Imaging anatomy study related to unilateral biportal endoscopic lumbar spine surgery.

PURPOSE: To provide lumbar spine anatomical parameters relevant to the UBE technique and explore their intraoperative application. METHODS: CT imaging data processed by Mimics for parametric measurements, including laminar abduction angle (LAA), laminar slope angle (LSA), minimum laminar height (MLH), distance between the inferior margin of the lamina and attachment of the ligamentum flavum onto the cephalad lamina (DLL), distance between the initial point and the middle of the articular process (DIA), and distance from the inferior margin of the lamina to the inferior border of the vertebral body (DLV), and were manually measured. RESULTS: LAA and DIA gradually increase from L1 to L5. At L1, the DIA is approximately the length of 2 drill bits with a diameter of 3 mm (male: 7.77 ± 1.39 mm, female: 7.22 ± 1.09 mm), while at L5, it can reach the length of 4-5 drill bits (male: 14.96 ± 2.24 mm, female: 13.67 ± 2.33 mm). MLH, DLL, and DLV reach their maximum values at the L3 and decrease toward the cranial and caudal ends. The DLL is smallest at L5 (male: 9.58 ± 1.90 mm, female: 9.38 ± 2.14 mm), equivalent to the length of 3 drill bits, while the DLL at L3 is the length of 4-5 drill bits (male: 14.17 ± 2.13 mm, female: 14.01 ± 2.07 mm). CONCLUSION: Referring to the drill diameter during surgery can mark the extent of laminotomy. The characteristics of vertebral plate angles at different lumbar levels can provide references for preoperative incision design.

First Report of 16SrII Group Related Phytoplasma Associated with Witches'-broom Disease on Cowpea (Vigna unguiculata) in Hainan Province, China.

Cowpea (Vigna unguiculata L.), a significant vegetable crop in China, holds particular prominence in the tropical island of Hainan. This region serves as the primary production area for the winter cultivation of cowpea. Phytoplasmas are an idiopathic parasitic pathogen and cannot be cultured in vitro. It is mainly transmitted by the insect vectors with the piercing and sucking mouthparts, such as leafhoppers, plant hoppers, and psyllids. (Kumari et al. 2019). On September 11, 2023, typical characteristics of phytoplasma diseases on cowpeas were observed in the experimental base of Hainan Academy of Agricultural Sciences (20°0'38.6964″N, 110°21'35.4024″E, Haikou City, Hainan Province, China), including reduced leaf size, chlorosis, and the development of broom-like branch deformities reminiscent, as depicted in Figure 1. At the same time, we found a large number of leafhoppers near the diseased plants, and we speculated that leafhoppers are the insect carriers that spread the disease. Following an on-site investigation, it was determined that the disease incidence ranges from 10% to 15%, leading to a consequential decrease of about 10% in yield, which is a potential disease that seriously threatens the cowpea industry in Hainan. Ten disease and healthy samples were meticulously collected and subsequently preserved at -80°C within the laboratory refrigerator. Three disease samples denoted as HNNKY-1, HNNKY-2, and HNNKY-3, were randomly chosen, and total DNA extraction was carried out employing the NuClean Plant Genomic DNA Kit (CWBIO, Taizhou, China), while three healthy samples were randomly selected as control. The 16S rRNA gene was amplified by PCR using the primer pairs P1/P7 (Schneider et al. 1995) and R16F2n / R16R2 (Lee et al. 1993) and the secA gene was amplified by PCR using the primer pairs secAfor1/secArev3 (Hodgetts et al. 2008). After agarose gel electrophoresis analysis, no DNA fragments were observed in the healthy leaf samples, whereas all three disease samples yielded amplification products. The PCR products were subsequently sequenced by Hainan Nanshan Biotech Co., Ltd., Haikou, China. After sequence analysis, it was found that the 16S rRNA gene and secA gene sequences HNNKY-1, HNNKY-2, and HNNKY-3 were identical to each other. We selected two gene sequences of strain HNNKY-3 to submission to the GenBank database, The length of the 16S rRNA gene sequence is 1193 base pairs, identified by the accession number OR666421, while the secA gene sequence is 825 base pairs in length, associated with the accession number OR661282. The phytoplasma strain HNNKY-3 was named 'Vigna unguiculata' witches'-broom phytoplasma. A BLAST analysis of the 16S rRNA gene revealed that strain HNNKY-3 displayed a 100% sequence match with 'Emilia sonchifolia' witches'-broom phytoplasma (MT420682), Peanut witches'-broom phytoplasma (OR239773), and 'Raphanus sativus' witches'-broom phytoplasma (OK491387). All of these phytoplasmas were classified within the 16SrII group. Based on the BLAST analysis of partial secA gene sequences, it was discerned that sequence homogeneity ranged from 99.27% to 99.74% among the studied sequences. These sequences were collectively classified as members of the 16SrII group. In addition, a phylogenetic tree was constructed by MEGA 11 (version 11.0.13) based on the 16Sr RNA gene and secA gene by the neighbor-joining method (Tamura et al. 2004). The results demonstrated the clustering of HNNKY-3 phytoplasma strains within the 16SrII group, as illustrated in Figures 2 and 3. A virtual RFLP analysis based on the 16S rRNA gene fragment of HNNKY-3 was conducted using the interactive online phytoplasma classification tool, iPhyClassifier (Zhao et al. 2009). The results indicated that the phytoplasma strain was the same as the reference pattern of the onion yellows phytoplasma of 16SrII-A (GenBank accession: L33765), and the similarity coefficient was 1.00. To best of our knowledge, this is the inaugural documentation of 16SrII Group-related phytoplasma infecting cowpea in Hainan, China, and lays the groundwork for further research on the dissemination of cowpea phytoplasma disease within China.

