α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.

Unilateral biportal endoscopy via two different approaches for upper lumbar disc herniation: a technical note.

BACKGROUND: The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH). METHODS: From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up. RESULTS: All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment. CONCLUSIONS: The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application.

Serum lipidomics-based study of electroacupuncture for skin wound repair in rats.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham-operated group. There were 115 differential metabolites in the model versus electro-acupuncture group. 117 differential metabolites in the electro-acupuncture versus sham-operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.

Electroacupuncture promotes skin wound repair by improving lipid metabolism and inhibiting ferroptosis.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with 12 rats in each group. After the intervention, local skin tissues were collected for lipid metabolomics analysis, wound perfusion and ferroptosis-related indexes were detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 37 differential metabolites shared by the three groups, mainly phospholipids, lysophospholipids, glycerides, acylcarnitine, sphingolipids and fatty acids, and they could be back-regulated after electroacupuncture. The recovery of blood perfusion and wound healing was faster in the electroacupuncture group than in the model group (p < 0.05). The levels of GPX4, FTH1, SOD and GSH-PX, which are related to ferroptosis, were higher in the electroacupuncture group than in the model group (p < 0.05). The levels of ACSL4 and MDA were lower in the electroacupuncture group than in the model group (p < 0.05). Electroacupuncture may promote skin wound repair by improving lipid metabolism and inhibiting ferroptosis in local tissues.

Feasibility of repairing skin defects by VEGF165 gene-modified iPS-HFSCs seeded on a 3D printed scaffold containing astragalus polysaccharide.

The preparation of biodegradable scaffolds loaded with cells and cytokine is a feature of tissue-engineered skin. IPSCs-based tissue-engineered skin treatment for wound repair is worth exploring. Healthy human skin fibroblasts were collected and reprogrammed into iPSCs. After gene modification and induction, CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP were obtained and identified by a combination of immunofluorescence and RT-qPCR. Astragalus polysaccharide-containing 3D printed degradable scaffolds were prepared and co-cultured with VEGF165 gene-modified iPS-HFSCsGFP , and the biocompatibility and spatial structure of the tissue-engineered skin was analysed by cell counting kit-8 (CCK8) assay and scanning electron microscopy. Finally, the tissue-engineered skin was transplanted onto the dorsal trauma of nude mice, and the effect of tissue-engineered skin on the regenerative repair of total skin defects was evaluated by a combination of histology, immunohistochemistry, immunofluorescence, RT-qPCR, and in vivo three-dimensional reconstruction under two-photon microscopy. CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP , close to the morphology and phenotype of human-derived hair follicle stem cells, were obtained. The surface of the prepared 3D printed degradable scaffold containing 200 µg/mL astragalus polysaccharide was enriched with honeycomb-like meshwork, which was more conducive to the proliferation of the resulting cells. After tissue-engineered skin transplantation, combined assays showed that it promoted early vascularization, collagen and hair follicle regeneration and accelerated wound repair. VEGF165 gene-modified iPS-HFSCsGFP compounded with 3D printed degradable scaffolds containing 200 µg/mL astragalus polysaccharide can directly and indirectly participate in vascular, collagen, and hair follicle regeneration in the skin, achieving more complete structural and functional skin regenerative repair.

Single-cell RNA-seq reveals altered NK cell subsets and reduced levels of cytotoxic molecules in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune disease with unknown aetiology. To unravel the mechanisms mediating AS pathogenesis, we profiled peripheral blood mononuclear cells (PBMCs) from AS patients and healthy subjects using 10X single-cell RNA sequencing. The frequencies of immune cell subsets were evaluated by flow cytometry. NK cells were purified from PBMCs using isolation kit and were examined for gene expression by RT-qPCR. Plasma levels of cytolytic molecules were examined by enzyme-linked immunosorbent assay. Compared to healthy controls, AS patients showed a significant decrease in total NK cells as well as CD56dim NK subset, whereas CD56bright NK cells were increased. Additionally, impaired expression of cytotoxic genes in NK cells of AS patients was observed by bioinformatics algorithm and verified by RT-qPCR and flow cytometry. Consistent with changes in transcriptomics, we found decreased plasma levels of granzymes, but not granulysin, in AS patients. Furthermore, Pearson correlation analysis revealed a negative correlation between plasma GZMB levels and disease activity (r = -0.5275, p = 0.0358). No correlation was observed between plasma cytolytic molecules and biochemical indexes (ESR and CRP). Our findings uncover altered NK cell subsets and cytotoxic profiles in peripheral circulation of AS patients at single-cell resolution.

