Development and application of sugarcane streak mosaic virus vectors.

Sugarcane streak mosaic virus (SCSMV) is one of the major pathogens of sugarcane in the world. Molecular studies and disease management of SCSMV are hindered by the lack of efficient infectious clones. In this study, we successfully constructed Agrobacterium infiltration based infectious clone of SCSMV with different variants. Infectious clones of wild type SCSMV could efficiently infect Nicotiana benthamiana and sugarcane plants resulting in streak and mosaic symptoms on systemic leaves which were further confirmed with RT-PCR and serological assays. SCSMV variants of less adenylation displayed attenuated pathogenicity on N.benthamiana. SCSMV-based recombinant heterologous EGFP protein vector was also developed. The EGFP-tagged recombinant SCSMV could highly expressed in vegetative organs including roots. These infectious clones of SCSMV could be further developed for platform tools for both biotechnological studies and management of SCSMV disease.

Safety and Efficacy of Stent-Graft in the Treatment of Aortoiliac Artery Occlusive Disease: A Multicenter Study of Short-Term and Medium-Term Outcomes.

BACKGROUND: To evaluate the short-term and mid-term safety and efficacy of stent-graft compared with bare stents for treatment of aortoiliac occlusive disease (AIOD). METHODS: One hundred eighty three patients diagnosed with AIOD who received stent implantation at 3 vascular centers in north China between January 2019 and December 2021 were enrolled. Patients were divided into those undergoing stent-graft (Group A; n = 67) or bare stent (Group B; n = 116) implantation for retrospective cohort analysis. Efficacy was assessed as surgical success rate and rate of freedom from clinically driven target lesion reintervention at each follow-up time point. Safety was assessed by the rate of perioperative complication, major limb amputation, and aortoiliac artery-related mortality. RESULTS: There were no preoperative baseline differences between the 2 groups (P > 0.05). The surgical success was 91.04% for Group A, significantly higher than that for Group B (79.31%; P < 0.05). Incidence of perioperative complications was 2.98% for Group A, significantly lower than that for Group B (9.48%, P < 0.05), as was the rate of major limb amputation (A: 1.49% vs. B: 5.17%) and aortoiliac artery-related mortality (A: 1.49% vs. B: 4.31%), although these 2 indicators were not significantly different (P > 0.05). Follow-up rates were 91.8% for the total follow-up time of 3 years. Kaplan-Meier survival curve analysis gave significantly higher 1-year and 2-year freedom from clinically driven target lesion reintervention for Group A (98.51% and 95.52%) than for Group B (95.69% and 89.66%, P < 0.05). CONCLUSIONS: Stent-graft is more effective and safer than bare stent in the treatment of AIOD.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform.

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. STATEMENT OF SIGNIFICANCE: Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

An Interspecies Recombinant Sida Yellow Mosaic China Virus Isolate and Betasatellite Cause a Leaf Curl Disease in Tobacco in Hainan, China.

Tobacco (Nicotiana tabacum) is an herbaceous crop. Cigar tobacco, a group of tobacco cultivars, has recently been planted in a few provinces in China. Since its introduction, symptoms such as leaf curling and vein thickening have appeared. Here we report a begomovirus, Sida yellow mosaic China virus-Hainan isolate (designated SiYMCNV-HN), associated with the betasatellite (designated SiYMCNB-HN) as the causal agent of a leaf curl disease in cigar tobacco (N. tabacum cv. Haiyan101) in Hainan Province, China. Phylogenetic and recombination analyses indicate that SiYMCNV-HN is an interspecies recombinant with a SiYMCNV isolate as the major parent and a Sida yellow vein Vietnam virus isolate as the minor parent. Full-length infectious clones of SiYMCNV-HN and SiYMCNB-HN were generated, which were highly infectious and induced high pathogenicity through agroinfiltration in Nicotiana benthamiana and N. tabacum. This newly reported recombinant begomovirus poses potential threats to tobacco plantations in the region.

Ingenious Synergy of a Pathology-Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis.

Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M-M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M-M@I nanoparticles are taken up well by lipopolysaccharide-induced RAW 264.7 macrophages or bone marrow-derived macrophages (BMDMs). In vitro, the M-M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast-related enzymes. They also reduce the polarization of macrophages to a pro-inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen-induced arthritis, the M-M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology-specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

Perioperative safety and efficacy of robot-assisted total hip arthroplasty in ERAS-managed patients: a pilot study.

AIMS: Robot-assisted total hip arthroplasty (rTHA) boasts superior accuracy in implant placement, but there is a lack of effective assessment in perioperative management in the context of enhanced recovery after surgery (ERAS). This study aimed to compare the effectiveness and safety of rTHA versus conventional total hip arthroplasty (cTHA) in ERAS-managed patients. METHODS: In this prospective trial, a total of 60 eligible patients aged between 18 and 80 years were randomly divided into two groups to undergo either rTHA or cTHA. The primary outcomes included blood loss parameters. Secondary outcomes were the duration of the operation, surgical time, WOMAC pain score, WOMAC stiffness score, WOMAC physical function score, Harris score, and postoperative complications. RESULTS: The study cohort analyzed 59 eligible participants, 30 of whom underwent rTHA and 29 of whom underwent cTHA. Analysis could not be conducted for one patient due to severe anemia. Notably, the cTHA group had a significantly shorter surgical time than the rTHA group (69.49 ± 18.97 vs. 104.20 ± 19.63 min, P < 0.001). No significant differences were observed between the rTHA and cTHA groups for blood loss parameters, including total blood loss (1280.30 ± 404.01 vs. 1094.86 ± 494.39 ml, P = 0.137) and drainage volume (154.35 ± 121.50 vs. 159.13 ± 135.04 ml, P = 0.900), as well as intraoperative blood loss (126.67 ± 38.80 vs. 118.52 ± 60.68 ml, P = 0.544) and hidden blood loss (982.43 ± 438.83 vs. 784.00 ± 580.96 ml, P = 0.206). Only one patient in the cTHA group required allogeneic blood transfusion. At 3 months postoperatively, both groups showed improvements in WOMAC pain score, WOMAC stiffness score, WOMAC physical function score, and Harris score, with no significant differences found between the two groups. Few complications were reported in both groups without significant differences. CONCLUSIONS: Despite the longer surgical time, rTHA did not negatively affect blood loss, pain, or functional recovery or lead to an increased risk of complications in ERAS-managed patients, suggesting that rTHA can be safely and effectively incorporated into an ERAS program for primary THA.

[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.

The effect of perioperative tranexamic acid (TXA) in patients with calcaneal fractures: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively blocks the lysine-binding sites of plasminogen, plasmin, and tissue plasminogen activator, delaying fibrinolysis and blood clot degradation. However, the effect of TXA on patients with calcaneal surgery remains controversial. Our objective was to evaluate the effectiveness of TXA in calcaneal fractures surgeries. METHODS: The electronic literature databases of Pubmed, Embase, and Cochrane library were searched in December 2022. The data on blood loss, the stay in the hospital, the duration of surgery, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, and wound complication were extracted. The Stata 22.0 software was used for the meta-analysis. RESULTS: Four randomized controlled studies met our inclusion criteria. This meta-analysis showed that TXA significantly reduced postoperative blood loss during the first 24 h (p < 0.001), improved the level of hemoglobin (p < 0.001) and hematocrit (p = 0.03), and reduced the risk of wound complications (p = 0.04). There was no significant difference between the two groups regarding total and intraoperative blood loss, hospital stay, duration of surgery, platelet count, activated partial thromboplastin time, and prothrombin time. CONCLUSION: TXA significantly reduced blood loss during the first 24 h postoperatively, improved the level of hemoglobin and hematocrit, and reduced the risk of wound complications. Given the evidence, TXA can be used in patients with calcaneal fractures and had the potential benefit of blood reduction. PROTOCOL REGISTRATION: The protocol was registered in PROSPERO (registration No. CRD42023391211).

Adductor Canal Block Combined with General Analgesia for Patients with Recurrent Patellar Dislocation Undergoing "3-in-1" Procedure Surgery: A Prospective Randomized Controlled Trial.

