rats. Conclusion: The imbalance of T-cell subsets might be involved in the pathophysiological process of ONFH, and diminished CD4+/FoxP3+ T regulatory cells may be associated with increased RANKL+ T cells in the bone marrow of the femoral head in GC-ONFH, which may facilitate bone resorption and collapse of the femoral head. Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100042642).

Management of Elderly Traumatic Ankle Arthritis with Ilizarov External Fixation.

OBJECTIVE: To evaluate the clinical curative effect of Ilizarov external fixation and ankle arthrodesis in the treatment of elderly traumatic ankle arthritis. METHODS: From June 2013 to August 2019, 72 patients with elderly traumatic ankle arthritis were treated with arthrodesis through Ilizarov external fixation technique in our institution. Conventional double-feet standing X-ray films were taken before and after operation. The tibiotalar angle on X-ray image was measured to evaluate the degree of talipes varus and valgus. The Foot and Ankle pain score of American Orthopaedics Foot and Ankle Society (AOFAS) and Visual Analog Scale (VAS) were compared by using paired t-test to evaluate the functional recovery. RESULTS: All of the patients acquired effective postoperative 18-49 months follow-up, with an average of 31.5 months. All patients were included in the analysis, among which 38 cases were males and 34 cases were females, with an average of 65.4 years (ranging from 60 to 74). All ankles achieved bony fusion; the clinical healing time was 12.7 weeks on average (11-18 weeks). The AOFAS score was 45.36 ± 6.43 preoperatively and 80.25 ± 9.16 at 12 months post-operation, with a statistically significant difference (p < 0.0001). The VAS score was 8.56 ± 1.85 on average preoperatively and 2.72 ± 0.83 at 12 months post-operation, with a statistically significant difference (p < 0.0001). The tibiotalar angle was 101.93° ± 4.12° preoperatively and 94.45° ± 2.37° at 12 months post-operation, with a statistically significant difference (p < 0.0001). The results of the functional evaluation indicated that 44 patients (61.1%) had excellent results, 18 (25%) had good results, and 10 (13.9%) had fair results. CONCLUSION: Our study demonstrated that it is possible to obtain satisfactory outcome with Ilizarov external fixation and ankle arthrodesis in the treatment of elderly traumatic ankle arthritis.

Epidemiology and Drug Resistance of Fracture-Related Infection of the Long Bones of the Extremities: A Retrospective Study at the Largest Trauma Center in Southwest China.

Objective: To describe the demographic characteristics, risk factors, and bacterial resistance of fracture-related infection (FRI) of the long bones of the extremities. Materials and Methods: This single-center study retrospectively evaluated patients with FRI of the long bones of the extremities at West China Hospital between January 2012 and December 2017, and analyzed the demographic characteristics, risk factors, distribution of pathogenic bacteria, and bacterial drug resistance. Results: Among 9,900 patients, 535 patients (5.4%) were diagnosed with FRI. The most common site of FRI was tibiofibular (298, 55.7%), with 424 cases (79.2%) of open fractures, and 282 cases (52.7%) due to traffic injuries. The 41-50 years age group had the highest incidence of FRI with 157 (29.3%) cases. Overall, 546 strains of 52 types of bacteria were detected in FRI patients, with 105 strains of multidrug-resistant (MDR) bacteria. Methicillin-resistant Staphylococcus aureus (48, 8.8%) and extended-spectrum-ß-lactamase Escherichia coli (32, 5.8%) accounted for the largest proportion. Multivariate logistic regression analysis showed that sex (odds ratio [OR] 1.813; 95% confidence interval [CI], 1.071∼3.070; P = 0.027) and fracture type (OR 3.128; 95% CI, 1.683∼5.815; P < 0.001) were independent risk factors for monomicrobial infection (MI). Female sex (OR 4.190; 95% CI, 1.212∼14.486; P = 0.024) was an independent risk factor for polymicrobial infection (PI). Conclusion: This study clarified the infection rates, changes in the bacterial spectrum, and drug resistance characteristics, and risk factors of FRI of the long bones of the extremities in the largest trauma center in southwest China.

