Exploring the chondroprotective effect of Chaenomeles speciosa on Glucose-6-Phosphate Isomerase model mice using an integrated approach of network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Chaenomeles speciosa (CSP) (Chinese Pinyin: mugua) is a medicinal and food herb that has long been used as a folk medicine for rheumatic diseases, yet its bioactive components and therapeutic mechanisms are not clear. AIM OF THE STUDY: Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action. MATERIALS AND METHODS: In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA. RESULTS: Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1ß, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1ß, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction. CONCLUSION: This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA.

Prominent Size Effects without a Depolarization Field Observed in Ultrathin Ferroelectric Oxide Membranes.

The increasing miniaturization of electronics requires a better understanding of material properties at the nanoscale. Many studies have shown that there is a ferroelectric size limit in oxides, below which the ferroelectricity will be strongly suppressed due to the depolarization field, and whether such a limit still exists in the absence of the depolarization field remains unclear. Here, by applying uniaxial strain, we obtain pure in-plane polarized ferroelectricity in ultrathin SrTiO_{3} membranes, providing a clean system with high tunability to explore ferroelectric size effects especially the thickness-dependent ferroelectric instability with no depolarization field. Surprisingly, the domain size, ferroelectric transition temperature, and critical strain for room-temperature ferroelectricity all exhibit significant thickness dependence. These results indicate that the stability of ferroelectricity is suppressed (enhanced) by increasing the surface or bulk ratio (strain), which can be explained by considering the thickness-dependent dipole-dipole interactions within the transverse Ising model. Our study provides new insights into ferroelectric size effects and sheds light on the applications of ferroelectric thin films in nanoelectronics.

[Analysis of the curative effect of triple surgery under endoscope in the treatment of intractable heel pain].

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION: Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.

[Research progress of lower limb alignment correction and prosthesis position angle in unicompartmental knee arthroplasty].

The angle between the lower extremity force line and the position of the unicondylar prosthesis is an important factor affecting the long-term survival and rate clinical outcome of the unicondylar replacement prostheses. Insufficient lower limb alignment will accelerate the wear of prosthesis and reduce the survival rate of prosthesis. Excessive lower limb alignment will accelerate the progress of contralateral interventricular arthritis. It is generally believed that the lower limb force line should be corrected in mild varus after unicompartmental knee arthroplasty. However, some scholars believe that the lower limb alignment has no effect on the functional score and prosthesis survival rate after unicompartmental knee arthroplasty. The poor position of femoral and tibial prosthesis will cause unexplained pain and even prosthesis wear, but the optimal position of femoral and tibial prosthesis is controversial. It is generally believed that the posterior tibial slope should be corrected in the range of 3° to 7° in unicompartmental knee arthroplasty, but some scholars believe that excessive change of posterior tibial slope will also affect the balance of knee joint space and knee joint range of motion. This study shows that the correction of lower limb alignment to mild varus is still the best lower limb alignment for unicompartmental knee arthroplasty. The best position of femoral and tibial prosthesis needs to be confirmed by further biomechanical research. The correction of tposterior tibial slope should be changed according to the specific original dissection angle of patients before operation.

The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis.

Achilles tendon healing (ATH) remains an unanswered question in the field of sports medicine because it does not produce tissue with homology to the previously uninjured tissue. Oestrogen receptor ß (ERß) is involved in the injury and repair processes of tendons. Our previous study confirmed that ERß plays a role in the early stage of ATH by affecting adipogenesis, but its role in extracellular matrix (ECM) remodelling is unknown. We established a 4-week Achilles tendon repair model to investigate the mechanism through which ERß affects ATH at the very beginning of ECM remodelling phase. In vitro studies were performed using tendon-derived stem cells (TDSCs) due to their promising role in tendon healing. Behavioural and biomechanical tests revealed that ERß-deficient mice exhibit weaker mobility and inferior biomechanical properties, and immunofluorescence staining and qRT-PCR showed that these mice exhibited an erroneous ECM composition, as mainly characterized by decreased collagen type I (Col I) deposition. The changes in gene expression profiles between ERß-knockout and WT mice at 1 week were analysed by RNA sequencing to identify factors affecting Col I deposition. The results highlighted the IRF5-CCL3 axis, and this finding was verified with CCL3-treated TDSCs. These findings revealed that ERß regulates Col I deposition during ATH via the IRF5-CCL3 axis.