Teaching STEAM in the shaolin staff program: ways to stimulate student engagement in learning.

With the advancement of technology and change in education concepts, applying STEAM pedagogy to physical education has become an innovative trend. This study investigates whether physics analysis based on STEAM concepts can increase junior high students' participation in learning Shaolin Staff. Forty students were randomly assigned to experimental and control groups. The mean and standard deviation of age in the experimental group was 13.95 ± 0.83, and in the control group was 13.85 ± 0.81. The experimental group received STEAM teaching involving physics analysis, while the control group received conventional movement instruction. Student learning engagement was evaluated through questionnaires. Results are expected to show the experimental group being more engaged in learning. Introducing physics analysis may deepen understanding of related principles to movements. The study's results found that the scores of motivation, attention, and intention to learn independently were significantly higher in the experimental group than in the control group (p < 0.01). The scores of interfering emotions were significantly lower in the experimental group than in the control group (p < 0.01), which verified that the STEAM teaching method could effectively improve learning engagement. This study promotes STEAM education in martial arts and provides insights on utilizing STEAM to boost student engagement.

N6-methyladenosine (m6A) methyltransferase WTAP-mediated miR-92b-5p accelerates osteoarthritis progression.

The study was design to investigate the functional roles of Wilms tumor 1-associated protein (WTAP), an enzyme catalyzes m6A modification, in the pathogenesis of osteoarthritis (OA) and further elucidate its possible regulatory mechanism. Herein, we discovered that WTAP was outstandingly upregulated in chondrocyte stimulated with Lipopolysaccharide (LPS) and cartilage tissue of patients with OA. Functional studies have demonstrated that WTAP knockdown enhances proliferation ability, suppresses apoptosis, and reduces extracellular matrix (ECM) degradation in an LPS-induced OA chondrocyte injury model and ameliorates cartilage damage in a destabilizing the medial meniscus (DMM)-induced OA mice model. Conversely, overexpression of WTAP contributes to the opposite effects. Mechanistically, our data has demonstrated that m6A modification mediated by WTAP promotes the maturation of pri-miR-92b to miR-92b-5p, thereby enhancing the targeted inhibitory function of miR-92b-5p on TIMP4. Furthermore, we have discovered that WTAP can directly facilitate the degradation of TIMP4 mRNAs in a YTHDF2-dependent manner. In a nutshell, our findings suggested that WTAP knockdown alleviated OA progression by modulating the miR-92b-5p/TIMP4 axis in an m6A-dependent manner. Our study disclosed that WTAP-mediated m6A modification displayed a crucial role in OA development and suggested that targeting WTAP could be a promising preventive and therapeutic target for patients with OA. Video Abstract.

