Tumor-derived exosomal PD-L1: a new perspective in PD-1/PD-L1 therapy for lung cancer.

Exosomes play a crucial role in facilitating intercellular communication within organisms. Emerging evidence indicates that a distinct variant of programmed cell death ligand-1 (PD-L1), found on the surface of exosomes, may be responsible for orchestrating systemic immunosuppression that counteracts the efficacy of anti-programmed death-1 (PD-1) checkpoint therapy. Specifically, the presence of PD-L1 on exosomes enables them to selectively target PD-1 on the surface of CD8+ T cells, leading to T cell apoptosis and impeding T cell activation or proliferation. This mechanism allows tumor cells to evade immune pressure during the effector stage. Furthermore, the quantification of exosomal PD-L1 has the potential to serve as an indicator of the dynamic interplay between tumors and immune cells, thereby suggesting the promising utility of exosomes as biomarkers for both cancer diagnosis and PD-1/PD-L1 inhibitor therapy. The emergence of exosomal PD-L1 inhibitors as a viable approach for anti-tumor treatment has garnered significant attention. Depleting exosomal PD-L1 may serve as an effective adjunct therapy to mitigate systemic immunosuppression. This review aims to elucidate recent insights into the role of exosomal PD-L1 in the field of immune oncology, emphasizing its potential as a diagnostic, prognostic, and therapeutic tool in lung cancer.

Validating core therapeutic targets for osteoporosis treatment based on integrating network pharmacology and informatics.

OBJECTIVE: Our goal was to find metabolism-related lncRNAs that were associated with osteoporosis (OP) and construct a model for predicting OP progression using these lncRNAs. METHODS: The GEO database was employed to obtain gene expression profiles. The WGCNA technique and differential expression analysis were used to identify hypoxia-related lncRNAs. A Lasso regression model was applied to select 25 hypoxia-related genes, from which a classification model was created. Its robust classification performance was confirmed with an area under the ROC curve close to 1, as verified on the validation set. Concurrently, we constructed a ceRNA network based on these genes to unveil potential regulatory processes. Biologically active compounds of STZYD were identified using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database. BATMAN was used to identify its targets, and we obtained OP-related genes from Malacards and DisGeNET, followed by identifying intersection genes with metabolism-related genes. A pharmacological network was then constructed based on the intersecting genes. The pharmacological network was further integrated with the ceRNA network, resulting in the creation of a comprehensive network that encompasses herb-active components, pathways, lncRNAs, miRNAs, and targets. Expression levels of hypoxia-related lncRNAs in mononuclear cells isolated from peripheral blood of OP and normal patients were subsequently validated using quantitative real-time PCR (qRT-PCR). Protein levels of RUNX2 were determined through a western blot assay. RESULTS: CBFB, GLO1, NFKB2 and PIK3CA were identified as central therapeutic targets, and ADD3-AS1, DTX2P1-UPK3BP1-PMS2P11, TTTY1B, ZNNT1 and LINC00623 were identified as core lncRNAs. CONCLUSIONS: Our work uncovers a possible therapeutic mechanism for STZYD, providing a potential therapeutic target for OP. In addition, a prediction model of metabolism-related lncRNAs of OP progression was constructed to provide a reference for the diagnosis of OP patients.

Modifying Escherichia coli to mimic Shigella for medical microbiology laboratory teaching: a new strategy to improve biosafety in class.

Introduction: Laboratory teaching of medical microbiology involves highly pathogenic microorganisms, thus posing potential biosafety risks to the students and the teacher. To address these risks, non/low-pathogenic microorganisms were modified to mimic highly pathogenic ones or highly pathogenic microorganisms were attenuated directly using the CRISPR/Cas9 technology. This study describes the modification of Escherichia coli DH5α to mimic Shigella and its evaluation as a safe alternative for medical laboratory teaching. Methods: To generate E. coli DH5α△FliC△tnaA2a, the tnaA and FliC genes in E. coli DH5α were knocked out using CRISPR/Cas9 technology; a plasmid bearing the O-antigen determinant of S. flexneri 2a was then constructed and transformed. Acid tolerance assays and guinea pig eye tests were used to assess the viability and pathogenicity, respectively. Questionnaires were used to analyze teaching effectiveness and the opinions of teachers and students. Results: The survey revealed that most teachers and students were inclined towards real-time laboratory classes than virtual classes or observation of plastic specimens. However, many students did not abide by the safety regulations, and most encountered potential biosafety hazards in the laboratory. E. coli DH5α△FliC△tnaA2a was biochemically and antigenically analogous to S. flexneri 2a and had lower resistance to acid than E. coli. There was no toxicity observed in guinea pigs. Most of teachers and students were unable to distinguish E. coli DH5α△FliC△tnaA2a from pure S. flexneri 2a in class. Students who used E. coli DH5α△FliC△tnaA2a in their practice had similar performance in simulated examinations compared to students who used real S. flexneri 2a, but significantly higher than the virtual experimental group. Discussion: This approach can be applied to other high-risk pathogenic microorganisms to reduce the potential biosafety risks in medical laboratory-based teaching and provide a new strategy for the development of experimental materials.

