Learning curve analysis of robotic-assisted total knee arthroplasty with a Chinese surgical system.

PURPOSE: The aim of this study was to analyze the learning curve of total operative time, bone cutting accuracy, and limb alignment in total knee arthroplasty (TKA) using a Chinese image-based knee surgery robot known as HURWA. Additionally, a comparison was conducted with conventional TKA to ascertain the benefits of robotic-assisted TKA. METHODS: In this retrospective study, we analyzed a series of patients (n = 90) who underwent robotic-assisted total knee arthroplasty using the HURWA robot between December 2021 and October 2022. The procedures were performed by one of three orthopedic surgeons with varying levels of experience. As a control group, we selected the last 30 conventional TKA cases performed by each of these three surgeons. To determine the learning curve, we recorded the operative time, bone cutting error, and pre- and post-surgery radiographs. RESULTS: The study found no significant differences in total operative time, bone cutting accuracy, or limb alignment among the three surgeons. Of the three surgeons, surgeon 1, who had the most experience in joint arthroplasty, reached the learning curve in case 8, with the shortest bone cutting time and robot time. Surgeon 2 reached the learning curve in case 16, while surgeon 3 reached the learning curve in case 9. There was no observable learning curve effect for bone cutting accuracy and limb alignment. However, the percentage of cases where limb alignment differed from preoperative planning by 3° or less was higher in robotic-assisted TKA (77.97%) than in conventional TKA (47.19%). CONCLUSION: The study determined that the learning curve for robotic-assisted TKA using the HURWA knee surgery robot ranged from 8 to 20 cases. No observable learning curve effect was detected for bone cutting accuracy or limb alignment. Experienced surgeons using the HURWA robot for bone cutting took less time and reached the learning curve earlier. The HURWA robot achieved better limb alignment without depending on the experience of conventional TKA.

Clinical course of patients with severe SARS-CoV-2 infection co-treatment with Jin Si Herbal Tea in Eastern Taiwan: A retrospective cohort study.

Introduction: Coronavirus disease-2019 (COVID-19) has affected more than 608 million people and has killed 6.5 million people in the world. A few studies showed traditional Chinese medicine can be beneficial for COVID-19 treatment. An herbal preparation Jin Si Herbal Tea (JS) was formulated with herbal extracts known for their potential to decrease spike protein and ACE2 interaction, 3CL, and TRPMSS2 protease activity, and thus aimed to evaluate the clinical course of JS co-treatment along with the usual treatment schedule given for severe COVID-19 patients. Methods: This retrospective cohort study included patients with severe COVID-19 admitted to Hualien Tzu Chi Hospital between June and July 2021. All the patients were co-treated with JS and the primary outcome was death. The secondary outcomes included laboratory exam, Ct value, clinical course, and hospital stays. There were 10 patients recruited in this study and divided into < 70 years and ≧ 70 years groups (n = 5 in each group). Results: Older patients (≧70 years) had a higher Charlson Comorbidity Index, VACO index, and lower hemoglobin levels than < 70 years patients. The trend of lymphocyte count, LDH, D-dimer, and Ct value of non-survivors was not consistent with previous studies. The death rate was 20% and the recovery rate to mild illness in 14 days was 40%. Conclusion: In conclusion, this is the first clinical study of JS co-treatment in severe COVID-19 patients. JS co-treatment might reduce death rate and recovery time. Further large-scale clinical trials would be expected.

Modulation of dear enemy effects by male dusky warblers (Phylloscopus fuscatus) at different reproductive stages.

