Greater pelvic obliquity in adolescent idiopathic scoliosis combined with hip dysplasia.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a spinal deformity that affects adolescents and poses a challenging public health problem. Compared to the general population, adolescents with AIS have a higher prevalence of hip dysplasia. However, the mechanisms underlying the impact of hip dysplasia on the coronal balance of the spine remain poorly understood. We hypothesized that the combination of AIS with hip dysplasia would exacerbate coronal imbalance. METHODS: We retrospectively analyzed the medical records and radiographs of adolescents diagnosed with AIS between 2015 and 2020. Participants were divided into two groups: those with hip dysplasia and those without. We recorded parameters related to the coronal deformity of the spine, sacral and pelvic obliquity, and center edge angle (CEA). We investigated differences in these parameters in those with and without hip dysplasia and analyzed their relationships in those with combined AIS and hip dysplasia. RESULTS: A total of 103 adolescents were included, 36 with hip dysplasia and 67 without. Those with hip dysplasia had significantly higher sacroiliac discrepancy (SID) compared to those without (t = - 2.438, P = 0.017). In adolescents with hip dysplasia, only iliac obliquity angle (IOA) was significantly correlated with SID (r = - 0.803, P < 0.001), with a linear relationship between them (r2 = 0.645, P < 0.001). CONCLUSIONS: The incidence of hip dysplasia is higher in the AIS population. In adolescents with combined AIS and hip dysplasia, pelvic obliquity is greater, potentially contributing to the increased prevalence of low back pain.

Corrigendum: Biomechanical outcomes of superior capsular reconstruction for irreparable rotator cuff tears by different graft materials-a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fsurg.2022.939096.].

Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy.

Chemodynamic therapy (CDT)-activated apoptosis is a potential anticancer strategy. However, CDT encounters a bottleneck in clinical translation due to its serious side effects and low efficacy. Here, we first reveal that surface engineering of ginsenoside Rg3 dramatically alters the organ distribution and tumor enrichment of systematically administered nanocatalysts using the orthotopic pancreatic tumor model while avoiding toxicity and increasing efficacy in vivo to address the key and universal toxicity problems encountered in nanomedicine. Compared with nanocatalysts alone, Rg3-sheltered dynamic nanocatalysts form hydrophilic nanoclusters, prolonging their circulation lifespan in the blood, protecting the internal nanocatalysts from leakage while allowing their specific release at the tumor site. Moreover, the nanoclusters provide a drug-loading platform for Rg3 so that more Rg3 reaches the tumor site to achieve obvious synergistic effect with nanocatalysts. Rg3-sheltered dynamic nanocatalysts can simultaneously activate ferroptosis and apoptosis to significantly improve anticancer efficacy. Systematic administration of ginsenoside Rg3-sheltered nanocatalysts inhibited 86.6% of tumor growth without toxicity and prolonged the survival time of mice. This study provides a promising approach of nanomedicine with high biosafety and a new outlook for catalytic ferroptosis-apoptosis combined antitumor therapies. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has limited clinical efficacy in cancer. In this study, we developed Rg3-sheltered dynamic nanocatalysts, which could simultaneously activate ferroptosis based on CDT-activated apoptosis, and ultimately form a combined therapy of ferroptosis-apoptosis to kill tumors. Studies have shown that the nanocatalysts after Rg3 surface engineering dramatically alters the pharmacokinetics and organ distribution of the nanocatalysts after being systematically administered, resulting in avoiding the toxicity of the nanocatalysts. Nanocatalysts also act as a drug-loading platform, guiding more Rg3 into the tumor site. This study emphasizes that nanocatalysts after Rg3 surface engineering improve the safety and effectiveness of ferroptosis-apoptosis combined therapy, providing an effective idea for clinical practices.

Biomechanical outcomes of superior capsular reconstruction for irreparable rotator cuff tears by different graft materials-a systematic review and meta-analysis.