First Report of 16SrII Group Related Phytoplasma Associated with Areca Palm Yellow Leaf Disease on Areca catechu in China.

The areca palm, Areca catechu L., family Arecaceae is an important herbal medicine which has potential for the treatment of parasitic diseases, digestive function disorders and depression (Peng et al. 2015). Yellow leaf disease (YLD), caused by phytoplasma, is a destructive disease of Areca catechu. In 1981, the YLD was first discovered in Tunchang, Hainan, China. According to the investigation in 2020, the occurrence area of YLD was 32 102.38 hm2 in Hainan, China, resulting in 50%-60% yield loss. Previous researchers based on 16S rDNA gene PCR amplification analysis showed that YLD in Hainan was caused by 16SrI group phytoplasma (Che et al. 2010). In August, 2022, yellow leaf symptoms were observed on middle and lower leaves of Areca catechu. Forty symptomatic plants and three asymptomatic samples were collected in Wenchang, Hainan, China (19°33'9″N, 110°48'5″E). Forty-three samples (0.1g each) were used to extract total DNA (TIANGEN plant genomic DNA extraction kit). Phytoplasma universal primers named P1/P7 (Schneider et al. 1995) and R16F2n/R16R2 (Gundersen and Lee 1996) for 16Sr DNA and primers named fTuf1/rTuf1 and fTufu/rTufu (Schneider et al. 1997) for tuf genes were used for amplifying phytoplasma sequences from isolated DNA samples by nested PCR. No fragment was amplified in asymptomatic plants and four out of forty symptomatic samples could amplify target fragment. R16F2n/R16R2 amplicons (1 248 bp) and fTufu/rTufu amplicons (845 bp) from four symptomatic Areca catechu samples were sequenced in BGI (https://genomics.cn/). The 16Sr DNA GenBank accession numbers of four positive strains (named HNWC5, HNDZ1, HNDZ3 and HNDZ6) were OQ586072, OQ586085, OQ586086, OQ586087, respectively and the tuf GenBank accession numbers were OQ595209, OQ595210, OQ595211, OQ595212, respectively. Sequence alignment showed that the 16S rDNA and tuf sequence of HNDZ1, HNDZ3 and HNDZ6 were 100% consistent. 16S rDNA of HNWC5 was 99.96% consistent with HNDZ1 and tuf of HNWC5 was 98.31% consistent with HNDZ1. Interestingly, blast search based on 16S rDNA gene of HNWC5 showed 100% sequence identity with that of 16SrII group phytoplasma such as 'Eclipta prostrata' phytoplasma strain Ep1(MH144204.1), 'Aeschynomene americana' phytoplasma isolate AA1(MH231157.1) and 'Acacia confusa' witches'-broom phytoplasma isolate HK6(ON408364.1). Blast search based on tuf gene of HNWC5 showed 98.7% sequence identity with that of bamboo witches'-broom phytoplasma (FJ853160.1) and 91.02% sequence identity with that of 'podocarpus nagi' fasciation phytoplasma (KR633146) and 90.78% sequence identity with that of 'Musa acuminata' elephantiasis disease phytoplasma (MF983708). The phylogenetic tree was constructed based on 16Sr DNA gene by MEGA 7.0 employing neighbor-joining (NJ) method with 1000 bootstrap value (Kumar et al. 2016). The result indicated that the HNWC5, HNDZ1, HNDZ3 and HNDZ6 phytoplasma strains clustered a subclade in 16SrII group. The virtual RFLP analysis based on the 16Sr DNA gene sequence was performed by the online phytoplasma classification tool iPhyClassifier (Zhao et al. 2009) using restriction endonucleases of AluI, BamHI, BfaI, BstUI, DraI, EcoRI, HaeIII, HhaI, HinfI, HpaI, HpaII, KpnI, Sau3AI, MseI, RsaI, SspI and TaqI. The result indicated that HNWC5 was most similar to the reference pattern of peanut witches'-broom phytoplasma (16SrII-A subgroup, GenBank accession: L33765) and the pattern similarity coefficient of HNWC5 is 1.00. However, the HpaII restriction endonuclease pattern of HNDZ1, HNDZ3 and HNDZ6 was different from L33765 and the similarity coefficient was 0.97, which indicated this strain may represent a new subgroup within the 16SrII group. To our knowledge, this is the first report of 16SrII group related phytoplasma associated with YLD on Areca catechu in China. Our study contributes to understanding the polymorphism of phytoplasma causing YLD and provides an important reference for pathogen specific detection.