Territorial animals show less aggression during intrusion by neighbours than by strangers, a phenomenon known as the "dear enemy effect". Recent studies have shown that the dear enemy effect is variable in some birds throughout the breeding season. However, there is limited research on changes in dear enemy effects in songbirds during the breeding season. In this study, we monitored dusky warblers (Phylloscopus fuscatus) throughout their breeding stages, conducting playback experiments simulating incursions by neighbours and strangers during their egg-laying and incubation/nestling periods, and recording physical responses and song responses from territory owners. The results showed that male dusky warblers responded similarly to neighbours and strangers during the female egg-laying period, but there was a significantly stronger response to strangers than to neighbours during the incubation/nestling period. This suggests that male dusky warblers adjust the intensity of their defences against neighbours according to the reproductive status of their own mate. This may be because neighbouring males threaten the paternity of territorial males during the egg-laying period, so territorial males demote the 'dear enemy' friendly relationships with their neighbours to defend their mate and paternity. In contrast, during the non-reproductive period of females, when neighbours are less of a threat to the paternity of territorial males, lowering defences against neighbouring males allow them to devote more time and energy to activities that improve their fitness, such as foraging and seeking extra-pair mating.

Activation and blockade of 5-HT4 receptors in the dorsal hippocampus enhance working and hippocampus-dependent memories in the unilateral 6-hydroxydopamine lesioned rats.

Cognitive dysfunction is a common symptom in Parkinson's disease (PD). Serotonin4 (5-HT4) receptors are richly expressed in the dorsal hippocampus (dHIPP) and play an important role in cognitive activities. However, the mechanism underlying the role of dHIPP 5-HT4 receptors in PD-related cognitive dysfunction remains unclear. Here we found that unilateral 6-hydroxydopamine lesions of the medial forebrain bundle increased the protein expression of 5-HT4 receptors in the dHIPP, decreased hippocampal theta rhythm, and impaired working memory and hippocampus-dependent memory in the T-maze and hole-board test, respectively. Both activation and blockade of dHIPP 5-HT4 receptors (agonist BIMU8 and antagonist GR113808) improved working memory and hippocampus-dependent memory in the lesioned rats, but not in sham rats. Activation of dHIPP 5-HT4 receptors increased hippocampal theta rhythm in the lesioned rats. The neurochemical studies showed that injection of BIMU8, GR113808 or GR113808/BIMU8 in the dHIPP increased the levels of dopamine in the medial prefrontal cortex (mPFC), dHIPP and amygdala, and the level of 5-HT in the amygdala in the lesioned rats, but not in sham rats. Injection of GR113808 or GR113808/BIMU8 into the dHIPP also increased the levels of noradrenaline in the mPFC, dHIPP and amygdala only in the lesioned rats. These results suggest that activation or blockade of dHIPP 5-HT4 receptors may improve the cognitive impairments in parkinsonian rats, which may be due to the increase of hippocampal theta rhythm, up-regulated expressions of 5-HT4 receptors in the dHIPP and the changes in the levels of monoamines in the relative brain areas.

Clinical Characteristics of Hospitalized Pediatric Patients With Hypertensive Crisis-A Retrospective, Single-Center Study in China.

Background: A hypertensive crisis is a medical emergency that causes acute damage to multiple organs. However, the etiology, clinical features, and prognosis of hypertensive crisis in Chinese children remain relatively unknown. The purpose of this study was to analyze the clinical characteristics of pediatric hypertensive crisis patients from a single center in China. Methods: We analyzed data from 70 children with hypertensive crisis between January, 2000, and January, 2022. The patients were divided into two groups: those diagnosed with a hypertensive emergency (n = 46) and those diagnosed with hypertensive urgency (n = 24). Baseline etiologies and risk factors were compared between the two groups. The following data were collected and analyzed: age, sex, weight, height, family history of hypertension, blood pressure, clinical manifestations of hypertensive crisis, underlying causes, biochemical indicators, and antihypertensive drugs. Results: The major symptoms of hypertensive crisis were headache (n = 31, 44.29%), followed by visual symptoms (n = 15, 21.43%), and dizziness (n = 13, 18.57%). Further analysis showed that the incidence of convulsions was significantly higher in patients with hypertensive emergency than those with hypertensive urgency (χ2 = 5.38, p = 0.02). The leading underlying causes were renal disease (n = 34, 48.57%), followed by vascular disease (n = 11, 15.71%), essential hypertension (n = 9, 12.86%), oncological disease (n = 9, 12.86%), central nervous system disease (n = 3, 4.29%), endocrine and metabolic diseases (n = 2, 2.86%), and other (one case with lead poisoning, one case with histiocytosis). End-organ damage occurred in 46 patients with hypertensive crisis, including retinal damage (n = 20, 43.48%), brain damage (n = 19, 41.30%), heart damage (n = 15, 32.61%), and renal damage (n = 3, 6.52%). Hypertensive crisis was most common among children aged 7-12 years. Among children aged 13-18 years, hypertensive urgency was more common than hypertensive emergency. The incidence of dyslipidemia, elevated serum creatinine, and elevated uric acid did not differ significantly between the two groups. Most patients with hypertensive crisis need combined antihypertensive therapy (n = 60, 85.71%). There were no cases of mortality. Conclusions: Hypertensive crisis is caused by secondary diseases, especially renal disease and vascular disease, in the majority of pediatric patients. Combination therapy with antihypertensive agents and treatment of secondary etiology results in a good prognosis.