Background: Irreparable rotator cuff tears (IRCT) are defined as defects that cannot be repaired due to tendon retraction, fat infiltration, or muscle atrophy. One surgical remedy for IRCT is superior capsular reconstruction (SCR), which fixes graft materials between the larger tuberosity and the superior glenoid. Patients and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria were followed for conducting the systematic review and meta-analysis. From their inception until February 25, 2022, Pubmed, Embase, and Cochrane Library's electronic databases were searched. Studies using cadavers on SCR for IRCT were also included. The humeral head's superior translation and subacromial peak contact pressure were the primary outcomes. The humeral head's anteroposterior translation, the kind of graft material used, its size, and the deltoid load were the secondary outcomes. Results: After eliminating duplicates from the search results, 1,443 unique articles remained, and 20 papers were finally included in the quantitative research. In 14 investigations, the enhanced superior translation of the humeral head was documented in IRCTs. In 13 studies, a considerable improvement following SCR was found, especially when using fascia lata (FL), which could achieve more translation restraints than human dermal allograft (HDA) and long head of bicep tendon (LHBT). Six investigations reported a subacromial peak contact pressure increase in IRCTs, which could be rectified by SCR, and these studies found a substantial increase in this pressure. The results of the reduction in subacromial peak contact pressure remained consistent regardless of the graft material utilized for SCR. While there was a statistically significant difference in the change of graft material length between FL and HDA, the change in graft material thickness between FL and HDA was not significant. The humeral head's anterior-posterior translation was rising in IRCTs and could be returned to its original state with SCR. In five investigations, IRCTs caused a significant increase in deltoid force. Furthermore, only one study showed that SCR significantly decreased deltoid force. Conclusion: With IRCT, SCR might significantly decrease the glenohumeral joint's superior and anterior-posterior stability. Despite the risks for donor-site morbidity and the longer recovery time, FL is still the best current option for SCR.

An early clinical comparative study on total knee arthroplasty with kinematic alignment using specific instruments versus mechanical alignment in varus knees.

Background: The kinematic alignment technique, as one of the alignment options for total knee arthroplasty, has attracted increasing attention from orthopedic surgeons and has been increasingly performed in the most populous countries in the world. The purpose of this study is to explore and compare the early clinical outcomes of total knee arthroplasty with KA using specific instruments vs. mechanical alignment in our nation. Methods: A retrospective analysis was performed on patients who underwent unilateral total knee arthroplasty for knee osteoarthritis with varus deformity. Depending on the alignment method, patients were divided into a kinematically aligned total knee arthroplasty (KA-TKA) group and a mechanically aligned total knee arthroplasty (MA-TKA) group. The hip-knee-ankle (HKA) angle before and after surgery, the knee joint clinical score (KS-C), the knee joint functional score (KS-F) and the forgotten joint score (FJS) at 3 months and 2 years after surgery were recorded and statistically analyzed. Results: A total of 126 patients were enrolled, including 65 in the KA-TKA group and 61 in the MA-TKA group. The mean follow-up period was 30.8 months. The postoperative HKA angle was not significantly different at the 2-year follow-up between the two groups (P > 0.05). The KS-C, KS-F and FJS scores in the KA-TKA group were higher than those in the MA-TKA group at 3 months after surgery, and the difference was statistically significant (P < 0.05). At the 2-year follow-up, the KS-C, KS-F and FJS scores in the KA-TKA group were higher than those in the MA-TKA group, and the difference in the KS-C and FJS scores was statistically significant (P < 0.05). Conclusion: Patients who underwent KA-TKA had a postoperative lower limb alignment similar to that of those who underwent MA-TKA. The clinical outcomes of KA-TKA were superior to those of MA-TKA in terms of clinical performance, knee function and subjective sensation up to 2 years after surgery.

Prussian Blue/Calcium Peroxide Nanocomposites-Mediated Tumor Cell Iron Mineralization for Treatment of Experimental Lung Adenocarcinoma.

Current lung cancer diagnosis methods encounter delayed visual confirmation of tumor foci and low-resolution metrics in imaging findings, which delays the early treatment of tumors. Here, we developed a potent lung cancer imaging and treatment strategy centered around a nanotransformational concept of tumor iron mineralization in situ, which employs Prussian blue/calcium peroxide nanocomposites as a precursor. The resultant iron mineralization in tumor cells greatly facilitates the early and differential diagnosis of lung carcinoma from benign nodules via medical imaging, meanwhile introducing oxidative stress to activate the cellular apoptosis and ferroptosis pathways, resulting in inhibition of the malignant behavior of tumor cells. Tumor-microenvironment-triggered iron mineralization enables integration of the detection and prevention of tumor metastasis at its early stages with no assistance of toxic drugs, which offers a potential solution for the precise management of lung cancer with ideal outcomes.

[Effectiveness comparison of partial versus intact posterior cruciate ligament-retaining in total knee arthroplasty with cruciate-retaining prosthesis].

