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.

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.

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'.

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 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.

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.

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.

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.

[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.

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.

A novel approach for the treatment of Jacob II and III fractures of the lateral humeral condyle in children: Percutaneous Kirschner wire fixation with ultrasound localization.

This research investigated the effectiveness of percutaneous Kirschner wire fixation in children with Jacob II and III lateral humeral condyle fractures. 28 children with Jacob II and III lateral humeral condyle fractures were treated with percutaneous Kirschner wire fixation under ultrasound localization, followed by cast immobilization for 4-5 weeks at our institution from January 2018 to April 2022. X-rays were evaluated on the first postoperative day to assess fracture reduction and Kirschner wire fixation. After 2 and 4 weeks, x-rays were taken to assess fracture healing and the presence of discomfort and infection was evaluated. After confirming fracture healing and callus formation, the cast and Kirschner wire were removed. Rehabilitation exercises were conducted following removal to restore elbow function. At the last follow-up, most results were excellent (n = 25) and good (n = 3) according to Flynn's criteria. Moreover, according to the Mayo Elbow Functional Score Scale (MEPS), all 28 children had excellent scores, with no significant difference in MEPS scores between the lesion and healthy sides (t = 1.533, p > 0.05). The present study substantiated that our novel approach is more convenient and effective, brings less trauma and complications and no radiation and deserves clinical promotion.

Study on the mechanism of cadmium chloride pollution accelerating skin tissue metabolism disorder, aging and inhibiting hair regeneration.

Drinking water contaminated by Cd2+ is one of the main pathways for Cd to enter the body. The skin barrier is destroyed when the skin is contaminated by environmental Cd2+, however, the detailed mechanism by which Cd2+ induces skin metabolic disorder, and senescence and affects hair regeneration is not completely understood. In this study, 18 C57BL/6 mice were randomly divided into a Control group, a Low-dose group, and a High-dose group with 6 mice in each group, and intragastrically administered with different concentrations of cadmium chloride once a day, respectively. After 1 month of intervention, the skin tissues on the back of mice were collected for non-targeted metabolomics analysis, and the related proteins were detected by immunofluorescence assay. Non-targeted metabolomics analysis result showed that compared with the Control group, there were 29 different metabolites, mainly including lysophospholipids, fatty acids, and bile acids, in the Low-dose group, and 39 differential metabolites in the High-dose group, in addition to the above compounds, there were more amino acid compounds, and most of the metabolites had a reduced response after administration. Immunofluorescence assay result showed that the higher the concentration of cadmium chloride led to the more obvious the proliferation inhibition and apoptosis promotion effects of skin cells, and the more significant damage to hair follicle stem cells. Thus, our findings demonstrate that cadmium chloride pollution can accelerate skin metabolism disorder, and aging and impair hair regeneration.

α-Chaconine Facilitates Chondrocyte Pyroptosis and Nerve Ingrowth to Aggravate Osteoarthritis Progression by Activating NF-κB Signaling.

Background: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure. Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression. Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 µM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1ß, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence. Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation. Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.

Another new attempt to repair finger pulp defects: retrograde island flap bridge transfer of the adjacent phalangeal artery combined with vascular pedicle tubular skin grafting.

This study investigated the surgical method and therapeutic effect of retrograde island flap bridge transfer of the adjacent phalangeal artery combined with vascular pedicle tubular skin grafting to repair finger pulp defects. From June 2008 to May 2020, 21 fingers (19 patients) were repaired using this method. The postoperative flap survival rate and complications, and the clinical effect, were evaluated. All flaps survived, and all patients were followed-up for 12 to 46 months. The static two-point discrimination (2PD) was 7 to 11 mm, no apparent complications were observed in the donor area and the McIndoe cold intolerance symptom severity (CISS) scores indicated mild severity. The Michigan hand outcome questionnaire (MHQ) indicated that all patients were satisfied with their overall hand appearance and function. Results were excellent in 15 cases and good in 4 cases, according to the Dargan function evaluation (DFE). It is safe and effective to repair finger pulp defects with a retrograde island flap bridge transfer of the adjacent phalangeal artery combined with vascular pedicle tubular skin grafting. This skin flap has the advantages of simple severing, good texture and concealed donor area, which is convenient for early postoperative functional exercise of the finger.

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.

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.

PURPOSE: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. METHODS: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. RESULTS: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1ß, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1ß, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. CONCLUSION: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

Efficacy and Safety of Wenbu Zhibi Granule in Patients with Ankylosing Spondylitis: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

Background. Ankylosing spondylitis (AS) is a chronic disease in which the column is the main lesion. It is caused by a combination of genetic and environmental factors, mainly involving the axial skeleton, resulting in column rigidity and difficulty in movement, and there may be different degrees of eye, lung, cardiovascular, kidney, and other organ damage. Long-term treatment lacks in ankylosing spondylitis. Wenbu Zhibi granule (WZG) is a prescription handed down from the history of Chinese medicine for thousands of years, which is used to treat the pain of patients with AS and to prevent the further development of the disease. However, there is no scientific evidence based on clinical trials to evaluate the efficacy and safety of WZG for ankylosing spondylitis. Methods/Design. We will conduct a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the WZG in the treatment of AS. We will randomly assign 100 patients with active AS to two groups, treated for 16 weeks. The primary efficacy endpoint is the proportion of subjects who reached 40% improvement criteria proposed by Assessment of SpondyloArthritis International Society (ASAS40) at 16 weeks from baseline, the secondary efficacy endpoint includes ASAS20 response rate, ASAS partial remission response rate, 5/6 improvement criteria proposed by ASAS (ASAS5/6) response rate, and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), linear Bath Ankylosing Spondylitis Metrology Index (BASMI), ankylosing spondylitis quality of life (ASQoL). In addition, the time points will be set as baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks, and 48 weeks. Discussion. The results of this study will elucidate the efficacy and safety of WZG and provide an appropriate treatment option for patients with AS. Trial registration: ClinicalTrials.gov ID: https://clinicaltrials.gov/ct2/show/ChiCTR2000041010. (Chinese Clinical Trail Registry, Registered 16 December 2020, http://www.chictr.org.cn).