OBJECTIVE: Patellar dislocation is a common injury in sports medicine. While surgical treatment is an important option, pain is severe after surgery. This study compared the analgesic effect and early rehabilitation quality between adductor canal block combined with general analgesia (ACB + GA) and single general analgesia (SGA) after recurrent patellar dislocation (RPD) for "3-in-1" procedure surgery. METHODS: From July 2018 to January 2020, a prospective randomized controlled trial was conducted in analgesia management after RPD for "3-in-1" procedure surgery. The 40 patients in the experimental group received ACB (0.3% ropivacaine 30 mL) + GA, while the 38 patients in the control group received SGA. Patients in both groups received "3-in-1" procedure surgery, standardized anesthesia, and analgesia during hospitalization. The outcomes included the visual analog scale (VAS), quadriceps strength, Inpatient Satisfaction Questionnaire (IPSQ), Lysholm scores, and Kujala scores. Total rescue analgesic consumption and adverse events were also recorded. One-way analysis of variance (ANOVA) was used to compare continuous variables between groups and chi-square or Fisher's exact tests were used to compare count data. Nonparametric Kruskal-Wallis H tests evaluated ranked data. RESULTS: No significant differences in resting VAS scores were observed at 8, 12, and 24 h postoperatively. However, the flexion and moving VAS scores of the ACB + GA group were significantly lower than those of the SGA group (p < 0.05). Meanwhile, the first triggering of rescue analgesics was advanced in the SGA group (p < 0.0001), and the dose of opioid analgesics was significantly higher (p < 0.0001). The quadriceps strength of the ACB + GA group was higher than that of the SGA group at 8 h postoperatively. The IPSQ of the ACB + GA group was significantly higher 24 h postoperatively. We observed no significant differences in Lysholm and Kujala scores between the two groups at 3 months after surgery. CONCLUSIONS: Early analgesia management of ACB + GA showed excellent analgesia effectiveness and a positive hospitalization experience for RPD patients undergoing "3-in-1" procedure surgery. Moreover, this management was good for early rehabilitation.

Endoscopic mucosal resection using cold snare versus hot snare in treatment for 10-19 mm non-pedunculated colorectal polyps: protocol of a non-inferiority randomised controlled study.

INTRODUCTION: Cold polypectomy has the advantages of simple operation, less time-consuming and fewer complications. Guidelines have recommended cold snare polypectomy (CSP) to resect small polyps sized ≤5 mm and sessile polyps sized 6-9 mm. However, evidence is scarce regarding cold resection for non-pedunculated polyps sized ≥10 mm. Cold snare endoscopic mucosal resection (CS-EMR) combining CSP and submucosal injection was designed to improve the complete resection rate and reduce adverse events. We hypothesise that CS-EMR is non-inferior to conventional hot snare endoscopic mucosal resection (HS-EMR) in the resection of 10-19 mm non-pedunculated colorectal polyps. METHODS AND ANALYSIS: This study is a prospective, randomised, open-label, non-inferiority, single-centre trial. Outpatients scheduled to undergo a colonoscopy and present eligible polyps will be randomised to receive either CS-EMR or HS-EMR. The primary endpoint is the complete resection. Considering that HS-EMR of 10-19 mm colorectal polyps will yield a complete resection rate of at least 92% and a non-inferiority margin of -10%, a total of 232 polyps will be included (one-sided α, 2.5%; ß, 20%). The analyses are intended to evaluate first non-inferiority (lower limit 95% CI greater than -10% for group difference) and then superiority (lower limit 95% CI>0%) if non-inferiority is achieved. Secondary endpoints include en-bloc resection, the occurrence of adverse events, the use of endoscopic clips, resection time and cost. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board of the Peking Union Medical College Hospital (No. K2203). All participants in the trial will provide written informed consent. The results of this trial will be published in an open-access way. TRIAL REGISTRATION NUMBER: NCT05545787.

First report of Ludwigia yellow vein Vietnam virus causing leaf curling on tobacco plants in Hainan province, China.