OBJECTIVE: To compare the effectiveness of partial versus intact posterior cruciate ligament (PCL)-retaining in total knee arthroplasty (TKA) with cruciate-retaining (CR) prosthesis. METHODS: A total of 200 patients with osteoarthritis, who met the selection criteria and proposed unilateral TKA with CR prosthesis, were included in the study and randomly assigned into two groups ( n=100). The patients were treated with intact retention of the double bundles of PCL in intact group and with partial resection of the anterior lateral bundle of PCL and the anterior bone island at the time of intraoperative tibial osteotomy in partial group. Patients with lost follow-up and re-fracture were excluded, and 84 cases in partial group and 88 cases in intact group were included in the final study. There was no significant difference between the two groups ( P>0.05) in terms of gender, age, body mass index, course and grade of osteoarthritis, preoperative varus deformity of knee joint, flexion contracture, range of motion, clinical and functional scores of Knee Society Score (KSS). The operation time, wound drainage volume during 24 hours after operation, visual analogue scale (VAS) score at 24 hours after operation, range of motion of knee joint, clinical and functional scores of KSS, and the anteroposterior displacement of knee joint at 30° and 90° flexion positions were compared between the two groups. RESULTS: There was no significant difference between the two groups in operation time, wound drainage volume during 24 hours after operation, and VAS score at 24 hours after operation ( P>0.05). Patients in both groups were followed up after operation. The follow-up time was 25-40 months (mean, 30.2 months) in intact group and 24-40 months (mean, 31.8 months) in partial group. There was no significant difference in the range of motion and clinical scores of KSS between the two groups at 6, 12, and 24 months after operation ( P>0.05). The functional scores of KSS were significantly higher in intact group than in partial group ( P<0.05). There was no significant difference between the two groups in the anteroposterior displacement of knee joints at 30° flexion position at 6, 12, and 24 months after operation ( P>0.05). When the knee was at 90° flexion position, there was no significant difference between the two groups at 6 and 12 months after operation ( P>0.05), but the intact group was significantly smaller than partial group at 24 months after operation ( P<0.05). Postoperative incision continued exudation in 4 patients (2 cases of partial group and 2 cases of intact group), and incision debridement in 2 patients (1 case of partial group and 1 case of intact group). No prosthesis loosening, excessive wear, or dislocation of gasket was found during follow-up. CONCLUSION: The double bundle of PCL plays an equally important role in maintaining the stability of the knee joint, and the integrity of PCL should be kept as much as possible when TKA is performed with CR prosthesis.

The synthesis of a nanodrug using metal-based nanozymes conjugated with ginsenoside Rg3 for pancreatic cancer therapy.

Nanozymes have limited applications in clinical practice due to issues relating to their safety, stability, biocompatibility, and relatively low catalytic activity in the tumor microenvironment (TME) in vivo. Herein, we report a synergistic enhancement strategy involving the conjugation of metal-based nanozymes (Fe@Fe3O4) with natural bioactive organic molecules (ginsenoside Rg3) to establish a new nanodrug. Importantly, this metal-organic nanocomposite drug ensured the stability and biosafety of the nanozyme cores and the cellular uptake efficiency of the whole nanodrug entity. This nanodrug is based on integrating the biological characteristics and intrinsic physicochemical properties of bionics. The glycoside chain of Rg3 forms a hydrophilic layer on the outermost layer of the nanodrug to improve the biocompatibility and pharmacokinetics. Additionally, Rg3 can activate apoptosis and optimize the activity and status of normal cells. Internal nanozymes enter the TME and release Fe3+ and Fe2+, and the central metal Fe(0) continuously generates highly active Fe2+ under the conditions of the TME and in the presence of Fe3+, maintaining the catalytic activity. Therefore, these nanozymes can effectively produce reactive oxygen species and oxygen in the TME, thereby promoting the apoptosis of cancer cells. Thus, we propose the use of a new type of metal-organic nanocomposite material as a synergistic strategy against cancer.

Synthesis of nanomedicine hydrogel microcapsules by droplet microfluidic process and their pH and temperature dependent release.

Chitosan and alginate hydrogels are attractive because they are highly biocompatible and suitable for developing nanomedicine microcapsules. Here we fabricated a polydimethylsiloxane-based droplet microfluidic reactor to synthesize nanomedicine hydrogel microcapsules using Au@CoFeB-Rg3 as a nanomedicine model and a mixture of sodium alginate and PEG-g-chitosan crosslinked by genipin as a hydrogel model. The release kinetics of nanomedicines from the hydrogel were evaluated by simulating the pH and temperature of the digestive tract during drug transport and those of the target pathological cell microenvironment. Their pH and temperature-dependent release kinetics were studied by measuring the mass loss of small pieces of thin films formed by the nanomedicine-encapsulating hydrogels in buffers of pH 1.2, 7.4, and 5.5, which replicate the pH of the stomach, gut and blood, and cancer microenvironment, respectively, at 20 °C and 37 °C, corresponding to the storage temperature of hydrogels before use and normal body temperature. Interestingly, nanomedicine-encapsulating hydrogels can undergo rapid decomposition at pH 5.5 and are relatively stable at pH 7.4 at 37 °C, which are desirable qualities for drug delivery, controlled release, and residue elimination after achieving target effects. These results indicate that the designed nanomedicine hydrogel microcapsule system is suitable for oral administration.