First Report of 16SrI-B Subgroup Related Phytoplasma Associated with Yellows Symptoms of Rubus cochinchinensis in China.

Rubus cochinchinensis, an important traditional Chinese medicine in China is used to treat rheumatic arthralgia, bruises and lumbocrural pain (He et al.2005). In January 2022, yellow leaves of R. cochinchinensis were found in Tunchang City, Hainan Province, a tropical island in China. Chlorosis spread along the direction of vascular tissue while the leaf veins remain green (Fig. 1). In addition, the leaves were slightly shrunken and the growth vigor is poor (Fig. 1). By survey, we found the incidence of this disease was about 30%. Three etiolated samples and three healthy samples (0.1g each) were used to extract total DNA (TIANGEN plant genomic DNA extraction kit). Using nested PCR method, phytoplasma universal primers P1 / P7 (Schneider et al., 1995) and R16F2n / R16R2 (Lee et al. 1993) were used to amplified phytoplasma 16S rDNA gene. Primers rp F1 / R1 (Lee et al. 1998) and rp F2 / R2 (Martini et al. 2007) were used to amplified rp gene. 16S rDNA gene and rp gene fragments were amplified from three leaf etiolated samples, but not from healthy samples. The amplified fragments were cloned and sequenced, and the sequences were assembled by DNASTAR11. By sequence alignment, we found the obtained 16S rDNA and rp gene sequences of three leaf etiolated samples were same. The length of 16S rDNA fragment was 1237 bp (accession number: ON944105) and the length of rp gene fragment was 1212 bp (accession number: ON960069). The phytoplasma strain was named as 'R. cochinchinensis' yellows leaf phytoplasma (RcT), RcT-HN1 strain. The 16S rDNA gene sequence of RcT-HN1is 99.8% consistent with 16SrI-B subgroup members such as the 'Brassica napus' dwarf phytoplasma strain WH3 (MG599470.1), Chinaberry yellows phytoplasma strain LJM-1(KX683297.1) and Arecanut yellow leaf disease phytoplasma strain B165 (FJ694685.1). The rp gene sequence of RcT-HN1 is 100% consistent with rpI-B subgroup members such as the 'Salix tetradenia' witches'-broom phytoplasma strain YM-1 (KC117314.1) and Chinaberry witches'-broom phytoplasma strain Hainan (EU348781.1). The phylogenetic tree analysis, based on concatenated 16S rDNA-rp gene sequence of same group phytoplasma by MEGA 7.0 employing neighbor-joining (NJ) method with 1000 bootstrap value, were performed (Kumar et al., 2016). The results showed that RcT-HN1 phytoplasma strain formed a subclade in aster yellows group B subgroup (Fig. 2). The virtual RFLP analysis based on the 16S rRNA gene fragment of RcT-HN1 phytoplasma strain was performed by the interactive online phytoplasma classification tool iPhyClassifier (Zhao et al., 2009). The results showed that the phytoplasma strain was same as the reference pattern of the onion yellows phytoplasma of 16SrI-B (GenBank accession: AP006628), and the similarity coefficient was 1.00. This is the first report that 16SrI-B subgroup related phytoplasma infected R. cochinchinensis and caused yellows symptoms in China. The discovery of the disease is helpful to the study of the spread of phytoplasma-related diseases and protect R. cochinchinensis resources.