Cigar tobacco (Nicotiana tabacum L.) has been recently introduced into China for various industrial applications. From March 2022, certain symptoms of begomovirus infection, including leaf curling and thickening of veins, were sporadically (disease incidence was approximately 0.2%) observed in several cigar tobacco plantations in numerous counties in Hainan Province, China (Figure 1A). These typical symptoms of begomovirus infection were similar to those caused by the sida leaf curl virus-Hainan (SiLCV-HN) begomovirus and its associated betasatellite, as reported in our previous study on cigar tobacco plants in the same region (Wang et al. 2022). In order to determine whether these symptoms were caused by SiLCV-HN or other begomoviruses, samples of leaves were collected from the diseased tobacco plants for DNA extraction, and the total DNA was extracted for viral metagenomics using an Illumina Sequencing platform at Tiangen Biotech, Beijing. A total of 65711396 filtered reads were obtained, of which 65362322 (99.47%) reads matched to the genome of tobacco. The remaining unmapped 349074 (0.53%) reads were analyzed by BLASTn against the virus Refseq Database of GenBank and subsequently assembled. A total of 8 (5+2+1) enriched contigs of the complete sequence of ludwigia yellow vein Vietnam virus (LuYVVNV) and 9 (8+1) contigs of ludwigia yellow vein virus-associated DNA beta (LuYVB) were finally obtained (Table 1). LuYVVNV belongs to the Begomovirus genus that infects various weeds, including Ludwigia octovalvis and Impatiens balsamina. As far as we know, it was reported earliest on weed in Vietnam (Ha et al. 2008). GenBank contains data pertaining to previously identified isolates of LuYVVNV, and the data revealed that the virus was discovered in Vietnam and the Yunnan province of China currently. However, there are no reports on the infection of crops by LuYVVNV to date. The findings of the present study indicated that LuYVVNV and LuYVB could be responsible for the aforementioned symptoms observed on cigar tobacco. The complete genomes of LuYVVNV and LuYVB were amplified using primer pairs designed based on sequence assembly for viral metagenomics (Table 2). Indeed, two DNA bands with length 2763 bp of LuYVVNV genome and 1348 bp of LuYVB were amplified from leaf samples of diseased tobacco (Figure 1B). The products of polymerase chain reaction (PCR) amplification were analyzed by Sanger sequencing, and the complete nucleotide sequences of LuYVVNV and its associated betasatellite were obtained. Analysis with the BLASTn tool of NCBI revealed that the genome sequence of LuYVVNV isolated from the Hainan province of China had the highest identity of 96.9% to a different isolate of LuYVVNV (GenBank accession number: MN210347.1). These two isolates belong to the same strain, according to the latest revision of Begomovirus taxonomy (Brown et al. 2015). The isolate of LuYVVNV identified in this study was designated as LuYVVNV, Hainan isolate (LuYVVNV-HN, GenBank accession number: OP948731). BLASTn analysis further revealed that the associated betasatellite had the highest sequence identity of 96.9% with an LuYVB (GenBank accession number: AJ965541.1) of a different viral isolate, according to the classification and nomenclature of DNA betasatellites of begomoviruses (Briddon et al. 2008). The sequence of LuYVB obtained herein was therefore designated as LuYVB, Hainan isolate (LuYVB-HN, GenBank accession number: OP948732). The pathogenicity of LuYVVNV-HN and LuYVB-HN was determined using infectious clones that were constructed by ligating two fragments of LuYVVNV-HN or LuYVB-HN to a binary pCAMBIA1300 expression vector, as previously described (Wang et al. 2019). Infectious clones of LuYVVNV-HN, LuYVB-HN, and LuYVVNV-HN plus LuYVB-HN were separately agroinfiltrated into N. benthamiana for determining viral pathogenicity. The typical symptoms of begomovirus infection were observed in N. benthamiana plants inoculated with LuYVVNV-HN alone or LuYVVNV-HN plus LuYVB-HN, and the emerging leaves were mildly or severely down-curled, respectively, at 7 days post inoculation (dpi), with 100% disease incidence (6/6) (Figure 1C). Positive PCR products of the AV1 gene of LuYVVNV-HN were obtained from N. benthamiana plants inoculated with LuYVVNV-HN alone or LuYVVNV-HN plus LuYVB-HN. The ßC1 gene of LuYVB-HN was only obtained from N. benthamiana plants co-infected with LuYVVNV-HN and LuYVB-HN (Figure 1D). No symptoms of viral infection were observed in plants individually inoculated with LuYVB-HN, and the results of PCR were negative (Figure 1C and 1D). These findings indicated that the N. benthamiana plants had been successfully inoculated with LuYVVNV-HN, and that LuYVB-HN was incapable of causing infections on its own, but functioned as a helper and enhanced viral pathogenicity. This report is the first to identify isolates of LuYVVNV and LuYVB from cigar tobacco, which is an economically important crop plant. The findings provide insights into the epidemic threat of begomovirus reservoirs in weeds to crop plants, and emphasize the need for monitoring and controlling whitefly-transmitted viral diseases in tobacco plantations worldwide (Ye et al. 2021).