Exosomes and osteosarcoma drug resistance.

Osteosarcoma (OS) is a primary malignant tumor of bone characterized by the formation of bone tissue or immature bone by tumor cells. Because of its multi-drug resistance, even with the improvement of chemotherapy and the use of targeted drugs, the survival rate of osteosarcoma (OS) is still less than 60%, and it is easy to metastasize, which is a difficulty for many clinicians and researchers. In recent years, with the continuous research on exosomes, it has been found that exosomes play a role in the diagnosis, treatment and chemotherapy resistance of osteosarcoma due to their unique properties. Exosomes can reduce the intracellular accumulation of chemotherapeutic drugs by mediating drug efflux, thus inducing chemotherapeutic resistance in OS cells. Exosomal goods (including miRNA and functional proteins) carried by exosomes also show great potential in affecting the drug resistance of OS. In addition, miRNA carried by exosomes and exosomes exist widely in tumor cells and can reflect the characteristics of parent cells, so it can also be used as a biomarker of OS. At the same time, the development of nanomedicine has given a new hope for the treatment of OS. Exosomes are regarded as good natural nano-carriers by researchers because of their excellent targeted transport capacity and low toxicity, which will play an important role in the field of OS therapy in the future. This paper reviews the internal relationship between exosomes and OS chemotherapy resistance, discusses the broad prospects of exosomes in the field of diagnosis and treatment of OS, and puts forward some suggestions for the study of the mechanism of OS chemotherapy resistance.

Methylprednisolone Promotes Mycobacterium smegmatis Survival in Macrophages through NF-κB/DUSP1 Pathway.

BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis. As an important component of host immunity, macrophages are not only the first line of defense against M. tuberculosis but also the parasitic site of M. tuberculosis in the host. Glucocorticoids can cause immunosuppression, which is considered to be one of the major risk factors for active tuberculosis, but the mechanism is unclear. OBJECTIVE: To study the effect of methylprednisolone on the proliferation of mycobacteria in macrophages and try to find key molecules of this phenomenon. METHODS: The macrophage line RAW264.7 infected by M. smegmatis was treated with methylprednisolone, and the intracellular bacterial CFU, Reactive Oxygen Species (ROS), cytokine secretion, autophagy, and apoptosis were measured. After the cells were treated with NF-κB inhibitor BAY 11-7082 and DUSP1 inhibitor BCI, respectively, the intracellular bacterial CFU, ROS, IL-6, and TNF-α secretion were detected. RESULTS: After treatment with methylprednisolone, the CFU of intracellular bacteria increased, the level of ROS decreased, and the secretion of IL-6 and TNF-α decreased in infected macrophages. After BAY 11-7082 treatment, the CFU of M. smegmatis in macrophages increased, and the level of ROS production and the secretion of IL-6 by macrophages decreased. Transcriptome high-throughput sequencing and bioinformatics analysis suggested that DUSP1 was the key molecule in the above phenomenon. Western blot analysis confirmed that the expression level of DUSP1 was increased in the infected macrophages treated with methylprednisolone and BAY 11-7082, respectively. After BCI treatment, the level of ROS produced by infected macrophages increased, and the secretion of IL-6 increased. After the treatment of BCI combined with methylprednisolone or BAY 11-7082, the level of ROS produced and the secretion of IL-6 by macrophages were increased. CONCLUSION: methylprednisolone promotes the proliferation of mycobacteria in macrophages by suppressing cellular ROS production and IL-6 secretion through down-regulating NF-κB and up-regulating DUSP1 expression. BCI, an inhibitor of DUSP1, can reduce the level of DUSP1 in the infected macrophages and inhibit the proliferation of intracellular mycobacteria by promoting cellular ROS production and IL-6 secretion. Therefore, BCI may become a new molecule for host-directed therapy of tuberculosis, as well as a new strategy for the prevention of tuberculosis when treated with glucocorticoids.