Effectiveness of Ilizarov Ankle Arthrodesis in the Treatment of End-Stage Varus Ankle Osteoarthritis: A Retrospective Study.

OBJECTIVE: To evaluate the outcomes of Ilizarov ankle arthrodesis in the treatment of end-stage varus ankle osteoarthritis (OA). METHODS: This was a retrospective study of 63 patients with varus ankle OA who underwent Ilizarov ankle arthrodesis between June 2013 and December 2018. There were 24 males and 39 females with an average age of 56.57 ± 4.45 years (range, 47-64 years). Thirty-six cases were affected on the left side, and 27 were affected on the right side. The patients' mean body mass index (BMI) was 25.18 ± 2.93 kg/m2 . According to the modified Takakura staging criteria, there were 18 cases of stage 3b (28.57%) and 45 cases of stage 4 (71.43%). Nine patients were primary (14.29%), 48 were traumatic (76.19%), and six were caused by rheumatoid OA (9.52%). Functional assessments were performed according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Ankle Osteoarthritis Scale (AOS), and visual analogue scale (VAS). The tibial anterior surface angle (TAS), coronal plane tibial-talar angle (CPT), talar tilt angle (TT), deformity angle (DA), and tibial lateral surface angle (TLS) were assessed on X-ray films. RESULTS: The average operation time was 147.84 ± 13.67 min (range, 135-168 min). The average follow-up time was 34.24 ± 8.72 months (range, 24-61 months). Bony fusion was achieved in all ankles, and the fusion time was 12.43 ± 1.99 weeks on average. The average AOFAS score at the final follow-up increased from 42.14 ± 8.66 to 80.90 ± 6.80. The average VAS score and AOS pain and disability scores at the final follow-up decreased from 7.29 ± 1.27 to 2.24 ± 0.94, from 67.94 ± 7.68 to 27.92 ± 5.82, and from 71.64 ± 9.37 to 41.32 ± 8.99, respectively. The average TAS, CPT, and TLS at the final follow-up increased from 77.76° ± 4.44° to 89.81° ± 1.25°, from 69.04° ± 3.73° to 90.43° ± 1.80°, and from 82.14° ± 3.77° to 88.67° ± 2.50°, respectively. The average TT and DA at the final follow-up decreased from 8.76° ± 4.30° to 2.05° ± 1.28° and from 20.95° ± 3.73° to 1.57° ± 0.93°, respectively. Three patients developed superficial pin tract infections, all settled with local dressing and antibiotic treatment. Two patients were found to have subtalar arthritis and underwent conservative treatment. CONCLUSION: Ankle arthrodesis using the Ilizarov technique is efficient in treating end-stage varus ankle OA.

Evolution and Development of Ilizarov Technique in the Treatment of Infected Long Bone Nonunion with or without Bone Defects.

The treatment of infected bone nonunion and bone defects is a considerable challenge in the orthopedics field. The standard clinical therapy methods include local free bone transplantation, vascularized bone graft, and the Ilizarov technique; the first two are controversial due to the iatrogenic self-injury. The Ilizarov bone transport technique has been widely used to treat infected bone nonunion and bone defects, and good clinical effect has been demonstrated. Yet, it brings many related complications, which exerts additional suffering to the patient. The best treatment is to combine bone defect rehabilitation with infection control, intramedullary nail fixation, appropriate time for bone grafts, beaded type scaffold slippage and new Taylor fixation, reducing the external fixation time and the incidence of complications, thereby reducing the occurrence of patients' physical and psychological problems. This review focuses on the induction, summary and analysis of the Ilizarov bone transport technique in the treatment of infected long bone nonunion with or without bone defects, providing new ideas and methods for orthopedic disease prevention and treatment by the Ilizarov technique, which is following the development direction of digital orthopedics.

Early versus delayed hip reduction in the surgical treatment of femoral head fracture combined with posterior hip dislocation: a comparative study.