Spinal 5-HT2A receptor is involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.

Application of dynamic display technology to identify gaps after pulmonary vein isolation in catheter ablation of atrial fibrillation.

BACKGROUND: The identification of post pulmonary vein isolation (PVI) gaps by activation and voltage maps is time-consuming. This study aimed to investigate the characteristics, efficiency and accuracy of LiveView dynamic display module (EnSite™ Dynamic Display; Abbott, Abbott Park, IL, USA) in unmasking post PVI gaps and conduction block line. METHOD: Twenty four patients with paroxysmal atrial fibrillation (PAF) who failed to achieve first-pass PVI or with recurrent PAF were enrolled. Ninety-six pulmonary veins (PVs) were evaluated, and gaps were identified in 25 (26.0%) PVs. The gap location was confirmed by activation and propagation maps; 110 frames on gaps and 118 frames on block lines were analyzed by using LiveView module. We defined isochronal crowding in the local activation time (LAT) mode as three colors between two adjacent electrodes. Each frame was classified as with or without isochronal crowding in LAT mode and one/continuous color or isochronal discontinuity in reentrant mode. The gray color inside the PVs was considered to represent conduction block. RESULT: The isochronal crowding could be found on both gap and block line in LAT mode, whereas isochronal discontinuity only presented on the block line in reentrant mode. The sensitivity and specificity of isochronal discontinuity or gray color in reentrant mode to identify block line were 61.0% and 100%, respectively. The sensitivity and specificity of isochronal crowding or gray color in LAT mode to identify block line were 71.2% and 71.8%, respectively. CONCLUSION: Reentrant mode in LiveView module is very specific in identifying block lines. We proposed an efficient, practical algorithm to differentiate the block line from PV gaps.

Effect of Low-Intensity Pulsed Ultrasound on the Graft-Bone Healing of Artificial Ligaments: An In Vitro and In Vivo Study.

BACKGROUND: As many researchers have focused on promoting the graft-bone healing of artificial ligaments, even with numerous chemical coatings, identifying a biosafe, effective, and immediately usable method is still important clinically. PURPOSE: (1) To determine whether a low-intensity pulsed ultrasound system (LIPUS) promotes in vitro cell viability and osteogenic differentiation and (2) to assess the applicability and effectiveness of LIPUS in promoting the graft-bone healing of artificial ligaments in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: Polyethylene terephthalate (PET) sheets and grafts were randomly assigned to control and LIPUS groups. MC3T3-E1 preosteoblasts were cultured on PET sheets. Cell viability and morphology were evaluated using a live/dead viability assay and scanning electron microscopy. Alkaline phosphatase activity, calcium nodule formation, and Western blot were evaluated for osteogenic differentiation. For in vivo experiments, the effect of LIPUS was evaluated via an extra-articular graft-bone healing model in 48 rabbits: the osteointegration and new bone formation were tested by micro-computed tomography and histological staining, and the graft-bone bonding was tested by biomechanical testing. RESULTS: Cell viability was significantly higher in the LIPUS group as compared with control (living and dead compared between control and LIPUS groups, P = .0489 vs P = .0489). Better adherence of cells and greater development of extracellular matrix were observed in the LIPUS group. Furthermore, LIPUS promoted alkaline phosphatase activity, calcium nodule formation, and the protein expression of collagen 1 (P = .0002) and osteocalcin (P = .0006) in vitro. Micro-computed tomography revealed higher surrounding bone mass at 4 weeks and newly formed bone mass at 8 weeks in the LIPUS group (P = .0014 and P = .0018). Histological analysis showed a narrower interface and direct graft-bone contact in the LIPUS group; the surrounding bone area at 4 weeks and the mass of newly formed bone at 4 and 8 weeks in the LIPUS group were also significantly higher as compared with control (surrounding bone, P < .0001; newly formed bone, P = .0016 at 4 weeks and P = .005 at 8 weeks). The ultimate failure load in the LIPUS group was significantly higher than in the control group (P < .0001 at 4 weeks; P = .0008 at 8 weeks). CONCLUSION: LIPUS promoted the viability and osteogenic differentiation of MC3T3-E1 preosteoblasts in vitro and enhanced the graft-bone healing of PET artificial ligament in vivo. CLINICAL RELEVANCE: LIPUS is an effective physical stimulation to enhance graft-bone healing after artificial ligament implantation.