[SigE inhibits DNA damage and participates in the regulation of DNA damage repair in Mycobacterium smegmatis].

Objective To investigate the anti-DNA damage role of Sigma factor E (SigE) and its regulation mechanism of DNA damage repair in Mycobacterium smegmatis(MS). Methods The SigE gene of Mycobacterium smegmatis was cloned into plasmid pMV261 to construct recombinant plasmid pMV261(+)-SigE, and the inserted gene was verified by sequencing. The recombinant plasmid was electrically transformed into Mycobacterium smegmatis to construct SigE over-expression strain, and the expression of SigE was detected by Western blot analysis. The Mycobacterium smegmatis containing pMV261 plasmid was used as the control strain. Growth differences between the two stains were monitored by measuring the 600 nm absorbance (A600) value of the bacterial culture suspension. The survival rate differences between two kinds of strains which were treated with three kinds of DNA damaging agents including ultraviolet ray (UV), cisplatin (DDP), and mitomycin C (MMC) were detected by colony forming unit (CFU) counting assay. DNA damage repair pathways of Mycobacteria were analyzed through bioinformatics and SigE-related genes were screened. The relative expression levels of these genes possibly related to the SigE against DNA damage were detected by real-time fluorescence quantitative PCR. Results SigE over-expression strain pMV261(+)-SigE/MS was constructed and the expression of SigE in Mycobacterium smegmatis was detected. Compared with the control strain, the SigE over-expression strain grew more slowly and entered the growth plateau later; survival rate analysis found that SigE over-expression strain was more resistant to three DNA damaging agents including UV, DDP, and MMC. Bioinformatic analysis indicated that SigE gene was closely related to DNA damage repair genes recA, single-strand DNA binding protein, (ssb), and dnaE2; the expression levels of recA, dnaE2, and ssb in SigE over-expression strain all increased with varying degrees compared with those in the control strain. Conclusion SigE plays an important role in inhibiting the DNA damage of Mycobacterium smegmatis, whose mechanism is closely related to the regulation of DNA damage repair.

Derivation and comprehensive analysis of ageing-related genes in intervertebral disc degeneration for prediction and immunology.

Intervertebral disc degeneration (IDD) is triggered primarily by ageing, a process characterized by intrinsic, multifaceted and progressive characteristics. Regarding the crucial senescence genes and underlying regulatory mechanisms leading to the etiology of IDD, there is still some uncertainty. In this study, we used gene expression patterns from the GEO database to create a diagnostic model of IDD using differential ageing-related genes (DARG). We examine the relative dynamics of immune cells by single-sample gene set. On the basis of transcription factor (TF) miRNA and miRNA-mRNA pairs, the regulatory network for transcription and post-transcriptional processes was built. The active therapeutic components and Chinese herbal remedies of the main ageing genes were investigated using a network pharmacology approach. 20 DARGs were combined to create a diagnostic model, and both the training and validation sets had an area under the ROC curve of 1. We found alterations in many cell types in IDD tissue, but mainly in activated dendritic cells, type 17 T helper cells, and mast cells. We identified a regulatory axis for STAT1/miR-4306/PPARA based on the correlations between gene expression and targeting. Active substances (Naringenin and Quercetin) and herbs (Aurantii fructus and Eucommiae cortex) targeting PPARA for the treatment of IDD were discovered through network pharmacology. These results provide a theoretical framework for identifying and treating IDD. For the first time, we were able to diagnose IDD patients using 20 ageing-related indicators. At the same time, TF-miRNA-mRNA in conjunction with network pharmacology enabled the identification of prospective therapeutic targets and pharmacological processes.

Inhibition of mycobacteria proliferation in macrophages by low cisplatin concentration through phosphorylated p53-related apoptosis pathway.