Calcitriol-Loaded Multifunctional Nanospheres with Superlubricity for Advanced Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro. Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression.

OBJECTIVES: Increasing evidence have demonstrated the N6-methyladenosine (m6A) plays critical roles in osteoarthritis (OA) progression, but the role of m6A in OA has not been completely illuminated. Herein, we investigated the function and underlying mechanism of m6A demethylase fat mass and obesity-associated protein (FTO) in OA progression. MATERIALS AND METHODS: The FTO expression was detected in mice OA cartilage tissues and lipopolysaccharide (LPS)-stimulated chondrocytes. Gain-of-function assays was used to evaluate the role of FTO in OA cartilage injury in vitro and in vivo. The miRNA-sequencing, RNA-binding protein immunoprecipitation (RIP), luciferase reporter assay, and in vitro pri-miRNA processing assays were conducted to confirm that FTO modulated the pri-miR-3591 process in an m6A-dependent manner and then the binding sites of miR-3591-5p with PRKAA2. RESULTS: FTO was outstandingly downregulated in LPS-stimulated chondrocytes and OA cartilage tissues. FTO overexpression enhanced the proliferation, suppressed apoptosis, and decreased degradation of extracellular matrix in LPS-induced chondrocytes, whereas FTO knockdown contributed to the opposite effects. In vivo animal experiments showed that FTO overexpression markedly alleviated OA mice cartilage injury. Mechanically, FTO-mediated m6A demethylation of pri-miR-3591 leaded to a maturation block of miR-3591-5p, which relieved the inhibitory effect of miR-3591-5p on PRKAA2 and then promoted the increase of PRKAA2, thereby alleviating OA cartilage damage. CONCLUSIONS: Our results attested that FTO alleviated the OA cartilage damage by mediating FTO/miR-3591-5p/PRKAA2 axis, which provided fresh insights into the therapeutic strategies for OA.

Cutoff points of T1 rho/T2 mapping relaxation times distinguishing early-stage and advanced osteoarthritis.

Introduction: The histopathology grading system is the gold standard post-operative method to evaluate cartilage degeneration in knee osteoarthritis (OA). Magnetic resonance imaging (MRI) T1 rho/T2 mapping imaging can be used for preoperative detection. An association between histopathology and T1 rho/T2 mapping relaxation times was suggested in previous research. However, the cutoff point was not determined among different histopathology grades. Our study aimed to determine the cutoff point of T1 rho/T2 mapping. Material and methods: T1 rho/T2 mapping images were acquired from 80 samples before total knee replacements. Then the histopathology grading system was applied. Results: The mean T1 rho/T2 mapping relaxation times of 80 samples were 39.17 ms and 37.98 ms respectively. Significant differences were found in T1 rho/T2 mapping values between early-stage and advanced OA (p < 0.001). The cutoff point for T1 rho was 33 ms with a sensitivity of 94.12 (95% CI: 80-99.3) and a specificity of 91.30 (95% CI: 79.2-97.6). The cutoff point for T2 mapping was suggested as 35.04 ms with a sensitivity of 88.24 (95% CI: 72.5-96.7) and specificity of 97.83 (95% CI: 88.5-99.9). After bootstrap simulation, the 95% CI of the T1 rho/T2 mapping cutoff point was estimated as 29.36 to 36.32 ms and 34.8 to 35.04 ms respectively. The area under the PR curve of T1 rho/T2 mapping was 0.972 (95% CI: 0.925-0.992) and 0.949 (95% CI: 0.877-0.989) respectively. Conclusions: The cutoff point of T1 rho relaxation times, which was suggested as 33 ms, could be used to distinguish early-stage and advanced OA.

Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.