Accuracy of the Horizontal Calibrator in Correcting Leg Length and Restoring Femoral Offset in Total Hip Arthroplasty.

Background: Limb length discrepancy (LLD) is one of the most common postoperative complications and can cause serious consequences. Poor recovery of femoral offset (OD) will result in weakness of the patient's external rotator muscles and affect the patient's postoperative function. The study is aimed to present a simple approach that compensates for the shortcomings of previous measuring devices and combines the advantages of different measuring devices to provide more accurate limb length and femoral offset restoration in total hip arthroplasty (THA). Methods: This study was a prospective controlled trial involving 89 patients with THA. Group I (n = 44) was used for intraoperative measurement of THA with our self-designed horizontal calibrator. Group II (n = 45) was measured by a traditional freehand technique. The main outcome indicators were measured on the Neusoft PACS, including LLD, femoral offset deviation, and operative time. IBM SPSS 23.0 was used for data analysis. Results: The independent sample t-test was performed for all the data. The operative time, preoperative radiographic LLD, and OD of Group I and Group II had no statistical significance. Postoperative LLD of Group I and Group II were 2.5 ± 2.1 mm (range -5.7 to 8.3 mm) and 6.2 ± 4.3 mm (range -18.0 to 15.2 mm), and the independent sample t-test data of both (P < 0.001; 95%CI = -5.1, -2.2) showed statistical significance. In Group I, there were 38 THAs with LLD <5 mm, accounting for 86% and there were 44 THAs with LLD <10 mm, accounting for 100%. In Group II, there were 20 THAs with LLD <5 mm, accounting for 44%. There were 36 THAs with LLD <10 mm, covering for 80%. There was no significant difference in postoperative femoral offset and OD. Conclusion: The horizontal calibrator can provide more accurate limb length and femoral offset recovery in THA. It is a simple surgical technique that does not add additionally surgical costs and does not significantly increase operative time, providing a new solution for surgeons to resolve postoperative LLD and restore femoral offset.

Prevalences and Characteristics of Trichuris Spp. Infection in Sheep in Pastoral Areas of the Tianshan, Xinjiang, China.

Introduction: Nematodes of the Trichuris genus are commonly reported parasites that can cause trichuriasis in many animals, which leads to inflammation, intestinal bleeding and reductions of productivity in livestock. Knowledge of the prevalence of Trichuris infestation in the Tianshan ovine population and of the nematode species parasitising the population is not exhaustive, and this study aimed to expand the knowledge. Material and Methods: A total of 1,216 sheep slaughtered in five pasture areas in the Tianshan Mountains of Xinjiang were investigated and a phylogenetic analysis based on the mitochondrial cox1 gene was performed to clarify the genetic relationships of the various Trichuris species. Results: Sheep totalling 1,047 were infected with Trichuris spp. establishing the rate at 86.1%. Using a morphological protocol, six documented and one undefined species were identified, namely T. gazellae, T. lani, T. ovina, T. longispiculus, T. concolor, T. discolor and Trichuris sp. Among them, T. gazellae and T. lani were the dominant species, accounting for 34.5% and 31.0% of Trichuris spp., respectively. Phylogenetic analysis divided the detected species of Trichuris spp. into two genetic clades (clade I and clade II). The six documented species that can infect sheep and the undefined species were clustered into clade I, with inter- and intra-species genetic diversity apparent. Conclusion: This survey described in detail the morphological characteristics of six known and one undefined species of Trichuris, which not only enriched the taxonomic information on record regarding Trichuris spp., but also provided valuable epidemiological data for the prevention and control of trichuriasis in sheep.

