Association between hip and knee osteoarthritis with falls: A systematic review and meta-analysis.

OBJECTIVE: To examine the association between hip and knee osteoarthritis (OA) and falls. Potentially relevant articles that examine the association between hip, knee, radiological, and self-reported OA and falls were retrieved from PubMed, EMBASE, Scopus, and Web of Science up until March of 2020. METHODS: The pooled risk ratios (RRs) as well as their related 95% confidence intervals (CIs) were calculated. Statistic and subgroup analyses were performed. A total of 21 studies involving 146 965 participants were included. RESULTS: No association was found between hip OA and falls. The pooled RRs value suggested a higher prevalence of falls in knee OA patients (RR = 1.35, 95% CI: 1.20 to 1.51, P < .00001) and self-reported OA (RR = 1.33, 95% CI: 1.23 to 1.45, P < .00001) than in non-OA subjects. The pooled RR value suggested no difference between prevalence of falls in radiological OA patients compared to non-OA subjects (RR = 1.82, 95% CI: 0.89 to 3.73, P = .10). Both radiological and self-reported knee OA seem to be positively associated with falls, while no obvious association was found between hip OA and falls. CONCLUSIONS: Therefore, knee OA is a risk factor for falls which should be closely monitored.

Impact factors and obstetric outcomes of preeclampsia in twin pregnancies by prepregnancy body mass index: a six-year retrospective cohort study.

OBJECTIVES: Among many risk factors for preeclampsia (PE), prepregnancy body mass index (BMI) is one of few controllable factors. However, there is a lack of stratified analysis based on the prepregnancy BMI. This study aimed to determine the influencing factors for PE and assess the impact of PE on obstetric outcomes in twin pregnancies by prepregnancy BMI. METHODS: This was a retrospective cohort study between January 1, 2017, and December 31, 2022, in Southwest China. Impact factors and associations between PE and obstetric outcomes were analyzed separately for twin pregnancies with prepregnancy BMI < 24kg/m2 (non-overweight group) and BMI ≥ 24kg/m2 (overweight group). RESULTS: In total, 3602 twin pregnancies were included, of which, 672 women were allocated into the overweight group and 11.8% of them reported with PE; 2930 women were allocated into the non-overweight group, with a PE incidence of 5.6%. PE had a negative effect on birthweight and increased the incidence of neonatal intensive care unit admission in both the overweight and non-overweight groups (43.0% vs. 28.0%, p = .008; 45.7% vs. 29.1%, p < .001). Among overweight women, PE increased the proportion of postpartum hemorrhage (15.2% vs. 4.4%, p < .001). After adjustments, multivariate regression analysis showed that excessive gestational weight gain (aOR = 1.103, 95% CI: 1.056-1.152; aOR = 1.094, 95% CI: 1.064-1.126) and hypoproteinemia (aOR = 2.828, 95% CI: 1.501-5.330; aOR = 6.932, 95% CI: 4.819-9.971) were the shared risk factors for PE in both overweight and non-overweight groups. In overweight group, in vitro fertilization was the other risk factor (aOR = 2.713, 95% CI: 1.183-6.878), whereas dichorionic fertilization (aOR = 0.435, 95% CI: 0.193-0.976) and aspirin use during pregnancy (aOR = 0.456, 95% CI: 0.246-0.844) were protective factors. Additionally, anemia during pregnancy (aOR = 1.542, 95% CI: 1.090-2.180) and growth discordance in twins (aOR = 2.451, 95% CI: 1.215-4.205) were connected with an increased risk of PE only in non-overweight twin pregnancies. CONCLUSIONS: Both discrepancy and similarity of impact factors on developing PE were found between overweight and non-overweight twin pregnancies in this study. However, the dosage and initiation time of aspirin, as well as twin chorionicity on the occurrence of PE in two subgroups, are still debated.

Applications and prospects of cryo-EM in drug discovery.

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Microanatomical study on the functional origin and direction of the thoracodorsal nerve from the trunks of brachial plexus.

