Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Purpose::The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.Methods::We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. Results::Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F= 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F= 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F= 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F= 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F= 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F= 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. Conclusions::CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Purpose::Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.Methods::The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error ( p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3. Results::For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit ( p = 0.001), red blood count and hemoglobin ( p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit ( p = 0.001), red blood count and hemoglobin ( p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738. Conclusion::It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Purpose::To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.Methods::This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log 2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Results::Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.Conclusions::Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Purpose::Traumatic lumbar hernia (TLH) constitutes a protrusion of content through a defect in the posterior abdominal wall, as a result of injury. This rare entity has been described in limited number of cases.Methods::A systematic review of the literature was performed according to the meta-analysis of observational studies in epidemiology guidelines. The English literature from 1990 until 2021 was reviewed, using PubMed, EMBASE and Google Scholar bibliographic databases, to identify case reports and case series with patients that were diagnosed with TLH. For each eligible study, demographics, clinical presentation, hernia characteristics, preoperative imaging investigations, operation details, and postoperative data were extracted for assessment. Statistical analysis was performed on SPSS, version 20.0.Results::A total of 62 studies were included for review, with 164 patients with TLH. Mean age was (42.6 ± 14.3) years (47.6% males, 31.1% females, gender not specified in 35 cases). Mean diameter of hernia neck was (6.3 ± 3.1) cm, while the triangles of Petit and Grynfeltt were affected in 74.5% and 14.6%, respectively. Patients diagnosed in the emergency setting account for 54.2%, with CT scan establishing diagnosis in all but one case (97.7%). A delayed diagnosis was made in 45.8%, at a mean 1 year following trauma. Flank bulging (82.8%) and chronic back pain (34.3%) were the most frequent symptoms. In both delayed and acute group, open surgery (63.6% and 92.3%, respectively) was the preferred surgical approach. Postoperative complications were reported in 11.4% of acute and 15.0% of delayed patients. Hernia recurrence was 7%.Conclusions::TLH is uncommon with 164 cases described since 1990. CT scan is the gold standard in diagnosis. Open surgery is generally the preferred approach, particularly in the emergency setting. Acute TLH can be treated either by primary suture repair or mesh, depending on the local conditions, whereas delayed cases usually require a mesh.

Purpose::Many techniques have been described for the reconstruction of chronic lateral collateral ligament (LCL) rupture with different autograft options. The advantages of percutaneous LCL reconstruction include small incisions, minimal soft tissue disruption, less postoperative pain, and speedy rehabilitation and recovery. The aim of this study was to report the functional outcome of percutaneous LCL reconstruction and overall patient satisfaction in Africans.Methods::This prospective and interventional study involving 51 patients with chronic LCL rupture who had percutaneous LCL reconstruction using peroneus longus autograft was conducted between January 2021 and December 2022 in National Orthopaedic Hospital, Dala-Kano, Nigeria. The inclusion criteria were patients between the ages of 18 and 45 years with chronic isolated LCL and not more than 1 injury of knee ligament. Exclusion criteria were active infection, and multi-ligament knee injury requiring 2-staged surgery. The knee functions were assessed preoperatively, 3 months, 6 months, and 12 months postoperatively using the Lysholm scoring system. Patient satisfaction with the outcome of the treatment was assessed using a 5-point Likert scale. Relevant information was recorded into Microsoft Excel sheet and data was analyzed using SPSS version 23.0 for windows. The paired samples t-test was used to compare the clinical outcomes as continuous variables. Statistical significance was considered at p < 0.05. Results::The mean age of the patients was (30.10 ± 5.90) years. The median time from injury to surgery was 7 months (ranging from 3 to 28 months). The mean follow-up period was (14.07 ± 3.13) months. The mean preoperative and 1-year postoperative Lysholm scores were 44.33 ± 12.97 and 97.96 ± 1.23, respectively.Conclusion::Percutaneous LCL reconstruction using peroneus longus autograft significantly improves patient knee function and results in excellent patient satisfaction.

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

Purpose::The role of topical vancomycin in fracture-related infection (FRI) is debatable. Very few studies have reported their efficacy in open and high-risk extremity fractures. This study aimed to assess topical vancomycin's role in reducing FRI in closed fractures undergoing open surgical intervention with an implant.Methods::This prospective randomized cohort study was carried out between February 2021 to January 2022. Patients with isolated closed fractures, who were planned for open reduction and internal fixation within 2 weeks from the time of injury were included for this study. The data collected included age, gender, socioeconomic status, mechanism of injury, diagnosis, Tscherne classification, and time interval to take up for surgery. Patients were randomized into the intervention and control groups using the block randomization technique. The control group received only systemic antibiotic prophylaxis, whereas the intervention group received topical application of vancomycin powder in the surgical wound alongside systemic antibiotic prophylaxis. The primary outcome measure was the incidence of FRI among these individuals. Clinical and radiological findings and culture reports (in cases with infection) were recorded during the post-operative period and at 6 weeks of follow-up. All relevant statistical calculations were done using STATA statistical/data analysis-parallel edition version 16.0 (StataCorp LLC). The quantitative variables like age and duration of the surgery were assessed for normalcy by Shapiro-Wilk W test. An independent samples t-test with equal variances was applied to the age data. Fisher's exact test was used for the analysis of the primary outcome measure (presence of FRI following surgery), and "Risk of FRI" and "Risk difference" between the 2 groups was calculated. The strength of the association between qualitative variables was assessed using the Fisher's exact and Chi-square tests, respectively. Results::There were 88 patients included in this study. No statistical significance was found about FRI between both groups ( p = 0.494). At 6 weeks following surgery, no incidence of infection was observed in the intervention group. Two infections (4.5%) were found in the control group, with positive cultures reported in one of them but none in the treatment group. Radiologically, 15.9% of patients in the control group showed lysis around the implant compared to 2.3% in the intervention group. Impaired fracture healing was observed in 22.7% of patients in the intervention group compared to 15.9% in the control group. Conclusion::Applying topical vancomycin in closed fractures undergoing open reduction and internal fixation does not significantly reduce the incidence of FRI until the end of 6 weeks following surgery.