Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

[Short-term clinical efficacy observation of lesion removal, bone graft fusion, and external brace treatment for late-stage wrist tuberculosis].

OBJECTIVE: To observe the clinical efficacy of lesion removal, bone grafting, fusion, and external fixation in the treatment of late-stage wrist tuberculosis. METHODS: From October 2015 to May 2019, 25 patients with late-stage wrist tuberculosis were treated using lesion removal, bone grafting, fusion, and external fixation. Among these patients, there were 14 males and 11 females, aged from 40 to 74 years old, with an average age of (60.72±8.45) years old. The duration of the disease ranged from 5 to 24 months, with an average of (11.52±7.61) months. There were 11 cases of left wrist tuberculosis and 14 cases of right wrist tuberculosis, with 5 cases accompanied by sinus formation. Postoperative regular anti-tuberculosis treatment was continued. Visual analogue score (VAS), inflammatory indicators, Gartland-Werley wrist function score, and upper limb function score were observed before and after treatment. RESULTS: All 25 patients were followed up for ranging from 12 to 36 months with an average of (19.7±6.3) months. At the latest follow-up, all wounds were healed satisfactorily, and there was no recurrence of tuberculosis or infection. VAS at one week before operation and three months after operation were (5.16±1.14) score and (1.68±0.80) score respectively. One week before operation and three months after operation, erythrocyte sedimentation rate (ESR) was (44.20±20.56) mm·h-1 and (14.44±1.14) mm·h-1, and C-reactive protein (CRP) was (12.37±7.95) mg·L-1 and (4.3±3.37) mg·L-1. The differences in all three data sets were statistically significant (P<0.01). According to Gartland-Werley wrist function scoring, the scores at one week before operation and one year after operation were (21.32±3.44) and (14.96±1.37) respectively, showed a statistically significant difference (P<0.01). According to the upper limb function score (disabilities of the arm, shoulder, and hand, DASH), the score was (70.52±7.95) at one week before operation and(28.84±2.30) at one year after operation. The difference was statistically significant (P<0.01). At the latest follow-up, no patient had a recurrence of tuberculosis. CONCLUSION: The short-term clinical efficacy of treating wrist tuberculosis with lesion removal, bone grafting, fusion, and external fixation is satisfactory.

Simulation of the ligand-leaving process of the human heat shock protein.

The human heat shock protein plays a critical role in various diseases and is an important target for pharmacological modulation. Simulation of conformational changes and free energy profiles of the human heat shock protein derived by the ligand-leaving process is a challenging issue. In this work, steered molecular dynamics simulation was adopted to simulate the ligand-leaving process. Two composite systems of heat shock protein NHSP90 and small molecules 6FJ and 6G7 are selected as research objects. The free energy during the leaving of ligand small molecules is calculated using conventional molecular dynamics simulation, steered molecular dynamics simulation (SMD), and the umbrella sampling method. We found that the a slower pulling velocity (0.001 nm ns-1) will result in 2.19 kcal mol-1, and the umbrella sampling method gives a value of 3.26 kcal mol-1 for the free energy difference for the two systems, which reasonably agrees with experimental results. A faster-pulling velocity (0.01 nm ns-1) leads to a large overestimation of free energy. At the same time, the conformational analysis indicated that the faster pulling velocity may lead to the conformational change of NHSP90, which was proved to be false by the slower pulling velocity and the umbrella sampling method.

Reduction of lymphocyte count at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study.

Introduction: Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods: All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions: Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.

Application of integrated problem-based learning combined with lecture-based classroom teaching in undergraduate medical education: An effective teaching model in a Medical School in China.