Ipsilateral C7 nerve root transfer or neurotization has been used for the repair of brachial plexus avulsions. In this procedure, the ipsilateral C7 nerve root is used as a donor nerve and is implanted into the damaged nerve of the brachial plexus in order to reinnervate distal muscles. However, this procedure may result in unintended injury to the thoracodorsal nerve, which receives motor fascicles form the cervical nerves of C6, C7, and C8, but mainly from C7. Damage to the thoracodorsal nerve ultimately results in weakness or paralysis of the latissimus dorsi muscle, which it innervates. In the present study, 20 adult cadaveric brachial plexus specimens and 3 fresh specimens were dissected using microscopy. The origin and direction of motor fascicles from the three trunks of the brachial plexus to the thoracodorsal nerve were investigated. Motor fiber counts of C7 and the thoracodorsal nerve were also performed. Several observations can be made: (1) The origin of the thoracodorsal nerve can be divided into three types: Type A, the thoracodorsal nerve originated from the superior and middle trunks; Type B, the thoracodorsal nerve originated from the inferior and middle trunks; and Type C, the thoracodorsal nerve originated from all three trunks. (2) More than 52% of the motor fibers in the thoracodorsal nerve originated in the C7 nerve root. (3) Motor fascicles from C7 to the thoracodorsal nerve were mostly localized in the posterior-internal part of C7 at the trunk-division boundary. In conclusion, we suggest that: (1) Because of variation in the origin of the thoracodorsal nerve, electromyography should be routinely performed intraoperatively during C7 nerve root transfer to determine the origin type and avoid thoracodorsal fascicle injury. (2) Preservation of the posterior-internal part of C7 (selective C7 transfer) can protect thoracodorsal nerve fascicles from damage and prevent postoperative dysfunction of the latissimus dorsi muscle.

Steroid-associated hip joint collapse in bipedal emus.

In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients.

Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures.

BACKGROUND: Treatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated. Using an alternative methods, in vitro organotypic slice culture method, would be useful to transplant cells and assessing the effects. This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures. METHODS: Bone marrow aspirates were obtained from posterior superior iliac spine (PSIS) of patients that had undergone spinal fusion due to a degenerative spinal disorder. For cell imaging, mesenchymal precursor cells (MPCs) were pre-stained with PKH-26 just before transplantation to canine spinal cord slices. Canine spinal cord tissues were obtained from three adult beagle dogs. Spinal cords were cut into transverse slices of 1 mm using tissue chopper. Two slices were transferred into 6-well plate containing 3 ml DMEM with antibiotics. Prepared MPCs (1×10(4)) were transplanted into spinal cord slices. On days 0, 3, 7, 14, MPCs were observed for morphological changes and expression of neuronal markers through immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The morphological study showed: spherical cells in the control and experiment groups on day 0; and on day 3, cells in the control group had one or two thick, short processes and ones in the experiment group had three or four thin, long processes. On day 7, these variously-sized processes contacted each other in the experiment group, but showed typical spindle-shaped cells in the control group. Immunofluorescence showed that PKH-26(+) MPCs stained positive for NeuN(+) and GFAP(+) in experimental group only. Also RT-PCR showed weak expression of ß-tubulin III and GFAP. CONCLUSIONS: Human bone marrow mesenchymal precursor cells (hMPCs) have the potential to differentiate into the neuronal like cells in this canine spinal cord organotypic slice culture model. Furthermore, these findings suggested the possibility that these cells can be utilized to treat patients with spinal cord injuries.

Resveratrol inhibits interleukin 1ß-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity.

In chondrocytes, resveratrol, a natural SIRT1 activator, exerts an anti-inflammatory response via inhibition of nuclear factor kappaB (NF-κB). Given that SIRT1 inhibits the transactivation potential of NF-κB by deacetylating acetylated lysines in p65, the NF-κB subunit, we investigated the effects of resveratrol-activated SIRT1 on articular chondrocytes. We found that when chondrocytes were stimulated with interleukin 1ß (IL-1ß), the time- and dose-dependent expression of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was suppressed by resveratrol. Resveratrol-activated SIRT1 mediated this suppression. SIRT1 suppressed not only the nuclear translocation of NF-κB but also the acetylation of p65. Furthermore, acetylated Lys310 in p65, which must be present for transactivation activity, was the immediate downstream target of SIRT1. Therefore, SIRT1 protects against the inflammatory response induced by IL-1ß in articular chondrocytes. Resveratrol, as an activator of SIRT1, merits consideration as a therapeutic agent in the treatment and prevention of osteoarthritis.