Significantly Enhancing the Single-Molecule-Magnet Performance of a Dinuclear Dy(III) Complex by Utilizing an Asymmetric Auxiliary Organic Ligand.

In this work, we employed an asymmetric auxiliary organic ligand (1,1,1-trifluoroacetylacetone, Htfac) to further regulate the magnetic relaxation behavior of series of Dy2 single-molecule magnets (SMMs) with a N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2L) ligand. Fortunately, an air-stable Dy2 complex, [Dy2(L)2(tfac)2] (1; Htfac = 1,1,1-trifluoroacetylacetone) was obtained at room temperature. A structural analysis indicated that some Dy-O or Dy-N bond lengths for 1 are not in the range of those for the complexes [DyIII2(L)2(acac)2]·2CH2Cl2 (Dy2-acac; Hacac = acetylacetone) and [DyIII2(L)2(hfac)2] (Dy2-hfac; Hhfac = hexafluoroacetylacetone), although the electron-withdrawing ability of tfac- is stronger than that of acac- but weaker than that of hfac-. Additionally, the Dy-O3/O3a (the two O atoms bridged to DyIII ions) bond lengths are also affected by the asymmetrical Htfc ligand. This indicated that the charge distribution of the coordination atoms around DyIII has been modified in 1, which leads to the fine-tuning of the magnetic relaxation behavior of 1. Magnetic studies indicated that the values of effective energy barrier (Ueff) for 1 and its diluted sample (2) are 234.8(3) and 188.0(6) K, respectively, which are both higher than the reported value of 110 K for the complex Dy2-hfac. More interestingly, 1 exhibits a magnetic hysteresis opening when T < 2.5 K at zero field, while the hysteresis loops of 2 are closed at a zero dc field. This discrepancy is due to the weak intramolecular exchange coupling in 2, which cannot overcome the QTM of the single DyIII ion. Ab initio calculations for 1 revealed that the charge distributions of the coordination atoms around DyIII ions were regulated and the intramolecular exchange coupling was indeed improved when the asymmetrical Htfc was employed as a ligand for the synthesis of this kind of Dy2 SMM.

Influence of the Different Types of Auxiliary Noncarboxylate Organic Ligands on the Topologies and Magnetic Relaxation Behavior of Zn-Dy Heterometallic Single Molecule Magnets.

In this work, we first synthesized a Zn-Dy complex, [Zn6Dy2(L)6(tea)2(CH3OH)2]·6CH3OH·8H2O (H2L = N-3-methoxysalicylidene-2-amino-3-hydroxypyridine, teaH3 = triethanolamine, 1), by employing H2L, anhydrous ZnCl2, and Dy(NO3)3·5H2O reacting with auxiliary ligand teaH3 in the mixture of CH3OH and DMF. When teaH3 and the solvent CH3OH in the reaction system of 1 were replaced by the auxiliary ligand 2,6-pyridinedimethanol (pdmH2) and the solvent MeCN, another Zn-Dy complex, [Zn4Dy4(L)6(pdm)2(pdmH)4]·10CH3CN·5H2O (2), was obtained. For 1, its crystal structure can be viewed as a dimer of two Zn3DyIII units. However, for 2, four DyIII form a zigzag arrangement, and each of its terminals linked two ZnII ions. Interestingly, although the structural topologies of 1 and 2 are different, the coordination geometries of DyIII in 1 and 2 are all triangular dodecahedron (TDD-8). The difference is that the continuous shape measure (CShM) values of DyIII in 1 are larger than the corresponding values in 2. Magnetic investigation revealed that the diluted sample 1@Y exhibits two magnetic relaxation processes, while 2 only exhibits a single relaxation process. Ab initio calculations indicated that, in the crystal lattice of 1, two complexes exhibiting slightly different CShM values of DyIII result in the double relaxation behavior of 1@Y. However, for 2, one of two DyIII fragments possesses a fast quantum tunneling of magnetization (QTM), resulting in its magnetic process presented at T < 1.8 K, so 2 exhibits single relaxation behavior. More importantly, the theoretical calculations also clearly indicated that the weak ligation at equatorial sites of DyIII in 1 and 2 ensure 1@Y and 2 possess SMM behavior, although the coordination geometry of DyIII (TDD-8) in 1 and 2 severely deviates from the ideal polyhedron and its axial symmetry is low.

Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.

INTRODUCTION: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study. METHODS: BCPP was designed to evaluate the impact of prevention interventions on HIV incidence in 30 communities in Botswana. We followed a longitudinal cohort of newly identified and known HIV-positive persons not on antiretroviral therapy (ART) identified through community-based testing activities through BCPP and referred with appointments to local HIV clinics in 15 intervention communities. Those who did not keep the first or follow-up appointments were tracked and traced through phone and home contacts. Improvements to service delivery models in the intervention clinics were also implemented. RESULTS: A total of 3,657 newly identified or HIV-positive persons not on ART were identified and referred to their local HIV clinic; 90% (3,282/3,657) linked to care and of those, 93% (3,066/3,282) initiated treatment. Near the end of the study, 221 persons remained >90 days late for appointments or missing. Tracing efforts identified 54/3,066 (2%) persons who initiated treatment but died, and 106/3,066 (3%) persons were located and returned to treatment. At study end, 61/3,066 (2%) persons remained missing and were never reached. Overall, 2,951 (98%) persons living with HIV (PLHIV) who initiated treatment were still alive, retained in care and still receiving ART out of the 3,001 persons alive at the end of the study. Of those on ART, 2,854 (97%) had current VL results and 2,784 (98%) of those were virally suppressed at study end. CONCLUSIONS: This study achieved high rates of linkage, treatment initiation, retention and VL coverage and suppression in a cohort of newly identified and known PLHIV not on ART. Tracking and tracing interventions effectively identified those persons who needed more resource intensive follow-up. The interventions implemented to improve service delivery and data quality may have also contributed to high linkage and retention rates. Clinical trial number: NCT01965470.

Effects of progressive resistance training for early postoperative fast-track total hip or knee arthroplasty: A systematic review and meta-analysis.

Progressive resistance training (PRT) is one of the most commonly used exercise methods after joint replacement, while its effectiveness and safety are still controversial. Therefore, it's vital to investigate the effect of PRT on muscle strength and functional capacity early postoperative total hip arthroplasty (THA) or total knee arthroplasty (TKA). Relevant studies were identified via a search of Medline, Web of science and Cochrane Library from 2002 to 12 May 2020. Fifteen of 704 studies which comprised 6 THAs and 8 TKAs, involving 1021 adult patients were eligible for inclusion in the meta-analysis. There were no significant differences between the two groups after TKA in the 6-min walk test (6-WMT) within 1 month (95% CI = -0.41, 1.53), within 3 months (95% CI = -0.27, 0.76), within 12 months (95% CI = -0.29, 0.66); climb performance in seconds (s) (SCP), leg extension power, timed up and go test in seconds (s) (TUG) within 1 month (95% CI = -1.75, 0.77), within 3 months (95% CI = -0.48, 0.33), within 12 months (95% CI = -0.44, 0.35), sit to stand, number of repetitions in 30s (ST). There was no difference in the incidence of adverse events (95% CI = -0.01, 0.10). Similarly, two groups were also no obvious distinction after THA in the 6-WMT, SCP, Leg extension power, ST. PRT early after THA or TKA did not differ significantly from SR in terms of functional capacity, muscle strength recovery and incidence of adverse events. PRT is one of the options for rapid rehabilitation after joint replacement.