The problem-based learning (PBL) is increasingly used in undergraduate education. However, the application of integrated PBL to medical undergraduate education has not been well assessed. An observational study was designed to compare integrated PBL combined with lecture-based classroom (LBC) with traditional LBC teaching in 2 semesters of a Medical School in China. This study was conducted from March 2021 to July 2022. A total of 118 undergraduates majoring in clinical medicine were randomly allocated in 2 groups, 1 group receiving the integrated PBL + LBC teaching (experimental group, n = 60) and another group receiving LBC teaching (control group, n = 58). The experimental group attended the integrated PBL courses for the basic and clinical medicine conducted in the 6th and 8th semesters, respectively, as well as taking the LBC courses. The experimental group was required to preview the course materials before class, make presentations in class and take online feedback questionnaires after class, while the control group was required to preview the textbooks and listen to the traditional LBC courses. The students' scores of these 2 groups were compared, and feedback questionnaires were performed to evaluate the effectiveness of the experimental group over the control group. Results showed that the experimental group scored significantly higher than the control group in Clinical Skills (95% confidence interval [CI] 4.19-5.89), Internal Medicine I (95% CI: 1.85-9.93), Internal Medicine II (95% CI: 8.07-15.90), Introduction to Surgery (95% CI: 5.08-10.25), Surgery (General Surgery) (95% CI: 7.82-12.72), Surgery (Specialty) (95% CI: 6.47-9.97), and Clinical Medical Level Test (95% CI: 1.60-5.15) (all P < .01). In the feedback questionnaires of integrated PBL, up to 80% and 90% of students were satisfied with the teaching methods and lecturers, respectively. More than 80% of students agreed that the integrated PBL improved their abilities to learn independently, understand knowledge, and to raise, analyze and solve problems. In terms of stress in and out of class, a small number of students, <36.7%, felt stressed. The integrated PBL combined with LBC is an effective teaching approach, which may provide new ideas for teaching research and reform on undergraduate medical education in clinical medicine specialty and other medical majors.

The Efficacy and Safety of Bionic Tiger Bone Powder for the Treatment of Knee Osteoarthritis in Early Stage: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

Objective: This study evaluated the efficacy and safety of bionic tiger bone powder (Jintiange) in comparison to placebo in treating knee osteoarthritis osteoporosis. Methods: A total of 248 patients were randomly allocated to a Jintiange group or a placebo group, undergoing 48 weeks of double-blind treatment. The Lequesne index, clinical symptoms, safety index (adverse events), and Patient's Global Impression of Change score were recorded at pre-determined time intervals. All P values ≤ .05 were deemed statistically significant. Results: Both groups showed a decreasing trend in the Lequesne index, with the Jintiange group's reduction significantly larger from the 12th week (P ≤ .01). Similarly, the effective rate of Lequesne score in the Jintiange group was significantly higher (P < .001). After 48 weeks, clinical symptom score differences between the Jintiange group (2.46 ± 1.74) and the placebo group (1.51 ± 1.73) were statistically significant (P < .05), as were differences in the Patient's Global Impression of Change score (P < .05). Adverse drug reactions were minimal with no significant difference between the groups (P > .05). Conclusion: Jintiange demonstrated superior efficacy over placebo in treating knee osteoporosis, with comparable safety profiles. Findings warrant further comprehensive real-world studies.

Fibulin-2: A potential regulator of immune dysfunction after bone trauma.

OBJECTIVES: To reveal the relationship between the fibulin-2 protein and immune dysfunction after bone trauma. METHODS: Individuals who were admitted to the study were divided into a bone trauma group, a recovered from bone trauma group and a volunteer without bone trauma group based on the reason for admission. Fibulin-2 levels in the three groups were compared. Fibulin-2-knockout (fibulin-2-/- ) mice and wild-type (WT) mice were used to detect susceptibility to infection. Hematoxylin and eosin (HE) staining and immunohistochemical staining were employed to observe pathological changes in each organ from fibulin-2-/- mice and WT mice. RESULTS: In total, 132 patients were enrolled in this study. The fibulin-2 level in the bone trauma group was lower than that in the recovered bone trauma group (3.39 ± 1.41 vs. 4.30 ± 1.38 ng/mL, t = 2.948, p < .05) and also lower than that in the volunteers without bone trauma group (3.39 ± 1.41 vs. 4.73 ± 1.67 ng/mL, t = 4.135, p < .05). Fibulin-2-/- mice are more prone to infection. Compared with those in WT mice, spleen function and thymus function in fibulin-2-/- mice were impaired. Immunohistochemical staining revealed that compared with those in WT mice, significantly fewer CD4+ T cells, CD8+ T cells, and CD19+ B cells were noted in the spleen and thymus of fibulin-2-/- mice. CONCLUSIONS: The plasma fibulin-2 level was lower in patients with bone trauma. Decreased fibulin-2 is associated with immune dysfunction after bone trauma.

A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden's J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

Sebaceous Carcinoma of the Submandibular Gland a Case Report and Review of the Literature.

Objective: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature. Methods and Results: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months. Conclusion: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Phylogenetic implications and characterization of the chloroplast genome of Atractylodes macrocephala (Compositae), an herb species to China.