The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation.

House dust mite (HDM) sublingual immunotherapy (SLIT) in the form of SLIT-tablets is now an established treatment option for HDM allergy and HDM-induced allergic asthma. In SLIT-tablet immunotherapy allergen extracts are formulated as dry tablets and administered under the tongue where it must be solubilized in saliva in order to be able to interact with the immune system of the sublingual mucosa. Solubilization of the extract must occur within a short time span of about one minute after administration, determined by the sublingual holding time recommended by the manufacturer. Currently, two types of HDM SLIT-tablets are available. Both tablet types contain natural HDM extracts from two common HDM species as the active ingredient, but differ with regard to formulation as one tablet type is based on a freeze-dried tablet formulation while the other is based on a compressed formulation. HDM extracts contain a number of major and minor allergens, which in combination provide the allergenic activity that drives the immunological response and in turn the clinical efficacy of the tablets. Here, a biologically relevant human immunoglobulin E (IgE)-based assay is used to compare the ability of the two HDM SLIT-tablet types to deliver HDM allergenic reactivity from the dry tablet into soluble form. The experiments demonstrate that the freeze-dried formulation delivers HDM allergenic activity into solution faster and more efficiently than the compressed formulation.

Comparison of the Allergenic Potency of House Dust Extract and House Dust Mite Allergen Extract for Subcutaneous Allergen Immunotherapy.

Subcutaneous allergen immunotherapy (SCIT) with non-standardized house dust (HD) extracts has been used in Japan since 1963 for house dust mite (HDM)-allergic patients. Since the potencies of HD extracts are unknown, the allergenic potency of HD extracts was examined by comparing with a standardized HDM allergen extracts. The major allergen content of HDM in the extracts was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). The immunoglobulin E (IgE) inhibitory activities of the extracts were measured by a competitive ELISA. The extract concentrations giving 50% inhibition of IgE binding (log10 IC50) were determined from dose-response curves and defined as inhibitory activities. A linear regression line was constructed from the log10 IC50 values of the standardized HDM extract to interpolate the relative potency of the HD extract with strength of 1 : 10 w/v (HD 1 : 10). The amounts of major allergens (Der f 1, Der p 1 and Der 2) were 116.3 µg/mL in the HDM allergen extract (100000 Japanese Allergy Units [JAU]/mL) and 0.77 µg/mL in the HD 1 : 10. The inhibitory activity (log10 IC50 values) of HD 1 : 10 was 2.389 ± 0.078, indicating the allergenic potency was between 200 and 2000 JAU/mL. Based on regression analysis (R2 >0.99), the allergenic potency of HD 1 : 10 was estimated to be 842 ± 128 JAU/mL. The present study determined the major allergen content of HD extract, which contributes to its allergenic potency. The allergenic potency of HD 1 : 10 was ca. 100-fold less than that of HDM allergen extract.

VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis.

Within the vascular endothelial growth factor (VEGF) family of five subtypes, VEGF165 secreted by endothelial cells has been identified to be the most active and widely distributed factor that plays a vital role in courses of angiogenesis, vascularization and mesenchymal cell differentiation. Hair follicle stem cells (HFSCs) can be harvested from the bulge region of the outer root sheath of the hair follicle and are adult stem cells that have multi-directional differentiation potential. Although the research on differentiation of stem cells (such as fat stem cells and bone marrow mesenchymal stem cells) to the endothelial cells has been extensive, but the various mechanisms and functional forms are unclear. In particular, study on HFSCs' directional differentiation into vascular endothelial cells using VEGF165 has not been reported. In this study, VEGF165 was used as induction factor to induce the differentiation from HFSCs into vascular endothelial cells, and the results showed that Notch signalling pathway might affect the differentiation efficiency of vascular endothelial cells. In addition, the in vivo transplantation experiment provided that HFSCs could promote angiogenesis, and the main function is to accelerate host-derived neovascularization. Therefore, HFSCs could be considered as an ideal cell source for vascular tissue engineering and cell transplantation in the treatment of ischaemic diseases.

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

BACKGROUND: In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. METHODS: The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. RESULTS: The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. CONCLUSIONS: SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time.