Long-term use of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) shows clinical benefits for rheumatoid arthritis (RA) treatment. However, there are growing concerns over the adverse effects of systemic drug administration. Therefore, a strategy that can enhance drug bioavailability while minimizing side effects is urgently needed, but remains a challenge in RA therapy. To this end, here we conjugated MTX with a supramolecular self-assembling hydrogel composed of d-amino acids with a sequence of GDFDFDY. It was shown that MTX-GDFDFDY hydrogels exhibited a favorable drug selectivity behavior that they increased MTX toxicity toward RA synoviocytes, but reduce toxicity toward normal cells. Moreover, MTX-GDFDFDY hydrogels not only effectively inhibited the proliferation and migration of RA synoviocytes, but also inhibited the polarization of proinflammatory M1 type macrophages to reduce inflammation. After intra-articularly injected the hydrogels into the joints of adjuvant induced arthritis (AIA) mice, we found that MTX-GDFDFDY hydrogels significantly alleviated RA syndromes of joint swelling and fever compared to L-configuration MTX-GFFY hydrogels and free MTX. Furthermore, MTX-GDFDFDY hydrogels successfully protected cartilage though inhibiting synovial invasion and inflammation without causing systematic side effects. Therefore, d-amino acids supramolecular hydrogels can serve as an efficient and safe drug delivery system, showing a promising potential to improve RA therapy.

Prediction of 90-Day Local Complications in Patients After Total Knee Arthroplasty: A Nomogram With External Validation.

BACKGROUND: Local complications after total knee arthroplasty (TKA) significantly affect the patient's prognosis. Nomograms can be a useful tool for predicting such complications. PURPOSE: To compare the preoperative and intraoperative factors of patients who underwent TKA with and without complications and to construct and validate a nomogram based on selective predictors of local complications within 90 days postoperatively. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The nomogram was developed in a primary cohort that consisted of 410 patients who underwent primary TKA at the authors' institution between January 2015 and September 2018. Predictor variables included 4 major local complications that can occur within 90 days: reoperation (including implant revision or removal for any reason and manipulation under anesthesia), infection, bleeding requiring ≥4 unit transfusion of red blood cells within 72 hours of surgery, and peripheral nerve injury. The authors used least absolute shrinkage and selection operator (LASSO) regression analysis for data dimension reduction and feature selection. Multivariable logistic regression analysis was used to develop the nomogram. Performance of the nomogram was assessed using C-index, calibration plot, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA). The model was subjected to bootstrap validation and external validation using a prospective cohort of 249 patients. RESULTS: Four significantly prognostic factors were incorporated into the nomogram: age-adjusted Charlson Comorbidity Index, American Society of Anesthesiologists score, tourniquet time, and estimated intraoperative blood loss. The model displayed good discrimination, with a C-index of 0.819 and an AUC of 0.819. The calibration curves showed optimal agreement between nomogram prediction and actual observation. A high C-index value of 0.801 could still be reached in bootstrap validation. Application of the nomogram in the validation cohort showed good discrimination (C-index, 0.731) and good calibration. DCA demonstrated that the nomogram was clinically useful. CONCLUSION: The authors developed and validated a novel nomogram that can provide individual prediction of local complications within 90 days for patients after TKA. This practical tool may be conveniently used to estimate individual risk and help clinicians take measures to minimize or prevent the incidence of complications.

A ZIF-8-based multifunctional intelligent drug release system for chronic osteomyelitis.

Chronic osteomyelitis (COM) is an inflammatory bone disease caused by bacterial infection. Conventional treatment with antibiotics is prone to resistance and other side effects, and it is ineffective against inflammation caused by infection and bone loss. To treat COM comprehensively, based on the acidic microenvironment of osteomyelitis, we used ZIF-8 and celecoxib to construct a multifunctional intelligent drug release system with pH response effect, named CEL@ZIF-8. Material characterization revealed that celecoxib is successfully loaded into ZIF-8. Ion release and drug release experiments indicated that CEL@ZIF-8 can respond well to the pH and intelligently control the release of ions and drugs. Antibacterial assays manifested that CEL@ZIF-8 is able to inhibit the growth of bacteria significantly. In vitro cell experiments demonstrated that CEL@ZIF-8 can significantly up-regulate the expression of osteogenesis-related cytokines and down-regulate the levels of inflammatory factors. Studies verify that the novel drug release system possesses multiple functions: antibacterial, osteogenesis, anti-inflammatory and intelligent release, suggesting a tremendous clinical promise for the treatment of COM.