The rhizome of Atractylodes macrocephala is one of the most commonly used herbs in China. In this paper, we presented the complete chloroplast genome of A. macrocephala. The chloroplast genome of A. macrocephala is 153,256 bp in length as the circular, which harbors a large single-copy (LSC) region 84,291 bp, a small single-copy (SSC) region of 18,675 bp and separated by a pair of inverted-repeat (IR) regions of 25,145 bp for each one. The overall nucleotide content of the chloroplast genome is 37.7% GC content. This chloroplast genome contains 125 genes, which includes 88 protein-coding genes (PCGs), 29 transfer RNA (tRNAs) and 8 ribosome RNA (rRNAs). Phylogenetic implications based on chloroplast genomes of 16 the family Compositae plant species indicated that Atractylodes macrocephala was closely related to Atractylodes lancea in the family Compositae by the Maximum-Likelihood (ML) method.

A long-term survival rat model of spinal cord ischemia injury: Thoracic aortic occlusion combined with aortic bypass circulation.

OBJECTIVE: This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. METHODS: The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru - T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. RESULTS: After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference (p < 0.05). CONCLUSION: Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.

Single-Cell Transcriptomics Analysis of the Pathogenesis of Tendon Injury.

Tendon injury repair has been a clinical challenge, and little is known about tendon healing scar generation, repair, and regeneration mechanisms. To explore the cellular composition of tendon tissue and analyze cell populations and signaling pathways associated with tendon repair, in this paper, single-cell sequencing data was used for data mining and seven cell subsets were annotated in the tendon tissue, including fibroblasts, tenocytes, smooth muscle cells, endothelial cells, macrophages, T cells, and plasma cells. According to cell group interaction network analysis, pattern 4 composed of macrophages was an important communication pattern in tendon injury. Furthermore, the heterogeneity of M1 macrophages in tendons, the correlation of KEGG enriched pathway with inflammatory response, and the core regulatory role of the transcription factor NFKB and REL were observed; in addition, the heterogeneity of T cell isoforms in tendons was found and indicated that different isotypes of T cells involve in different roles of tendon injury and repair. This study demonstrated the heterogeneity of M1 macrophages and T cells in the tendon tissue, being involved in different physiological processes such as tendon injury and healing, providing new thinking insights and basis for subsequent clinical treatment of tendon injury.

Comparison of Affected-Vertebra Fixation of Cortical Bone Trajectory Screw and Pedicle Screw for Lumbar Tuberculosis: A Minimum 3-Year Follow-Up.

Purpose: This study is aimed at comparing the clinical efficacy of cortical bone trajectory (CBT) screw fixation and pedicle screw (PS) fixation of the affected vertebrae in lumbar tuberculosis. Methods: We retrospectively analyzed the outcomes in 52 patients (27 cases in the CBT group, 25 cases in the PS group) with lumbar TB who underwent posterior affected-vertebra fixation combined with anterior debridement and bone grafting. The intraoperative blood loss, operative time, visual analog scale (VAS) scores for incision pain and leg pain, Japanese Orthopedic Association (JOA) score, bone grafting fusion, and complications were recorded. Results: All patients were followed up for 35-52 months and achieved good clinical outcomes. There were no differences between the two groups in the operative time, intraoperative blood loss, JOA score, bone grafting fusion, and complications. However, there was a significant difference between the two groups in VAS scores for incision pain on the 1st day and 3rd day after surgery. At the last follow-up, JOA scores were significantly improved in both groups compared to the preoperation. Conclusion: This retrospective study confirmed that both the affected-vertebra CBT screw fixation and PS fixation for lumbar TB via posterior and anterior approaches could achieve satisfactory outcomes, while the former resulted in better improvement for postoperative VAS scores.

C-arm Fluoroscopy-Guided Percutaneous Needle Biopsy for the Diagnosis of Spinal Infection: A Study of 203 Consecutive Patients.