Oral administration of ovalbumin after sensitization attenuates symptoms in a mouse model of food allergic enteropathy.

Oral immunotherapy (OIT) is a promising treatment of food allergy. To administer an appropriate oral dose of an allergenic component as OIT to individuals sensitized with a food allergen may prevent inducing food allergic inflammation in them. So we attempted to establish a mouse model to evaluate efficacy for oral administration of food allergen after sensitization. In BALB/c mice sensitized by injecting ovalbumin (OVA) with alum twice, OVA was administered before inducing inflammation by feeding the mice with egg white (EW) diet. Severe inflammatory responses, such as enteropathy, weight loss, IL-4 production, and increase of IgE antibody levels, were suppressed by administration with 4 mg of OVA 7 times before feeding EW diet. OVA administration alone induced a slight Th2 response, but no symptoms. The current study demonstrated that severe food allergic enteropathy could be prevented by pre-administration with appropriate dose of OVA to sensitized mice.

Recent Efficacy of Oblique Lateral Interbody Fusion Combined With Wiltse Approach Pedicle Screw Fixation for Degenerative Single-Level Lumbar Spondylolisthesis.

BACKGROUND: The study aimed to explore the recent efficacy of oblique lateral interbody fusion (OLIF) combined with Wiltse approach pedicle screw fixation in the treatment of single-level degenerative lumbar spondylolisthesis (DLS). METHODS: This is a retrospective study. The study enrolled 54 patients with single-level DLS who were treated at the Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University from May 2018 to June 2020. (OLIF group) 24 cases operated using OLIF combined with Wiltse approach pedicle screw fixation, and (PLIF group) 30 cases operated by PLIF. The primary outcome measures were visual analog scale (VAS) pain scores, Oswestry dysfunction index (ODI), and the lower lumbar spine anterior convexity angle. RESULTS: There were significant differences in VAS (2.63 ± 0.58 vs. 3.57 ± 0.63, P < 0.001) and ODI (9.67 ± 0.92 vs. 10.63 ± 1.40, P < 0.05) between the OLIF group and PLIF group on postoperative 3 days. And there was a significant decrease in VAS (2.63 ± 0.58 vs. 1.08 ± 0.28, P < 0.05) and ODI (3.57 ± 0.63 vs. 1.10 ± 0.31, P < 0.05) in both groups on postoperative 3 days and at 6 months postoperative comparisons. OLIF group showed better intervertebral space height and the lower lumbar spine anterior convexity angle scores on postoperative 3 days and 6 months, the difference was statistically significant(all P < 0.05). CONCLUSIONS: OLIF combined with the Wiltse approach pedicle screw fixation can achieve good short-term clinical results in the treatment of single-level DLS. This surgical approach is less invasive, promotes early functional recovery, shortens hospitalization time, and improves the quality of life.

Treatment of fifth metacarpal neck fracture in adolescents with minimally invasive surgery: percutaneous Kirschner wire fixation versus elastic stable intramedullary nailing.

OBJECTIVE: This retrospective study compared two minimally invasive surgical methods for fifth metacarpal neck fractures in adolescents: percutaneous Kirschner wire (K-wire) fixation and elastic stable intramedullary nailing (ESIN). METHODS: This study involved 42 adolescents aged 11 to 16 years with fifth metacarpal neck fractures treated by either K-wire fixation (n = 20) or ESIN (n = 22). The palmar tilt angle and shortening were compared on radiographs preoperatively and 6 months postoperatively. Total active range of motion (TAM), the visual analogue scale score for pain, and the Disabilities of the Arm, Shoulder and Hand score for upper limb function were recorded at 5 weeks, 3 months, and 6 months postoperatively. RESULTS: The mean TAM was significantly greater in the ESIN than K-wire group at all postoperative time points. The mean external fixation time was 2 weeks longer in the K-wire than ESIN group. One patient in the K-wire group developed infection. There was no statistically significant difference between the two groups in other postoperative outcomes. CONCLUSIONS: ESIN fixation has the advantages of greater stability, better activity, a shorter external fixation time, and a lower infection rate than K-wire fixation in the treatment of fifth metacarpal neck fractures in adolescents.

Association between fibrinogen and bone mineral density in postmenopausal women.