An Mg-MOFs based multifunctional medicine for the treatment of osteoporotic pain.

Bone pain is the primary problem for patients with osteoporosis. Ketoprofen is clinically used to treat osteoporotic pain, while long-term oral administration of ketoprofen can cause some side effects. In addition, osteoporosis is also accompanied by bone mass loss and inflammation. In this study, we designed a multifunctional drug (Ket@Mg-MOF-74) adopted Mg-MOF-74 to load ketoprofen to treat osteoporotic pain, bone loss and inflammation comprehensively. Mg-MOF-74 was prepared, and the physicochemical characterization proved that it had excellent physical and chemical stability. Ket@Mg-MOF-74 was synthesized by post-synthetic modification method and a high loading rate of ketoprofen was confirmed. Drug release and ion release experiments indicated Ket@Mg-MOF-74 had a good controlled release of ketoprofen and Mg in solution. Cell experiments in vitro proved the compound drug could significantly reduce the expression of pain-related genes of cyclooxygenase 2 (COX2), obviously up-regulated the expression of osteogenic cytokines and remarkably down-regulated the secretion of pro-inflammatory factors. Therefore, Ket@Mg-MOF-74 is believed a promising painkiller for osteoporotic bone pain, with the function of anti-inflammatory and promoting bone formation.

Histological Grade and Magnetic Resonance Imaging Quantitative T1rho/T2 Mapping in Osteoarthritis of the Knee: A Study in 20 Patients.

BACKGROUND Magnetic resonance imaging (MRI) of osteoarthritis (OA) of the knee is a preoperative method of joint assessment. Histology of the joint is invasive and performed after surgery. T1rho/T2 MRI mapping is a new preoperative method of quantifying joint changes. This study aimed to analyze and compare the histological changes in the joint cartilage with the use of quantitative T1rho/T2 MRI mapping in patients with OA of the knee. MATERIAL AND METHODS Twenty patients with OA of the knee (20 knees) underwent preoperative MRI with T1rho mapping, T2 mapping, T1-weighted, and T2-weighted fat-suppressed MRI sequences. The degree of OA of the knee on MRI was graded according to the Osteoarthritis Research Society International (OARSI) criteria and the Kellgren-Lawrence grading system. Histological grading of OA used the OARSI criteria. Four tibiofemoral condyles were assessed histologically, and the degree of cartilage destruction was determined using the OARSI criteria. Two investigators performed cartilage segmentation for T1rho/T2 values. RESULTS Histology of the four knee joint condyles confirmed mild to severe OA. The histology of the cartilage thickness (P<0.001) and the MRI findings of the distal medial condyle (P<0.00) were significantly different from the other three knee joint condyles. The T2 and T1rho values of each condyle were significantly correlated with the histological grade (II-IV) of the joint condyles, including the cartilage volume, cartilage defects, thickness, and bone lesions (P<0.05). CONCLUSIONS In 20 patients with OA of the knee, preoperative T2/T1rho MRI identified Grade II-IV OA changes in the joint.

Visible-Light-Enabled Oxidative Coupling of Alkenes with Dialkylformamides To Access Unsaturated Amides.

A practical and direct method for oxidative cross-coupling of alkenes with dialkylformamides is established employing visible-light-enabled photoredox catalysis. This strategy allows efficient access to diverse unsaturated amides under mild reaction conditions. The application of an appropriate diaryliodonium salt was demonstrated to be critical to the success of this process. This catalyst system is well tolerant of a variety of useful functional groups.