Activation and blockade of dorsal hippocampal serotonin4 receptors produce antidepressant effects in the hemiparkinsonian rats.

Depression is a common non-motor symptom in Parkinson's disease (PD). Although serotonin4 (5-HT4) receptors and the dorsal hippocampus (dHIP) are regarded to be involved in the depression, the mechanism underlying the effects of 5-HT4 receptors in the dHIP on PD-related depression should be further investigated. In the present study, unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB) increased the expressions of 5-HT4 receptors and its co-localization with glutamate neurons in the CA1, CA3 and dentate gyrus. Additionally, MFB lesions induced depressive-like behaviors in the sucrose preference and forced swimming tests. The activation or blockade of dHIP 5-HT4 receptors produced antidepressant effects in the MFB lesioned rats but not in control rats. Neurochemical results showed no changes of monoamines levels in the striatum, medial prefrontal cortex (mPFC), lateral habenula (LHb), and ventral hippocampus (vHIP) in control rats after intra-dHIP injection of 5-HT4 receptors agonist BIMU8 (26 µg/rat), antagonist GR 113808 (16 µg/rat) or GR 113808/BIMU8 (26 µg/16 µg/rat). But in the lesioned rats, BIMU8, GR113808 or GR 113808/BIMU8 injection increased dopamine levels in the striatum, mPFC, LHb, and vHIP and increased 5-HT levels in the LHb. Intra-dHIP injection of GR 113808 or GR 113808/BIMU8 also increased the noradrenaline levels in the mPFC and LHb. All these results suggest that activation or blockade dHIP 5-HT4 receptors produce antidepressant effects in the hemiparkinsonian rats, which may be related to the upregulation of 5-HT4 receptors in the dHIP and the changes of monoamines in the limbic and limbic-related brain regions.

Iron Overload Induces Apoptosis and Cytoprotective Autophagy Regulated by ROS Generation in Mc3t3-E1 Cells.

Iron overload has been found very common in diseases such as hereditary hemochromatosis, thalassemia, and sickle cell disease and in healthy postmenopausal women. Recent studies have shown that iron overload is considered an independent risk factor for osteoporosis. Studies have demonstrated that iron overload could induce apoptosis and inhibit viability in osteoblasts. However, the underlying mechanism still remains poorly understood. The purpose of the present study is to investigate possible mechanism of iron overload-induced apoptosis, and the roles autophagy and reactive oxygen species (ROS) played under iron overload conditions. Ferric ammonium citrate (FAC) (100-1600 µM) was utilized as iron donor to induce iron overload conditions. Intracellular iron concentration was measured using Iron Assay Kit. The viability was assessed by CCK-8 assay. Cell apoptosis was examined using Annexin V-FITC/PI staining with a flow cytometry, and levels of Bax, Bcl-2, cleaved caspase-3, and cleaved PARP were evaluated with Western blot. Cell autophagy was detected by evaluating LC3 with immunofluorescence and Western blot. The expressions of Beclin-1 and P62 were also assessed with Western blot. The intracellular ROS level was evaluated using a DCFH-DA probe with a flow cytometry, and NADPH oxidase 4 (Nox4) expressions were assessed with Western blot. Our results showed that FAC increased intracellular iron concentration and significantly inhibited cell viability. Furthermore, iron overload induced apoptosis and autophagy in osteoblast cells. What's more, pretreatment with autophagy inhibitor chloroquine (CQ) enhanced iron overload-induced osteoblast apoptosis via the activation of caspases. Moreover, iron overload increased ROS production and Nox4 expression. Inhibition of autophagy increased ROS production, and scavenging of ROS by antioxidant N-Acetyl-L-cysteine (NAC) inhibited caspases activity and rescued iron overload-induced apoptosis. These results suggested that autophagy exerted cytoprotective effect, and scavenging excessive intracellular ROS could be a novel approach for the treatment of iron overload-induced osteoporosis.

Activation and Blockade of Serotonin-4 Receptors in the Lateral Habenula Produce Antidepressant Effects in the Hemiparkinsonian Rat.