OBJECTIVE: There is very limited of evidence linking fibrinogen and bone mineral density (BMD) in postmenopausal women. Therefore, this study intended to examine the relationship between fibrinogen and total BMD in postmenopausal women. METHODS: This cross-sectional analysis included 2043 postmenopausal women aged 50 years and older from the 1999 to 2002 National Health and Nutrition Examination Survey. The independent variable was fibrinogen and the outcome variable was total BMD. The association between fibrinogen and total BMD in postmenopausal women was examined using multivariate linear regression models, with subgroup analyses stratified by race. Smoothing curve fitting and generalized additive models further analyzed the sample data. RESULTS: In multiple regression models adjusted for potential confounders, fibrinogen was negatively associated with total BMD (model 1: - 0.0002 [- 0.0002, - 0.0001], model 2: - 0.0000 [- 0.0001, - 0.0000], model 3: - 0.0001 [- 0.0001, - 0.0001]). In subgroup analysis stratified by race, fibrinogen levels were negatively associated with total BMD in postmenopausal women, Non-Hispanic Whites, and Mexican Americans. However, in Non-Hispanic Blacks, the correlation between fibrinogen levels and total BMD was not significant. For individuals that identify as Other Races, fibrinogen levels were positively correlated with total BMD. CONCLUSION: Our findings show a negative association between fibrinogen levels and total BMD in most postmenopausal women aged 50 years and older, however, is variable by race. In postmenopausal women, Non-Hispanic Whites and Mexican Americans, relatively high fibrinogen levels may be adverse to bone health.

Association between urinary glyphosate exposure and bone mineral density in adults.

There is very limited evidence linking glyphosate exposure to bone mineral density in adults aged 20 to 59 years in the National Health and Nutrition Examination Survey database. Hence, this study aimed to investigate the correlation between urinary glyphosate concentrations and total bone mineral density (BMD) in adults aged 20 to 59 years. A cross-sectional study was conducted using data from the 2013 to 2016 National Health and Nutrition Examination Survey, which included 594 men (mean age 39.1 years) and 610 women (mean age 40.0 years). In our study, we utilized a weighted multiple regression equation model to investigate the potential correlation between urinary glyphosate concentration and total BMD. Additionally, we conducted a stratified analysis to differentiate between various special populations. Our findings revealed a significant negative association between urinary glyphosate concentration and total BMD across 3 different regression models (Model 1, ß [95% CI]: -0.0160 [-0.0200, -0.0120]; Model 2, ß [95% CI]: -0.0135 [-0.0172, -0.0098]; Model 3, ß [95% CI]: -0.0141 [-0.0178, -0.0104]). However, after stratifying by gender, age, and race, we observed varying conclusions. This study found that urinary glyphosate concentration was negatively associated with total BMD in both men and women when stratified by sex. Additionally, when stratified by age, the negative association was more significant in the 20 to 29 and 50 to 59 year age groups. When stratified by race, a significant negative association was found in races other than Hispanic. Therefore, the impact of glyphosate exposure on BMD should attract more people's attention.

The clinical diagnosis and treatment of the shoulder terrible tetrad: a case report and literature review.

Traumatic anterior dislocation of the shoulder is often associated with anterior glenoid fracture or bankart injury. It can also be associated with rotator cuff injury, humeral greater tuberosity fracture, or brachial plexus injury. However, there are few clinical reports of all the above-mentioned injuries at the same time. We report a case of the left "Shoulder terrible tetrad." After closed reduction of the left shoulder dislocation, we performed one-stage arthroscopic massive rotator cuff repair (Chinese-Way technique) and anchor repair of the bony bankart injury. After 2 years follow-up, the left shoulder function recovered well and the range of motion was satisfactory. A detailed physical examination and electromyography (EMG) examination should be performed in time to avoid misdiagnosis and missed diagnosis, when the clinical manifestation of brachial plexus nerve injury appears after shoulder dislocation. The repairable rotator cuffs tears and bankart injuries can be repaired under shoulder arthroscopy in one stage.

Association between the ratio of serum creatinine to cystatin C and bone mineral density in middle-aged and older adults: a cross-sectional study from NHANES database.