BACKGROUND: Drug resistance is a prominent problem in the treatment of tuberculosis, so it is urgent to develop new anti- tuberculosis drugs. Here, we investigated the effects and mechanisms of cisplatin (DDP) on intracellular Mycobacterium smegmatis to tap the therapeutic potential of DDP in mycobacterial infection. RESULTS: Macrophages infected with Mycobacterium smegmatis were treated with DDP alone or combined with isoniazid or rifampicin. The results showed that the bacterial count in macrophages decreased significantly after DDP (≤ 6 µg/mL) treatment. When isoniazid or rifampicin was combined with DDP, the number of intracellular mycobacteria was also significantly lower than that of isoniazid or rifampicin alone. Apoptosis of infected cells increased after 24 h of DDP treatment, as shown by flow cytometry and transmission electron microscopy detection. Transcriptome sequencing showed that there were 1161 upregulated and 645 downregulated differentially expressed genes (DEGs) between the control group and DDP treatment group. A Trp53-centered protein interaction network was found based on the top 100 significant DEGs through STRING and Cytoscape software. The expression of phosphorylated p53, Bax, JAK, p38 MAPK and PI3K increased after DDP treatment, as shown by Western blot analysis. Inhibitors of JAK, PI3K or p38 MAPK inhibited the increase in cell apoptosis and the reduction in the intracellular bacterial count induced by DDP. The p53 promoter Kevetrin hydrochloride scavenges intracellular mycobacteria. If combined with DDP, Kevetrin hydrochloride could increase the effect of DDP on the elimination of intracellular mycobacteria. In conclusion, DDP at low concentrations could activate the JAK, p38 MAPK and PI3K pathways in infected macrophages, promote the phosphorylation of p53 protein, and increase the ratio of Bax to Bcl-2, leading to cell apoptosis, thus eliminating intracellular bacteria and reducing the spread of mycobacteria. CONCLUSION: DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.

Intramedullary Nail for Treatment of Proximal Humeral Fracture: A Credible Fixation in Comminuted Calcar.

OBJECTIVE: Restoration of the medial support is especially important for the treatment of proximal humeral fractures. The objective of this study was to investigate the radiographic and clinical outcomes of intramedullary nail fixation with a special focus on the presence of calcar comminution. METHODS: In this retrospective study of patients with displaced proximal humeral fractures that were treated by intramedullary nail between January 2018 and July 2021, fracture morphology and the calcar integrity were noted on preoperative radiographs. Patients were divided into two groups according to calcar integrity. During follow-up, radiological assessment and functional outcome, including the deltoid tuberosity index (DTI), neck shaft angle (NSA), visual analog scale (VAS), the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST) score, active and passive range of motion, were performed. A Student t-test and univariate logistic regression analysis was used. RESULTS: A total of 83 patients (54 female, 29 male) had complete follow-up (average, 12.8 months; range, 10 to 33 months) and functional assessment in our study. The average age was 58.6 years (range, 20 to 89 years). The mean loss of NSA was 4° (range, 0°-12°) and no significant difference was found between two groups (p = 0.27). DTI had an average of 1.50 ± 0.19 (range 1.13-2.04). Patients with intact calcar achieved greater range of forward elevation (129.06 ± 11.91 vs. 121.05 ± 11.97, p = 0.01), and higher SST scores (8.61 ± 1.85 vs. 7.37 ± 2.22, p = 0.02). Two groups showed similar outcomes in VAS, ASES score, and range of abduction. One patient demonstrated a proximal interlocking screw cutting through and osteonecrosis of the humeral head, who underwent a second surgery for screw removal. There were no cases of infection, malunion, nonunion, nerve injury, subacromial impingement, or rotator cuff tear during the study period. CONCLUSION: Intramedullary nail can favorably be used to manage proximal humeral fractures with good early radiographic and functional outcomes, even for those with comminuted calcar.

Long non-coding RNA SNHG9 regulates viral replication in rhabdomyosarcoma cells infected with enterovirus D68 via miR-150-5p/c-Fos axis.

Background: The Enterovirus D68 (EV-D68) epidemic has increased knowledge of the virus as a pathogen capable of causing serious respiratory and neurological illnesses. It has been shown that long noncoding RNAs (lncRNAs) regulate viral replication and infection via multiple mechanisms or signaling pathways. However, the precise function of lncRNAs in EV-D68 infection remains unknown. Methods: The differential expression profiles of lncRNA in EV-D68-infected and uninfected rhabdomyosarcoma (RD) cells were studied using high-throughput sequencing technology. The knockdown through small interfering RNA (siRNA) and overexpression of lncRNA SNHG9 (small ribonucleic acid host gene 9) were applied to investigate how lncRNA SNHG9 regulates EV-D68 propagation. The targeted interactions of lncRNA SNHG9 with miR-150-5p and miR-150-5p with c-Fos were validated using dual luciferase reporter system. LncRNA SNHG9 knockdown and miR-150-5p inhibitor were co-transfected with RD cells. QRT-PCR and western blot were used to detect RNA and protein levels, of c-Fos and VP1, respectively. Median tissue culture infectious dose (TCID50) was applied to detect viral titers. Results: The results demonstrated that a total of 375 lncRNAs were highly dysregulated in the EV-D68 infection model. In the EV-D68 infection model, lncRNA SNHG9 and c-Fos were increased in EV-D68-infected RD cells. However, the expression level of miR-150-5p was downregulated. In addition, overexpression of SNHG9 in RD cells resulted in decreased viral replication levels and viral titers following infection with EV-D68, and further experiments revealed that overexpression of SNHG9 inhibited the viral replication by targeting increased miR-150-5p binding and significantly increased c-Fos expression in RD cells. Conclusion: Our findings indicate that the SNHG9/miR-150-5p/c-Fos axis influences EV-D68 replication in host cells and that SNHG9 may be a possible target for anti-EV-D68 infection therapies.

