Inhibiting Heat Shock Protein 90 Attenuates Nucleus Pulposus Fibrosis and Pathologic Angiogenesis Induced by Macrophages via Down-Regulating Cell Migration-Inducing Protein.

Intervertebral disc (IVD) degeneration (IVDD) is usually accompanied by nucleus pulposus (NP) fibrosis and pathologic angiogenesis, which are possibly associated with macrophage infiltration. Previous research indicates a destructive role of macrophages and the protective effect of inhibiting heat shock protein 90 (HSP90) in IVDD. Herein, the effects of inhibiting HSP90 on NP fibrosis and pathologic angiogenesis induced by macrophages were investigated further. Single-cell RNA-sequencing analysis was used to classify fibrotic NP cell (NPC) clusters and healthy NPC clusters in human NP tissues. The fibrotic NPC clusters were possibly associated with angiogenesis-related biological processes. Immunostaining showed the spatial association between blood vessel ingrowth and macrophage infiltration, as well as elevated levels of cell migration-inducing protein (CEMIP) and vascular endothelial growth factor A in severely degenerated human IVD tissues. Particularly, HSP90 inhibitor tanespimycin (17-AAG) ameliorated macrophage-induced fibrotic phenotype of NPCs via inhibiting CEMIP. M2, but not M1, macrophages promoted the pro-angiogenic ability of endothelial cells, which was attenuated by 17-AAG or HSP90 siRNA. Reversing the fibrotic phenotype of NPCs by Cemip siRNA also mitigated the pro-angiogenic effects of M2-conditioned medium-treated NPCs. Moreover, the murine IVDD model supported the 17-AAG-induced amelioration of NP fibrosis and endothelial cell invasion in IVD tissues. In conclusion, inhibiting HSP90 attenuated two interrelated pathologic processes, NP fibrosis and pathologic angiogenesis, induced by macrophages via down-regulating CEMIP.

Stitching interferometry using alternating calibration of positioning and systematic errors.

Stitching interferometry is an essential technique for the non-contact, high-precision measurement of large apertures or complex optical surfaces. However, the accuracy of full-aperture surface reconstruction is significantly compromised by subaperture positioning and systematic errors. To address this challenge, this study introduces a novel stitching interferometry method utilizing alternating calibration of positioning and systematic errors (SIAC). This method calibrates one type of error while maintaining the other constant, and alternates between these processes to effectively decouple the two errors, facilitating accurate phase stitching. Within this calibration framework, an iterative weighted phase stitching model employing vertical projection for estimating overlapping areas was developed to calibrate positioning errors. Additionally, the rotation measurements of a single subaperture, in conjunction with a global fitting approach, were employed to correct reference errors. Numerical simulations have confirmed the efficacy of SIAC in calibrating these errors. Moreover, experimental measurements were performed on both a plane mirror and gullwing aspheres, with the resulting stitched full-aperture phase distributions and cross-testing outcomes affirming the method's accuracy and practicality. This research provides a novel solution for stitching interferometry, enhancing the precision of optical surface measurements.

Pooling sputum samples for the Xpert MTB/RIF assay: a practical screening strategy for highly infectious tuberculosis cases.

The Xpert MTB/RIF test (Xpert) can help in the accurate screening of tuberculosis, however, its widespread use is limited by its high cost and lack of accessibility. Pooling of sputum samples for testing is a strategy to cut expenses and enhance population coverage but may result in a decrease in detection sensitivity due to the dilution of Mycobacterium tuberculosis (Mtb) by sample mixing. We investigated how the mixing ratio affected the detection performance of Xpert. We used frozen sputum samples that had been kept after individual Xpert assays of the sputa from Mtb-confirmed TB patients and non-TB patients. Our results showed that the overall sensitivity of the Xpert pooling assay remained higher than 80% when the mixing ratio was between 1/2 and 1/8. When the mixing ratio was raised to 1/16, the positive detection rate fell to 69.0%. For patients with either a high sputum Mtb smear score ≥ 2+, a time-to-positive culture ≤ 10 days, or an Xpert test indicating a high or medium abundance of bacteria, the pooling assay positivity rates were 93.3%, 96.8%, and 100% respectively, even at a 1/16 mixing ratio. For participants with cavities and cough, the pooling assay positivity rates were 86.2% and 90.0% at a 1/8 ratio, higher than for those without these signs. Our results show that the Xpert pooled assay has a high overall sensitivity, especially for highly infectious patients. This pooling strategy with lower reagent and labor costs could support TB screening in communities with limited resources, thereby facilitating reductions in the community transmission and incidence of TB worldwide.