OBJECTIVE: To investigate the association between creatinine to cystatin C ratio (CCR) and bone mineral density (BMD) in middle-aged and older adults. METHODS: This cross-sectional study investigated participants aged 50-85, using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2002. The correlation between CCR and total BMD was assessed by multivariate linear regression models, using stratified analysis by age, sex and race (Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, and other race) to distinguish various special populations. RESULTS: Among 2992 patients, multiple regression models revealed a significant positive correlation between CCR and total BMD: model 1, 0.030 (95% confidence interval [CI] 0.029, 0.031); model 2, 0.009 (95% CI 0.008, 0.010); model 3, 0.010 (95% CI 0.009, 0.013). After controlling for all covariates, a positive correlation was observed between CCR and total BMD in both men and women, and was further strengthened in older age groups. When stratifying by race, the positive correlation was most significant among 'other Hispanic' participants; there was no significant correlation among those of 'other race'. CONCLUSIONS: A positive correlation was demonstrated between CCR and total BMD in middle-aged and older adults aged 50-85 years, with the most significant positive correlation in the older 'other Hispanic' population. No significant correlation was observed among participants of 'other race'.

Association between creatine phosphokinase level within normal range and bone mineral density in adolescents.

Currently, it is unclear whether creatine phosphokinase (CPK) affects bone mineral density (BMD) in adolescents. We sought to clarify the relationship between CPK and total BMD in adolescents aged 12 to 19 years within normal values by conducting this study. A cross-sectional study was conducted using the 2011 to 2018 National Health and Nutrition Survey data to examine 1188 males (average age, 15.2 years) and 1629 females (average age, 15.4 years). In this study, CPK was the independent variable and total BMD was the outcome variable. In addition to using multivariate linear regression models, subgroup analyses were also conducted in order to examine the relationship between CPK levels and total BMD within normal ranges. Significant positive association was observed between the CPK levels and total BMD in adolescents (model 1: 0.0003 [0.0002, 0.0004], model 2: 0.0004 [0.0003, 0.0005] and model 3: 0.0004 [0.0003, 0.0004]). After adjusting for age, gender, race/ethnicity, body mass index, dietary protein intake, dietary protein intake, dietary fiber intake, poverty to income ratio, physical activities, total cholesterol, total protein, blood urea nitrogen, phosphorus, and serum calcium, CPK levels remained significantly associated with BMD (regression coefficients for quartiles 2 to 4 vs quartile1 were 0.0002, 0.0072, and 0.0154, respectively; P for trend <.001). The association was positive even when stratified by age, gender, and race. Further, adolescents aged 16 to 19 years were more likely to report positive relationships than adolescents aged 12 to 15 years. And the phase relationship between total BMD and CPK was further enhanced in boys. The results of our study show that CPK levels within the normal range are positively associated with total BMD in adolescents aged 12 to 19 years. Additionally, CPK may be a potential biomarker of bone health among adolescents.

[Clinical outcomes of reverse shoulder arthroplasty for the treatment of failed fixation of proximal humeral fracrtures in the elderly patients].

OBJECTIVE: To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients. METHODS: A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded. RESULTS: All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications. CONCLUSION: Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.

WISP2 downregulation inhibits the osteogenic differentiation of BMSCs in congenital scoliosis by regulating Wnt/ß-catenin pathway.

OBJECTIVES: Bone marrow mesenchymal stem cells (BMSCs) are instrumental in bone development, metabolism, and marrow microenvironment homeostasis. Despite this, the relevant effects and mechanisms of BMSCs on congenital scoliosis (CS) remain undefined. Herein, it becomes our focus to reveal the corresponding effects and mechanisms implicated. METHODS: BMSCs from CS patients (hereafter referred as CS-BMSCs) and healthy donors (NC-BMSCs) were observed and identified. Differentially expressed genes in BMSCs were analyzed utilizing scRNA-seq and RNA-seq profiles. The multi-differentiation potential of BMSCs following the transfection or infection was evaluated. The expression levels of factors related to osteogenic differentiation and Wnt/ß-catenin pathway were further determined as appropriate. RESULTS: A decreased osteogenic differentiation ability was shown in CS-BMSCs. Both the proportion of LEPR+ BMSCs and the expression level of WNT1-inducible-signaling pathway protein 2 (WISP2) were decreased in CS-BMSCs. WISP2 knockdown suppressed the osteogenic differentiation of NC-BMSCs, while WISP2 overexpression facilitated the osteogenesis of CS-BMSCs via acting on the Wnt/ß-catenin pathway. CONCLUSIONS: Our study collectively indicates WISP2 knockdown blocks the osteogenic differentiation of BMSCs in CS by regulating Wnt/ß-catenin signaling, thus providing new insights into the aetiology of CS.