High throughput sequencing of whole transcriptome and construct of ceRNA regulatory network in RD cells infected with enterovirus D68.

BACKGROUND: With the advancement of sequencing technologies, a plethora of noncoding RNA (ncRNA) species have been widely discovered, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs). However, the mechanism of these non-coding RNAs in diseases caused by enterovirus d68 (EV-D68) remains unclear. The goal of this research was to identify significantly altered circRNAs, lncRNAs, miRNAs, and mRNAs pathways in RD cells infected with EV-D68, analyze their target relationships, demonstrate the competing endogenous RNA (ceRNA) regulatory network, and evaluate their biological functions. METHODS: The total RNAs were sequenced by high-throughput sequencing technology, and differentially expressed genes between control and infection groups were screened using bioinformatics method. We discovered the targeting relationship between three ncRNAs and mRNA using bioinformatics methods, and then built a ceRNA regulatory network centered on miRNA. The biological functions of differentially expressed mRNAs (DEmRNAs) were discovered through GO and KEGG enrichment analysis. Create a protein interaction network (PPI) to seek for hub mRNAs and learn more about protein-protein interactions. The relative expression was verified using RT-qPCR. The effects of Fos and ARRDC3 on virus replication were confirmed using RT-qPCR, virus titer (TCID50/ml), Western blotting. RESULTS: 375 lncRNAs (154 upregulated and 221 downregulated), 33 circRNAs (32 upregulated and 1 downregulated), 96 miRNAs (49 upregulated and 47 downregulated), and 239 mRNAs (135 upregulated and 104 downregulated) were identified as differently in infected group compare to no-infected group. A single lncRNA or circRNA can be connected with numerous miRNAs, which subsequently coregulate additional mRNAs, according to the ceRNA regulatory network. The majority of DEmRNAs were shown to be connected to DNA binding, transcription regulation by RNA polymerase II, transcription factor, MAPK signaling pathways, Hippo signal pathway, and apoptosis pathway, according to GO and KEGG pathway enrichment analysis. The hub mRNAs with EGR1, Fos and Jun as the core were screened through PPI interaction network. We preliminarily demonstrated that the Fos and ARRDC3 genes can suppress EV-D68 viral replication in order to further verify the results of full transcriptome sequencing. CONCLUSION: The results of whole transcriptome analysis after EV-D68 infection of RD cells were first reported in this study, and for the first time, a ceRNA regulation network containing miRNA at its center was established for the first time. The Fos and ARRDC3 genes were found to hinder viral in RD cells. This study establishes a novel insight host response during EV-D68 infection and further investigated potential drug targets.

Flow-through arterialized venous free thenar flaps for palmar soft tissue defects in fingers.

OBJECTIVE: To evaluate the efficacy of venous free thenar flaps for reconstructing palmar soft tissue defects in fingers. METHODS: From December 2018 to October 2019, 11 patients with palmar soft tissue defects in fingers were treated using venous free thenar flaps. At the final follow-up, the range of thumb radial and palmar abduction on the injured side and opposite side was calculated. The total active movement (TAM) of the injured and opposite fingers and flap sensibility recovery were also recorded. RESULTS: The mean follow-up time was 13.4 months, all flaps survived, and all wounds at the donor sites healed with no skin necrosis. At the last follow-up, the average range of thumb radial abduction and thumb palmar abduction on the injured side was 96.6% and 95.9% of the value on the opposite side, respectively. The average TAM of the injured fingers was 98.2% of the value of the opposite fingers. Sensation in the flaps was restored to grade S2 to S3. CONCLUSION: Venous free thenar flaps can be alternatives for reconstructing palmar soft tissue defects in fingers.

Comparison of the modified direct closure method and skin grafting for wounds at the anterolateral thigh flap donor site.