Staged replacement of both hips and both knees in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergoing bilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA) are an uncommon population, and their outcomes are also difficult to predict. The purpose of this study was to evaluate whether both bilateral cementless THA and cemented posterior-stabilized TKA (PS-TKA) can provide reliable outcomes for RA patients. METHODS: We retrospectively reviewed 30 RA patients (60 hips and 60 knees) who underwent both elective bilateral cementless THA and cemented PS-TKA, with a minimum follow-up of 2 years. Clinical, patient-reported, and radiographic data were retrospectively analyzed. RESULTS: The mean follow-up was 84 months (range, 24-156). By the last follow-up, the post-operative range of motion, Harris Hip Score, Knee Society Score (KSS) clinical, KSS functional, Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) hip, and WOMAC knee scores were significantly improved compared to the preoperative values. All patients achieved the ability to walk. In addition, overall satisfaction scores on a 100-point scale were 92.5 after THA and 89.6 after TKA. Only one patient underwent revision surgery due to knee joint instability, and all replaced hips and knees were radiographically stable by the assessment of the radiolucent line. The proportion of implants that did not suffer loosening or require revision surgery was 99.2% during the 84-month follow-up, based on Kaplan-Meier analysis. CONCLUSIONS: Our study suggests that bilateral cementless THA and cemented PS-TKA provides reliable mid-long-term clinical, patient-reported, and radiographic outcomes in RA patients, with high survivorship and patient satisfaction.

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.

Synergistic Effect of a Prolonged Combination Course of Tranexamic Acid and Dexamethasone Involving High Initial Doses in Total Knee Arthroplasty: A Randomized Controlled Trial.

The optimal regimes of tranexamic acid (TXA) and dexamethasone (DXM) in total knee arthroplasty (TKA) are still uncertain. The aim of this study was to assess the efficacy and safety of a prolonged course of intravenous TXA and DXM involving a high initial dose in TKA. Patients who underwent primary TKA at our center were randomized to receive one of four regimes: control (group A), prolonged course of TXA (B), prolonged course of DXM (C), or the combination of a prolonged course of TXA and DXM (D). The four groups were compared in primary outcomes (fibrinolytic and inflammatory markers, knee function, postoperative pain levels, and consumption of opioids) and secondary outcomes (blood loss, maximal drop in hemoglobin, coagulation, fasting blood glucose, and complications). A total of 162 patients were enrolled. On postoperative days 2 and 3, fibrinolytic markers were lower in groups B and D than in groups A and C; inflammatory markers were lower in groups C and D than in groups A and B. Inflammatory markers were lower in group B than in group A on postoperative day 3. Postoperative pain levels and oxycodone consumption were lower, and knee function was better in groups C and D. The four groups did not differ in any of the secondary outcomes. A prolonged course of intravenous TXA and DXM involving high initial doses can effectively inhibit postoperative fibrinolytic and inflammatory responses, reduce pain, and improve knee function after TKA.

A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma.

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.

IPACK (Interspace between the Popliteal Artery and the Capsule of the Posterior Knee) Block Combined with SACB (Single Adductor Canal Block) Versus SACB for Analgesia after Total Knee Arthroplasty.