BACKGROUND: The 5-hydroxytryptamine (5-HT) neurotransmitter system and lateral habenula (LHb) are involved in the regulation of depression, while the mechanisms remain to be clarified. OBJECTIVES: The effects and possible mecha-nism underlying activation or blockade of 5-HT4 receptors (5-HT4Rs) in the LHb in depression were investigated by behavioral and neurochemical methods based on a Parkinson's disease (PD) rat model. METHOD: 6-Hydroxydopamine (6-OHDA) was injected unilaterally into the substantia nigra pars compacta to establish the PD rat model. The depressive-like behaviors were measured by the forced swimming test (FST) and sucrose preference test (SPT). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by a neurochemical method. RESULTS: The 6-OHDA lesions increased the immobility time in the FST and decreased the sucrose consumption in the SPT, suggesting the induction of depressive-like behaviors. Intra-LHb injection of BIMU-8 (5-HT4R agonist) or GR113808 (5-HT4R antagonist) produced antidepressant effects in the lesioned rats. Intra-LHb injection of BIMU-8 significantly increased the DA levels in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHip), increased the 5-HT level in the mPFC and decreased the NA level in the vHip only in the lesioned rats, while intra-LHb injection of GR113808 changed DA, NA and 5-HT levels in the mPFC, LHb and vHip in both sham and the lesioned rats. CONCLUSIONS: All these results suggest that activation or blockade of the LHb 5-HT4Rs produce antidepressant effects in the 6-OHDA-lesioned rats, which are related to the changes of monoamines in the limbic and limbic-related regions.

Case Report: Opportunities for Treatment of Severe COVID-19 Patients-Lessons From a Death Case.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the incidence of coronavirus disease (COVID-19) increases each day. To date, there is no specific anti-SARS-CoV-2 drug. The usual approach to treating COVID-19 is treating its symptoms. However, this approach is limited by the different conditions of each area. We treated a 57-year-old man who was initially diagnosed with a severe type of the infection, but he progressed to a critical condition and eventually died. We learned valuable lessons from this case. The first lesson is the need to use immediate invasive mechanical ventilation if there is no obvious improvement after using non-invasive ventilation for several hours, which directly affects the prognosis. Another lesson is the risk involved in transferring severe COVID-19 patients. In the process of transfer, various threats may be encountered at any time. Thus, accurate assessment of the patient's condition and strict medical conditions are highly required. During the patient's 25-day treatment, we performed cardiopulmonary resuscitation twice. Currently, many patients require invasive mechanical ventilation and transfer to a superior hospital. We hope our findings will provide some advice and help for treating severe and critical COVID-19 cases.

A study on the mechanism of Wnt inhibitory factor 1 in osteoarthritis.

INTRODUCTION: In our study we aimed to investigate the mechanism of Wnt inhibitory factor 1 (WIF1) on regulating chondrocyte proliferation and apoptosis via reactive oxygen species (ROS) and the Wnt/ßcatenin signaling pathway in osteoarthritis (OA). MATERIAL AND METHODS: Osteoarthritis chondrocytes were treated with interleukin 1ß (IL-1ß) to simulate an inflammatory condition. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied for detecting WIF1 expression in OA chondrocytes. MTT assay and flow cytometry were carried out to analyze the cell proliferation and apoptosis. Content of ROS was detected using flow cytometry, and activity of the Wnt/ßcatenin signaling pathway was detected using immunofluorescence, western blot and luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expression of apoptosis-related proteins and secretion of matrix metalloproteinases (MMPs). RESULTS: WIF1 expression in OA chondrocytes was significantly lower than in normal chondrocytes. After WIF1 cDNA transfection, the aberrantly high ROS level in OA chondrocytes was down-regulated, which led to the increase of proliferation and reduction of apoptosis. The Wnt/ßcatenin signaling pathway was suppressed by WIF1 overexpression and the secretion of MMPs was therefore reduced. CONCLUSIONS: Up-regulation of WIF1 would promote proliferation and suppress apoptosis of OA chondrocytes through eliminating ROS production and reduce secretion of MMPs via blocking the Wnt/ßcatenin signaling pathway.