Regioselective One-Step Cyclization and Aromatization towards Directly Amino-Functionalized Covalent Organic Framework with Stable Benzodiimidazole Linkage.

The compatibility of crystallinity, stability, and functionality in covalent organic frameworks (COFs) is challenging but significant in reticular chemistry and materials science. Herein, it is presented for the first time a strategy to synthesize directly amino-functionalized COF with stable benzodiimidazole linkage by regioselective one-step cyclization and aromatization. Bandrowski's base with two types of amino groups is used as a unique monomer, providing not only construction sites for the material framework through specific region-selective reaction, but also amino active sites for functionality, which is usually difficult to achieve directly in COF synthesis because amino groups are the participants in COF bonding. In addition, the aromatic benzodiimidazole rings and the large conjugated system of the product effectively improve the crystallinity and stability, so that the as-prepared BBCOF remains unchanged in both acid and base solutions, which is obviously better than the conventional imine-linked COF. Impressively, the significantly enhanced conjugation degree by the benzodiimidazole structure also endows BBCOF with an efficient photocatalytic reduction of uranyl ion, with removal rate as high as 96.6% in single-ion system and 95% in multi-ion system. This study is of great importance to the design and synthesis of functional COFs with a commendable trade-off among crystallinity, stability, and functionality.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Proximal femoral bionic nail (PFBN)-an innovative surgical method for unstable femoral intertrochanteric fractures.

PURPOSE: Intertrochanteric femoral fractures (IFF) are one of the most common traumatic conditions, but there are no established treatment methods for this condition due to implant failure and re-operation rates. The proximal femoral bionic nail (PFBN), which is a new design of the cephalomedullary nail, was developed by our team. The objective of this study was to assess the clinical and radiographic outcomes of PFBN in patients with unstable IFF. METHODS: From October 2020 to August 2021, 12 patients diagnosed with unstable IFF (31-A2, 3) were treated with PFBN at the Third Hospital of Hebei Medical University. We evaluated the clinical therapeutic effects of this treatment by measuring peri-operative indicators and post-operative complications. Clinical outcomes, specific radiographic parameters, and post-operative complications were collected and analyzed within the first post-operative year. RESULTS: The average age of the patients was 72.4 ± 16.1 years (five males and seven females). The mean operation time was 90.4 ± 16.0 min, whereas the operation time of 31-A2 fractures (83.1 ± 12.2 min) was shorter than that of 31-A3 fractures (105.0 ± 12.9 min) (p < 0.05). The blood loss was 175 ml (range: 50 to 500 ml), and the length of hospitalization was 10.0 ± 1.9 days. The prognosis evaluation was assessed at three, six and 12 months after the operation; for these time points, the Harris hip scores were 69.6 ± 4.1, 77.8 ± 3.8, and 82.6 ± 4.6, respectively, and the Parker-Palmer scores were 5.3 (5.0, 7.0), 6.3 (5.3, 7.0), and 7.8 (7.0, 8.0), respectively. CONCLUSION: PFBN has shown advantages in the treatment of unstable IFF (particularly in geriatric patients) and possesses both stability and safety. This innovative method may provide a new option for treating unstable IFFs.

The Wheat Annexin TaAnn12 Plays Positive Roles in Plant Disease Resistance by Regulating the Accumulation of Reactive Oxygen Species and Callose.

(1) Annexins are proteins that bind phospholipids and calcium ions in cell membranes and mediate signal transduction between Ca2+ and cell membranes. They play key roles in plant immunity. (2) In this study, virus mediated gene silencing and the heterologous overexpression of TaAnn12 in Arabidopsis thaliana Col-0 trials were used to determine whether the wheat annexin TaAnn12 plays a positive role in plant disease resistance. (3) During the incompatible interaction between wheat cv. Suwon 11 and the Puccinia striiformis f. sp. tritici (Pst) race CYR23, the expression of TaAnn12 was significantly upregulated at 24 h post inoculation (hpi). Silencing TaAnn12 in wheat enhanced the susceptibility to Pst. The salicylic acid hormone contents in the TaAnn12-silenced plants were significantly reduced. The overexpression of TaAnn12 in A. thaliana significantly increased resistance to Pseudomonas syringae pv. tomato DC3000, and the symptoms of the wild-type plants were more serious than those of the transgenic plants; the amounts of bacteria were significantly lower than those in the control group, the accumulation of Reactive Oxygen Species (ROS)and callose deposition increased, and the expression of resistance-related genes (AtPR1, AtPR2, and AtPR5) significantly increased. (4) Our results suggest that wheat TaAnn12 resisted the invasion of pathogens by inducing the production and accumulation of ROS and callose.