OBJECTIVES: To evaluate the combination of the infiltration between the popliteal artery and the posterior capsule of the knee (iPACK) block and single adductor canal block (SACB) versus SACB for motor-sparing knee analgesia effects after total knee arthroplasty (TKA). METHODS: PubMed, Ovid, Cochrane Library, and other databases were searched from the inception to January 2021. Randomized controlled trials (RCTs) comparing patients receiving iPACK plus SACB with patients receiving SACB after TKA were included. The included studies were assessed by two reviewers according to the Cochrane risk of bias criteria. Meta-analysis was performed with STATA 13.0 software, the risk ratios (RR) and mean differences (MD) were used to compare dichotomous and continuous variables. The primary outcome was ambulation pain and secondary outcomes were rest pain, opioid consumption, function ability, clinical outcomes, and complications. RESULTS: Seven RCTs (304 knees in iPACK + SACB group; 305 knees in SACB group) were included. The follow-up periods ranged from 2 days to 3 months. Pooled data indicated lower pain scores at ambulation (p < 0.0001) for iPACK + SACB. When comparing the pain scores of subgroups analyzed at specific periods, lower scores in subgroups within 12 h (at rest and ambulation) and after 48 h (at ambulation) were observed in the iPACK + SACB group. Analysis demonstrated greater reduction in morphine consumption (p = 0.007) in the iPACK + SACB group. The iPACK + SACB group is also superior to the SACB group regarding function ability, which included range of motion (ROM) (p = 0.001), time up to go (TUG) test (p = 0.030), and ambulation distance (p < 0.0001). No difference was found in clinical outcomes or complications. CONCLUSIONS: With the iPACK added to SACB, pain scores, morphine consumption, functional ability were improved. Additional high-quality studies are required to further address this topic.

Mepivacaine Versus Bupivacaine in Adult Surgical Patients: A Meta-analysis, Trial Sequential Analysis of Randomized Controlled Trials.

PURPOSE: Evidence supporting the choice between mepivacaine and bupivacaine is inconclusive. This meta-analysis aims to determine whether mepivacaine can reach a similar effect to bupivacaine after surgeries. DESIGN: A meta-analysis, trial sequential analysis of randomized controlled trials (RCTs). METHODS: RCTs were identified in PubMed, EMBASE (Ovid), Medline (Ovid), and Cochrane Library using a controlled vocabulary (MeSH) and keywords. There were no date and language restrictions. We strictly included RCTs comparing mepivacaine with bupivacaine. The primary outcome was motor function recovery time. Secondary outcomes included postoperative analgesic requirement, transient neurologic symptoms (TNS), pain score at 24 hours, length of stay (LOS), duration of analgesia, complications, and patient satisfaction. A trial sequential analysis (TSA) was performed for motor function recovery time, postoperative analgesic requirement, and TNS. FINDINGS: Seven RCTs with a total of 672 patients were included. Return of motor function was quicker in patients who received mepivacaine than in those who received bupivacaine (weighted mean differences [WMD] = -2.23 minutes; 95% confidence intervals [CI], -3.58 to -0.88; P = .02; I2 = 97.08%; TSA adjusted CI -17.52 to -10.9). Postoperative analgesic requirement was significantly more with mepivacaine (risk ratio [RR] = 3.23; 95% CI, 1.37-7.62; P = .01; I2 = 55.11%; TSA adjusted CI 5.73-63.27). Duration of analgesia (WMD = -8.83 hours; 95% CI, -11.75 to -7.90; P < .001; I2 = 0%) and LOS (WMD = -3.95 hours; 95% CI, -4.83 to -3.07; P < .001; I2 = 0%) in group mepivacaine was significantly shorter compared with bupivacaine. There were no differences for TNS (RR = 3.90; 95% CI, 0.94-16.22; P = .062; I2 = 72.23%), postoperative pain score (standard mean differences [SMD] = 0; 95% CI, -0.10 to 0.10; P = .972; I2 = 0%), complications (RR = 1; 95% CI, 0.70-1.43; P = .998; I2 = 0%), and satisfaction (RR = 0.97; 95% CI, 0.85-1.11; P = .40; I2 = 45%) between bupivacaine and mepivacaine. CONCLUSIONS: Mepivacaine appears to yield a faster return of motor function and shorter LOS compared with bupivacaine. and may be more popular in short-stay and outpatient surgery. However, the results of TSA indicate that more high-quality trials are needed to confirm the true effects.