BACKGROUND: Few studies focus on the treatment of femoral head fracture combined with posterior hip dislocation, and the safe interval time between injury and hip reduction remains controversial. The purpose of this study was to evaluate and compare the outcome of early and delayed hip reduction in the surgical treatment of femoral head fracture combined with posterior hip dislocation. METHODS: A total of 71 patients were evaluated in this retrospective study. Based on the time to hip reduction, they were divided into early group (within 6 h after injury) and delayed group (between 6 and 12 h after injury). The two groups were compared in reference to hospital day, fracture healing time, the occurrence of complications and final functional outcome. The Thompson-Epstein criteria, modified Merle D'Aubigné and Postel scores, visual analog scale (VAS) and Medical Outcomes Short Form 12-item questionnaire score (SF-12) were used for final functional evaluation. RESULTS: The mean hospital stay and fracture healing time in the early group were significantly lower than those in the delayed group. The incidence of infection, post-traumatic osteoarthritis, and avascular necrosis of the femoral head (ANFH) in the delayed group were higher than that in the early group. The early group had better functional outcomes in terms of Thompson-Epstein criteria, modified Merle D'Aubigné and Postel scores and physical component scale (PCS) than the delayed group. CONCLUSIONS: For the treatment of femoral head fracture combined with posterior hip dislocation, the early and prompt hip reduction can effectively facilitate the fracture healing and patient rehabilitation, and obtain a better functional outcome.

A lingering mouthwash with sustained antibiotic release and biofilm eradication for periodontitis.

Dental plaque biofilms are believed to be one of the principal virulence factors in periodontitis resulting in tooth loss. Traditional mouthwashes are limited due to the continuous flow of saliva and poor drug penetration ability in the biofilm. Herein, we fabricated an antibiotic delivery platform based on natural polysaccharides (chitosan and cyclodextrin) as a novel mouthwash for the topical cavity delivery of minocycline. The penetration and residence mechanisms demonstrate that the platform can prolong the residence time up to 12 h on biofilms. Furthermore, sustained release can enhance the penetration of drugs into biofilms. In vitro antibiofilm experimental results indicated that the mouthwash effectively kills bacteria and eradicate biofilms. Effective treatment in vivo was confirmed by the significantly reduced dental plaque and alleviated inflammation observed in a rat periodontitis model. In summary, this novel platform can improve antibiofilm efficiency and prevent drugs from being washed away by saliva, which may provide benefits for many oral infectious diseases.

Porous copper- and lithium-doped nano-hydroxyapatite composite scaffold promotes angiogenesis and bone regeneration in the repair of glucocorticoids-induced osteonecrosis of the femoral head.

Glucocorticoids-induced osteonecrosis of the femoral head (GIONFH) is a common refractory disease. In the present study, we aimed to synthesize the nano-hydroxyapatite-copper-lithium (Cu-Li-nHA) composite porous scaffold to promote osteogenesis and angiogenesis functions to repair GIONFH by regulating the Wnt/ß-catenin and HIF-1α/VEGF pathways. The physicochemical property of the scaffold was characterized and their osteogenic and angiogenic effects were tested through a serial of experimentsin vitroandin vivo. Results showed that 0.25% Cu-Li-nHA scaffolds possessed the highest mechanical and biocompatibilityin vitro. Then the 0.25% Cu-Li-nHA scaffolds significantly enhanced the new bone formation on defects in GIONFH rabbitsin vivo. Moreover, the scaffold could increase the expression of osteogenic and angiogenic factors along with the activation of factors in Wnt/ß-catenin and HIF-1α/VEGF pathwaysin vitroandin vivo. In conclusion, the 0.25% Cu-Li-nHA scaffold could improve the osteogenesis and angiogenesis by upregulating the Wnt/ß-catenin and HIF-1α/VEGF pathways which benefited to repair the GIONFH in rabbit models.

[Moxibustion on plaque psoriasis of blood stasis: a randomized controlled trial].