OBJECTIVE: This study was performed to compare the modified direct closure method and traditional skin grafting for wounds at the anterolateral thigh (ALT) flap donor site. METHODS: Among 29 consecutive patients with wounds at the ALT flap donor site, 14 underwent the modified direct closure method (MDC group) and 15 underwent traditional skin grafting (SG group). The operative time, follow-up time, complications, Vancouver Scar Scale (VSS) score, and Scar Cosmesis Assessment and Rating (SCAR) score of the two groups were statistically analyzed. RESULTS: The mean follow-up times in the MDC and SG group were 16.1 and 16.7 months, respectively. Two patients showed partial skin necrosis after skin grafting, but the remaining patients' wounds healed uneventfully. The operative time in the MDC group was an average of about 64 minutes shorter than that in the SG group. The average VSS and SCAR scores in the MDC group were 2.1 and 3.0 points lower, respectively, than those in the SG group. CONCLUSIONS: Compared with traditional skin grafting, the modified direct closure method is more efficient for repair of wounds at the ALT flap donor site because of its shorter operative time, better postoperative appearance of the donor site, and higher patient satisfaction.

Potential superiority of periarticular injection in analgesic effect and early mobilization ability over femoral nerve block following total knee arthroplasty.

PURPOSE: Pain management after total knee arthroplasty (TKA) should permit early knee mobilization with minimal pain. Periarticular injection (PAI) with local anaesthetics has been recently discussed as a protocol of pain control. The purpose of this review of the literature was to evaluate the efficacy of PAI in comparison with femoral nerve block (FNB). METHODS: A literature search was performed in PubMed, EMBASE, the OVID database and the Cochrane Library databases. Risk of bias was assessed using the Cochrane collaboration tool. Outcomes of interest included narcotic consumption, pain score, early mobilization ability, length of stay and adverse effects or events. RESULTS: Research identified 918 articles, of which six with a total of 284 knees, met the inclusion criteria and were eligible for the current study. Conflicting evidence was found in terms of narcotic consumption on the postoperative day 1 and early mobilization ability. Total narcotic consumption, pain score in the first 2 days after surgery, length of stay and adverse effects or events showed no difference between two groups. Lower pain score on the day of surgery was detected after PAI. When compared to continuous FNB, patients in PAI group showed a tendency to achieving better ability of early mobilization. CONCLUSIONS: In consideration of its relatively simple practice and its potential in analgesic effects or early mobilization ability, PAI had superiority to FNB in the management of pain control after TKA. Before PAI could be widely used in clinical practice after TKAs, further investigations would be necessary to confirm or refute our observed results and to unify the protocol of PAI. LEVEL OF EVIDENCE: I.

No difference in mechanical alignment and femoral component placement between patient-specific instrumentation and conventional instrumentation in TKA.

PURPOSE: There is a rising interest in the use of patient-specific instrumentation (PSI) during total knee arthroplasty (TKA). The goal of this meta-analysis was to compare PSI with conventional instrumentation (CI) in patients undergoing TKA. METHODS: A literature search was performed in PubMed, Embase, Springer, Ovid, China National Knowledge Infrastructure, and the Cochrane Library. A total of 10 randomized controlled studies involving 837 knees comparing outcomes of PSI TKAs with CI TKAs were included in the present analysis. Outcomes of interest included component alignment, surgical time, blood loss, and hospital stay. RESULTS: The results presented no significant differences between the two instrumentations in terms of restoring a neutral mechanical axis and femoral component placement. However, their differences have been noted regarding the alignment of the tibial component in coronal and sagittal planes. Also, 3 min less surgical time was used in PSI patients. CONCLUSIONS: Based on these findings, PSI appeared not to be superior to CI in terms of the post-operative mechanical axis of the limb or femoral component placement. Despite a statistical difference for operative duration, the benefit of a small reduction in surgical time with PSI is clinically irrelevant. LEVEL OF EVIDENCE: Therapeutic study (systematic review and meta-analysis), Level I.

No clinical benefit of high-flex total knee arthroplasty. A meta-analysis of randomized controlled trials.

The application of high-flex prosthesis in total knee arthroplasty (TKA) is an area of continuing debate. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs). A literature search was performed in PubMed, EMBASE and the Cochrane database. 10 trials involving 1230 knee joints were eligible for our meta-analysis. No significant difference was observed between the two designs regarding postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate. Moreover, the advantage of high-flex implants for patients with high preoperative range remained not statistically significant and high-flex design in NexGen system showed a marginal improvement in the postoperative range of flexion. Based on current findings, high-flex prosthesis did not appear to confer any benefit as compared to standard prosthesis.