A new cocktail formula with diprospan of local infiltration analgesia in primary total hip arthroplasty: A prospective, randomized, controlled, observer-blinded study.

OBJECTIVE: This study aimed to observe the analgesic effect of the cocktail formulation with diprospan during total hip arthroplasty (THA). METHODS: From September 2018 to April 2019, 120 patients undergoing primary unilateral THA were included in this prospective, randomized, observer-blinded study. Patients were randomized into three groups, according to the different local infiltration analgesia (LIA) strategies: LIA with ropivacaine (the ropivacaine group, n = 40), LIA with a new cocktail containing ropivacaine, diprospan, and morphine (the cocktail group, n = 40), and the control group (n = 40). The primary outcomes included postoperative pain scores. The resting visual analogue scale (VAS) scores were measured at 2, 6, and 12 h after the surgery (a.m. and p.m.) on postoperative day (POD) 1, POD2, and the day of discharge. Movement VAS scores were assessed at 6 h, 12 h after the operation (a.m. and p.m.) on POD1, POD2, and the day of discharge. The secondary outcomes included opioid consumption, postoperative hospital stay, range of motion of the hip at discharge, patient satisfaction, and the results of the follow-up. RESULTS: After the screening, 120 patients were randomized into three groups (40 patients in each group). All of the patients completed the trial. The resting VAS scores in the ropivacaine group and cocktail group at 2 h were lower than those in the control group (P < 0.001 and P < 0.001, respectively, F = 17.054), and the same trend was also postoperatively found at 6 h (p = 0.005 and P = 0.002, F = 6.212). Twelve hours after the operation, the pain score in the cocktail group was lower than that in the other two groups, but only the difference between the cocktail group and the control group was statistically significant (P = 0.018, F = 3.144). From the morning of the first postoperative day to the a.m. on POD 2, the VAS scores in the cocktail group were significantly lower than those in the ropivacaine group and the control group. Furthermore, the movement VAS scores in the ropivacaine group and the cocktail group were better than those in the control group at 6 and 12 h post-operation (P < 0.05). The per capita opioid consumption in the cocktail group was less than that in the ropivacaine group and the control group within 24 h post-operation. There were no significant differences in the comparison of additional indicators among the three groups. CONCLUSION: The new cocktail with diprospan had a better result and longer duration time for early postoperative pain control in primary THA via the posterolateral approach under general anesthesia, especially for treating resting pain.

Multifunctional Yolk-Shell Structured Magnetic Mesoporous Polydopamine/Carbon Microspheres for Photothermal Therapy and Heterogenous Catalysis.

Yolk-shell structure with magnetic core, interior void and mesoporous polymer/carbon shell demonstrate potential applications in biocatalysis, magnetic biological separation, biomedicine, and magnetic resonance imaging due to their comprehensive benefits of magnetic and mesoporous shells. Herein, yolk-shell structured magnetic mesoporous polydopamine microspheres (Fe3O4@Void@mPDA) and the corresponding derivatives of carbon-based microspheres (Fe3O4@Void@mCN) are successfully fabricated through an interface assembly and selective etching approach. The obtained monodisperse Fe3O4@Void@mPDA microspheres consist of a magnetic core, a mesoporous polydopamine shell, and the large void formed between them, with perpendicular mesopores (5.2 nm), high surface area (303.3 m2g-1), and richness of functional groups. The Fe3O4@Void@mPDA microspheres show a remarkable inhibitory effect on tumor cells. Moreover, the Fe3O4@Void@mCN microspheres can immobilize ultrafine Au nanoparticles for hydrogenation of 4-nitrophenol with superb catalytic activity and excellent magnetic reusability.