OBJECTIVE: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment. METHODS: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to ashi point (target skin lesions), Zusanli (ST 36), Xuehai (SP 10) and Qihai (CV 6) for 30 min each time, 3 times a week. The control group was treated with calcipotriol ointment (0.25 g each time, once in the morning and evening) on the target skin lesions. Both groups were treated for 8 weeks. The psoriasis area and severity index (PASI) score before and after treatment, main clinical symptoms of TCM score and dermatology life quality index (DLQI) score before and after treatment and 3 and 6 moths follow-up were observed in the two groups; the clinical efficacy after treatment was evaluated and the recurrence rates of the two groups were followed up for 3 and 6 months after treatment. RESULTS: After treatment, the PASI scores in the both groups were lower than before treatment (P<0.01). After treatment and 3 and 6 months follow-up, the main clinical symptoms of TCM scores and DLQI scores of the two groups were lower than those before treatment (P<0.05), and at 3 and 6 months follow-up, those in the observation group were lower than the control group (P<0.01). There was no statistically significant difference between the observation group and the control group in overall effective rate and target skin lesion effective rate (P>0.05). At 3 and 6 months follow-up, the overall recurrence rate and target skin lesion recurrence rate in the observation group were lower than those in the control group (P<0.05). CONCLUSION: Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Positive charge in the complementarity-determining regions of synthetic nanobody prevents aggregation.

In the past, specificity and affinity were the priority for synthetic antibody library. However, therapeutic antibodies need good stability for medical use. Through carefully adjust the chemical diversity in CDRs, one hopes to design a synthetic antibody library with good developability. Here we thoroughly analyzed 296 nanobody sequences and structures, constructed a fully-functional synthetic nanobody library, evaluated the relationship between aggregation and isoelectric point, and found that high-pI nanobodies were more resistant to aggregation than low-pIs. As we used the same framework for constructing the library, CDRs charge played a crucial role in mediating nanobody aggregation. We also analyzed the theoretical pI of 296 nanobodies from PDB, about 75% had basic pI, only 25% were acidic. Those results provided useful guidelines for designing next-generation synthetic nanobody libraries and for identifying potent and safe nanobody therapeutics.

Synergistic antitumor effect of the anti-ErbB2 antibodies trastuzumab and H2-18 on trastuzumab-resistant gastric cancer cells.

Trastuzumab resistance is a severe problem in the treatment of ErbB2-amplified cancer. Although trastuzumab plus pertuzumab is able to partly overcome trastuzumab resistance in ErbB2-overexpressing cancer, its antitumor efficacy remains limited. The present study investigated the antitumor activity of the combination of trastuzumab with H2-18, which is an antibody targetinsg ErbB2 domain I. Cell proliferation and inhibition experiments indicated that H2-18 and trastuzumab synergistically inhibited the proliferation of both the trastuzumab-sensitive gastric cancer cell line, NCI-N87 and the trastuzumab-resistant gastric cancer cell line, NCI-N87-TraRT. Furthermore, H2-18 plus trastuzumab inhibited the growth of NCI-N87-TraRT cells more effectively than trastuzumab plus pertuzumab, both in vitro and in vivo. Compared with trastuzumab plus pertuzumab, H2-18 plus trastuzumab had a potent ability to inhibit NCI-N87-TraRT cells to form colonies. Notably, H2-18 plus trastuzumab was more effective in inducing cell death than trastuzumab plus pertuzumab. The in vivo studies demonstrated that H2-18 plus trastuzumab effectively inhibited the growth of both NCI-N87 and NCI-N87-TraRT xenograft tumors. Further experiments revealed that in NCI-N87-TraRT cells, H2-18 plus trastuzumab was comparable to trastuzumab plus pertuzumab in the inhibition of phosphorylated (p-)HER3, p-AKT and p-ERK. However, compared with trastuzumab plus pertuzumab, H2-18 plus trastuzumab effectively activated ROS production and the phosphorylation of JNK and c-jun in NCI-N87-TraRT cells. Therefore, the superior antitumor efficacy of H2-18 plus trastuzumab over trastuzumab plus pertuzumab may be mainly attributable to the potent cell death-inducing activity. In addition, the in vitro and in vivo antitumor effect of the combination of H2-18, trastuzumab and pertuzumab were further investigated. The results revealed that H2-18 plus trastuzumab plus pertuzumab exhibited a maximal antitumor effect among all the anti-ErbB2 monoclonal antibody combinations tested. In summary, H2-18 plus trastuzumab may have potential as an effective strategy to overcome the resistance to trastuzumab in ErbB2-amplified gastric cancer cell lines.