C-arm fluoroscopy-guided percutaneous needle biopsy (PNB) is a commonly used biopsy method, which shows similar diagnostic outcomes to CT-guided biopsy. This study aimed to evaluate the diagnostic value of C-arm fluoroscopy-guided percutaneous needle biopsy (PNB) for spinal infection. A total of 30 male and 73 female patients with suspected spinal infection were enrolled. Among enrolled patients, the spinal lesion was mainly located in the thoracic (T3-T12, 48.28%) and lumbar vertebra (L1-L5, 46.80%), and T12 was the most frequently involved site. C-arm fluoroscopy-guided PNB was performed for the isolation of biopsy samples in these patients. The overall detection rate of pathological changes in bone tissues was 94.1% (191/203), including 92 granulomata with caseous necrosis, 81 inflammatory tissues, 18 tumor tissues, and 12 bone tissues without visible pathological changes. After excluding the tumors, the detection rate of pathogenic microorganisms in liquid tissues was 50.27% (93/185), including 68 Mycobacterium tuberculosis, and 25 other microorganisms. Spinal tuberculosis was diagnosed in 118 (58%) cases, and nonspecific spinal infection with microorganisms other than Mycobacterium tuberculosis was diagnosed in 25 (12.7%) cases. Definite diagnosis was not determined in the left 42 (20.5%) patients with neither positive pathological nor pathogenic results. C-arm fluoroscopy-guided PNB is effective in the detection of pathological changes and pathogenic microorganisms, which is a practical approach for the diagnosis of spinal infection with high accuracy.

Dual antioxidant activity and the related mechanisms of a novel pentapeptide GLP4 from the fermented mycelia of Ganoderma lingzhi.

Oxidative stress causes chronic inflammation, and mediates various diseases. The discovery of antioxidants from natural sources is important to research. Here we identified a novel antioxidant peptide (GLP4) from Ganoderma lingzhi mycelium and investigated its antioxidant type and potential protective mechanisms. Through free radical scavenging assay, active site shielding validation, superoxide dismutase (SOD) activity assay, and lipid peroxidation assay, we demonstrated that GLP4 was a novel protective agent with both direct and indirect antioxidant activities. GLP4 could directly enter human umbilical vein endothelial cells (HUVECs) as an exogenous substance. Meanwhile, GLP4 promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and activated the Nrf2/antioxidant response element (ARE) signaling pathway, exhibiting antioxidant and anti-apoptotic cytoprotective effects on hydrogen peroxide (H2O2)-induced HUVECs. Pull-down experiments of GLP4 target proteins, bioinformatics analysis and molecular docking further revealed that GLP4 mediated Nrf2 activation through binding to phosphoglycerate mutase 5 (PGAM5). The results suggested that GLP4 is a novel peptide with dual antioxidant activity and has promising potential as a protective agent in preventing oxidative stress-related diseases.

[Comparison of nano-hydroxyapatite/polyamide 66 bioactive support and autologous iliac bone in bone grafting and fusion for elderly patients with lumbar tuberculosis].

Objective: To investigate the safety of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bioactive support in bone grafting and fusion for elderly patients with lumbar tuberculosis, and to analyze its effectiveness and advantages by comparing with autologous iliac bone grafting. Methods: A retrospective analysis was performed on 48 elderly patients with lumbar tuberculosis who met the selection criteria between January 2017 and January 2020. The patients all underwent one-stage posterior pedicle screw internal fixation combined with anterior lesion removal and bone grafting and fusion, of which 23 cases applied n-HA/PA66 bioactive support+allogeneic bone graft (n-HA/PA66 group) and 25 cases applied autologous iliac bone graft (autologous iliac bone group). There was no significant difference between the two groups in gender, age, bone density, disease duration, lesion segment, and preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Cobb angle ( P>0.05). The operation time, intraoperative blood loss, and postoperative complications, as well as the VAS score, JOA score, American Spinal Injury Association (ASIA) spinal cord injury grading, Cobb angle, and bone fusion were recorded and compared between the two groups. Results: The operations were completed successfully in both groups. n-HA/PA66 group had significantly less operation time and intraoperative blood loss than the autologous iliac bone group ( P<0.05). All patients were followed up 12-24 months, with an average of 15.7 months. And the difference in follow-up time between the two groups was not significant ( P>0.05). Postoperative complications occurred in 3 cases (13%) in the n-HA/PA66 group and 10 cases (40%) in the autologous iliac group, and the difference in the incidence of complications between the two groups was significant ( χ 2=4.408, P=0.036). The postoperative VAS scores and JOA scores significantly improved when compared with the preoperative scores in both groups ( P<0.05), and the difference was significant ( P<0.05) between 2 weeks after operation and the last follow-up. The difference in VAS score at 2 weeks after operation was significant between the two groups ( P<0.05), and there was no significant difference ( P>0.05) at the other time points. At last follow-up, according to the ASIA grading, the effective improvement rate was 86% (18/21) in the n-HA/PA66 group and 90% (18/20) in the autologous iliac group, with no significant difference ( χ 2=0.176, P=0.675). Imaging review showed that grade Ⅰ bony fusion was obtained in both groups, and the fusion time of bone graft in the n-HA/PA66 group was significantly longer than that in the autologous iliac bone group ( P<0.05). There was no significant difference in the Cobb angle at each time point between the two groups ( P>0.05). No recurrence of tuberculosis, loosening or fracture of the internal fixator, or displacement of the bone graft was observed during follow-up. Conclusion: In elderly patients with lumbar spine tuberculosis, the n-HA/PA66 bioactive support combined with allogeneic bone graft can effectively restore and maintain the fusion segment height and physiological curvature of the lumbar spine, and the fusion rate of bone graft is similar to that of autologous iliac bone, which can achieve better effectiveness.