Efficacy and Safety of Tranexamic Acid for Controlling Bleeding During Surgical Treatment of Intertrochanteric Fragility Fracture with Proximal Femoral Nail Anti-rotation: A Randomized Controlled Trial.

BACKGROUND: Intertrochanteric fragility fracture (IFF) treated with proximal femoral nail anti-rotation (PFNA) is associated with significant hidden blood loss and high blood transfusion rate. The purpose of the present study was to evaluate the efficacy and safety of tranexamic acid (TXA) in reducing blood loss in these patients. MATERIALS AND METHODS: Consecutive eligible patients were recruited and randomly assigned to a TXA group or a control group. The TXA group received 15 mg/kg body weight of TXA intravenously 15 min before incision and the same dose 3 h later. The control group received 100 mL of saline intravenously 15 min before incision. The efficacy outcomes included the total perioperative blood loss, postoperative transfusion rate, postoperative hemoglobin level, and length of the hospital stay. The safety outcomes were the incidence of thrombotic events and the mortality rate within 6 weeks after surgery. RESULTS: We had 44 patients in the TXA group and 46 patients in the control group for the final analysis. The TXA group had significantly lower total perioperative blood loss than the control group (384.5 ± 366.3 mL vs. 566.2 ± 361.5 mL; P < 0.020). Postoperative transfusion rate was 15.9% in the TXA group versus 36.9% in the control group (P = 0.024). Each group had one patient with postoperative deep venous thrombosis. In the control group, three patients had cerebral infarction, and one patient died within 6 weeks after the operation. CONCLUSION: Intravenous TXA is effective in reducing total perioperative blood loss and transfusion rate in IFF treated with PFNA. No increased risk of thrombotic events was observed with the use of TXA; however, this study was underpowered for detecting this outcome. Further research is necessary before TXA can be recommended for high-risk patients.

Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which synovial fibroblast-like cells (FLSs) play an important role in RA development and is known to be lack of effective therapy. Thus, novel therapeutic strategies are greatly needed for treatment of RA. Metformin, a first-line drug for the treatment of type 2 diabetes, has been reported to inhibit the proliferation of a variety of tumor cells. In this study, we demonstrated that metformin could inhibit the RA-FLS proliferation in dose- and time-dependent manner. Our cell viability MTT test and 5-ethynyl-2-deoxyuridine incorporation assay showed that metformin inhibited the RA-FLSs proliferation with a time- and concentration-dependent increase. More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs. In summary, these results demonstrate that metformin can effectively inhibit RA-FLS proliferation through inducing cell cycle and upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation. Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin. Our results indicate that metformin may provide a new way of thinking for the treatment of RA.

Visible-light-promoted oxidation/condensation of benzyl alcohols with dialkylacetamides to cinnamides.

Oxidative cross-coupling reactions of benzyl alcohols with N,N-dialkylacetamides were developed only employing oxygen as the terminal oxidant, efficiently providing a new, novel protocol for the construction of multifunctionalized cinnamides with the synergistic effects of KOH, organic photocatalyst eosin Y, and visible light irradiation at room temperature. A broad substrate scope and mild reaction conditions are the prominent features of this transformation.

Visible-Light-Enabled Oxidative Alkylation of Unactivated Alkenes with Dimethyl Sulfoxide through Concomitant 1,2-Aryl Migration.

Metal-free oxidative radical 1,2-alkylarylation of unactivated alkenes with the α-C(sp3)-H bond of dimethyl sulfoxide has been developed. This study realizes a new, conceptually novel technology for convenient construction of a variety of α-aryl-γ-methylsulfinyl ketones in good-to-excellent yields with the synergistic interactions of visible light irradiation, organic fluorophores 4CzIPN, and hypervalent iodine(III) reagent under transition-metal free conditions. A remarkable kinetic isotope effect was observed, which helped provide insight into the reaction's mechanistic course.

Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus-mediated cotransfection of the two genes into rat bone marrow-derived MSCs. The successful co-expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2-induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.