Nanoparticle Conjugation of Ginsenoside Rg3 Inhibits Hepatocellular Carcinoma Development and Metastasis.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe3 O4 nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine-induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC-induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty-nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor-dominant metabolomics. NpRg3 administration decreases 3-indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.

Protective Effects of Prunasin A against the Differentiation of Osteoclasts and Destruction of Cartilage via the Receptor Activator of Nuclear Factor-Kappa-Β Ligand/Mitogen-Activated Protein Kinase/Osteoprotegerin Pathway in a Rat Model of Arthritis.

The present study evaluated the protective effects of pseurotin A against inflammation and the destruction of cartilage in a rat model of rheumatoid arthritis (RA). RA was induced by intradermal injections of Freund's complete adjuvant (1 mg/mL), and the treatment with pseurotin A (50 and 100 mg/kg, p.o.) was administered over 1 week. The effects of pseurotin A were assessed by estimating hind paw volume (HPV) and determining the levels of inflammatory mediators in the serum and synovial fluid of collagen-induced arthritis (CIA)-induced RA rats. Western blot and histopathological assays were performed to assess changes in synovial tissues. Additionally, in vitro analyses of receptor activator of nuclear factor-kappa-Β ligand (RANKL)-stimulated RAW264.7 cells treated with pseurotin A at different concentrations (1, 10, and 100 µg/mL) were conducted to assess the effects of pseurotin A on apoptosis ratio, real-time polymerase chain reaction data, and tartrate-resistant acid phosphatase staining. Compared to the RA group, treatment with pseurotin A significantly decreased HPV and reduced the levels of inflammatory mediators in the synovial fluid and blood. Additionally, pseurotin A ameliorated the protein expressions of osteoprotegerin, nuclear factor of activated T-cells, nuclear factor-kappa beta (NF-κB), IκBα, extracellular signal regulated kinase, and P38 as well as histopathological changes in the synovial tissue of CIA-induced RA rats. The in vitro findings revealed that pseurotin A treatment did not alter the apoptosis ratio in RANKL-stimulated RAW264.7 cells but significantly reduced the mRNA expressions of calcitonin receptor, NF-κB, and matrix metallopeptidase-9. The present findings suggest that pseurotin A ameliorated the differentiation of osteoclasts and the destruction of cartilage in RA rats via regulation of the mitogen-activated protein kinase/RANKL/NF-kB pathway.

Synthesis of nanomedicines by nanohybrids conjugating ginsenosides with auto-targeting and enhanced MRI contrast for liver cancer therapy.

A new methodology has been developed with conjugating nanoparticles (NPs) with an active ingredient of Chinese herbs for nanomedicines with auto-targeting and enhanced magnetic resonance imaging (MRI) for liver cancer therapy. Fe@Fe3O4 NPs are first synthesized via the programed microfluidic process, whose surfaces are first modified with -NH2 groups using a silane coupling technique that uses (3-aminopropyl)trimethoxysilane (APTMS) as the coupling reagent and are subsequently activated by the bifunctional amine-active cross-linker [e.g. disuccinimidyl suberate (DSS)]. The model medicines of ginsenosides pre-activated by APTMS are further cross-linked with activated NPs, forming the desired nanomedicines (Nano-Fe-GSS). Sizes and structures of Fe@Fe3O4 NPs were characterized by transmission electron microscopy and X-ray diffraction, revealing that their core-shell structures consist of amorphous boron doped Fe cores and partial crystalline Fe3O4 shells. The accomplishment of coupling reactions in the final nanomedicines is confirmed by the characterization of the composition of NPs and Nano-Fe-GSS via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. The nanoparticles' effects as MRI contrast agents are further investigated by comparing the T2 weighted spin echo imaging (T2WI) in livers before and after intravenous injection and intragastric administration of nanomedicines. The results indicate that these nanomedicines possess enhanced MRI effects. Investigation of the toxicity and metabolism of Nano-Fe-GSS suggests that they are safe to related vital organs. The results provide an efficient alternative route to synthesize desired multi-functional nanomedicines based on NPs and the active ingredients of Chinese herbs, which can promote their potential synergistic effects in anti-tumor therapy.