A Clinical Diagnostic Study: Fibulin-2 is a Novel Promising Biomarker for Predicting Infection.

INTRODUCTION: Infection remains a major cause of morbidity and mortality in hospital. As uncontrolled early infection may develop into systemic infection and eventually progress to sepsis, it is important to address infection at an early stage. Furthermore, early detection and prompt diagnosis of infection are the basis of clinical intervention. However, as a result of the interference of complex aetiologies, including fever and trauma, problems regarding the sensitivity and specificity of current diagnostic indices remain, such as for C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), neutrophil ratio (NEU%), interleukin-6 (IL-6) and D-dimer. As a result, there is an urgent need to develop new biomarkers to diagnose infection. METHODS: From January to October 2021, consecutive patients in the emergency department (ED) were recruited to investigate the feasibility of fibulin-2 as a diagnostic indicator of early infection. Fibulin-2 concentrations in plasma were determined with enzyme-linked immunosorbent assay (ELISA). The performance of fibulin-2 for predicting infection was analysed by receiver operating characteristic (ROC) curves. RESULTS: We found that the plasma fibulin-2 level was elevated in patients with infection compared with those without infection. ROC curve analysis showed that the area under the curve (AUC) for fibulin-2 was 0.712. For all patients included, the diagnostic ability of fibulin-2 (AUC 0.712) performed as well as CRP (AUC 0.667) and PCT (AUC 0.632), and better than WBC (AUC 0.620), NEU% (AUC 0.619), IL-6 (AUC 0.561) and D-dimer (AUC 0.630). In patients with fever, fibulin-2 performed as well as PCT and better than the other biomarkers in infection diagnosis. In particular, fibulin-2 performed better than all these biomarkers in patients with trauma. CONCLUSION: Fibulin-2 is a novel promising diagnostic biomarker for predicting infection.

Lignans and sesquiterpenes from Schisandra tomentella A. C. Smith.

This is the first phytochemical investigation of Schisandra tomentella A. C. Smith. 11 lignans and 8 sesquiterpenoids, were isolated from the stems of S. tomentella, including two undescribed lignans, tomentaschinins A-B (1-2), and two new sesquiterpenoids, tomentaschinnes A-B (3-4). Their structures were elucidated based on the interpretation of their spectroscopic data. Cytotoxicity and MDR reversal effect of these compounds were screened on multidrug resistance cancer cell line MCF-7/ADR, and results showed gomisin M2 (7) could promote the efficacy of adriamycin against MCF-7/ADR.

Fungal periprosthetic joint infection: Rare but challenging problem.

Periprosthetic joint infection (PJI) is the most difficult complication following total joint arthroplasty. Most of the etiological strains, accounting for over 98% of PJI, are bacterial species, with Staphylococcusaureus and Coagulase-negative staphylococci present in between 50% and 60% of all PJIs. Fungi, though rare, can also cause PJI in 1%-2% of cases and can be challenging to manage. The management of this uncommon but complex condition is challenging due to the absence of a consistent algorithm. Diagnosis of fungal PJI is difficult as isolation of the organisms by traditional culture may take a long time, and some of the culture-negative PJI can be caused by fungal organisms. In recent years, the introduction of next-generation sequencing has provided opportunity for isolation of the infective organisms in culture-negative PJI cases. The suggested treatment is based on consensus and includes operative and non-operative measures. Two-stage revision surgery is the most reliable surgical option for chronic PJI caused by fungi. Pharmacological therapy with antifungal agents is required for a long period of time with antibiotics and included to cover superinfections with bacterial species. The aim of this review article is to report the most up-to-date information on the diagnosis and treatment of fungal PJI with the intention of providing clear guidance to clinicians, researchers and surgeons.