Extracellular matrix in intervertebral disc: basic and translational implications.

Intervertebral disc (IVD) degeneration (IVDD) is the most common spinal disorder, which can lead to the symptoms of neck pain or low back pain. In healthy mature IVD tissues, extracellular matrix (ECM) complex possesses favorable biochemical and biomechanical properties, withstanding compression and torsion forces. IVD cells and ECM associate with each other to form a coordinated functional system. IVD cells are the main producers of ECM components, while ECM could modulate the viability and phenotype of IVD cells via direct interactions or indirect regulations. However, with the process of IVDD and ageing, ECM of IVD undergoes content loss and structure degeneration. Moreover, the accumulation of catabolic products may further deteriorate the IVD microenvironment. A better understanding of the physiology and the pathology of ECM within the IVD provides new insight into potential IVD regeneration strategies. Natural ECM components, functional motifs, or mimetic peptides are widely used in IVD repair by not only restoring structural support but also regulating cell fate and tissue microenvironment. Herein, we reviewed recent advances in the involvement of ECM in IVD health and disease, with an emphasis on ECM composition and organization, cell-matrix interactions, pathological ECM degradation, and promising matrix-based biomaterials for IVD regeneration.

PCL scaffold combined with rat tail collagen type I to reduce keratocyte differentiation and prevent corneal stroma fibrosis after injury.

The cornea is one of the major refractive eye components and could be easily injured. An ineffective healing of corneal stromal wound may cause fibrosis and even loss of vision. Therefore, it is pivotal to prevent corneal fibrosis after injury. In this study, a poly (ε-caprolactone) (PCL) microfibrous scaffold infused with rat tail collagen type I was fabricated to obtain a 3D composite material. Physical and biological properties of PCL/collagen scaffold were evaluated, the effect of PCL/collagen scaffold on the proliferation and differentiation of limbal stromal stem cells (LSSCs) were detected in vitro, the differentiation of keratocytes as well as the expression and arrangement of extracellular matrix (ECM) influenced by PCL/collagen scaffold were investigated in vivo. RNA-sequencing on normal and injured corneas was carried out to find out the differential enriched pathways and gene expression. We discovered that the PCL/collagen scaffold simulated the stromal structure with properties that were most similar to the native cornea, the PCL/collagen scaffold exhibited good mechanical and biological properties. We also observed that the PCL/collagen scaffold reduced keratocyte differentiation. Injured corneas treated with PCL/collagen scaffold exhibited more regular collagen distribution and less fibroblasts and myofibroblasts distribution. By RNA-sequencing, we observed that in injured group, ECM-related pathway was enriched and several ECM-related genes were up-regulated. This study provides evidence that application of PCL/collagen scaffold could be a new therapeutic strategy for corneal injury.

Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine.

BACKGROUND: Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce. METHODS: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis. RESULTS: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders. CONCLUSIONS: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.

PAHs bound to submicron particles in rural Chinese homes burning solid fuels.

Inhalation exposure to polycyclic aromatic hydrocarbons (PAHs) from indoor solid fuel combustion poses a high health risk, and PAHs bound to particles with smaller sizes (e.g., PM1.0, aerodynamic diameter ≤ 1.0 µm) should be of particular concern since they can penetrate deep into pulmonary alveoli. However, PAHs bound to PM1.0 was less studied compared with PAHs in total suspended particles or PM2.5. In this study, multiple provincial field measurements were conducted to investigate 28 PAHs bound to PM1.0 in rural Chinese homes. Daily averaged PM1.0-PAH28 concentrations ranged from 27 ng/m3 to 3795 ng/m3 (median: 233 ng/m3) and from 10 ng/m3 to 2978 ng/m3 (median: 87 ng/m3) in indoor and outdoor air, respectively. Higher concentrations were found in northern China in winter due to increased solid fuels consumption for space heating. The ambient pollution was lower during the non-heating season in Eastern China, where clean energy was preferred. Highly toxic congeners were more abundant in indoor air compared with outdoor air. The results of source apportionment revealed that solid fuel combustion was the primary contributor to rural household PM1.0-PAHs, but other sources such as vehicles cannot be overlooked. The transition to cleaner energy can reduce the indoor PM1.0-PAH28 and BaPeq-28 concentrations by 87% and 98%, respectively, and more efficient reduction was observed for highly toxic congeners. The estimated Incremental Lifetime Cancer Risk (ILCR) based on PM1.0-PAH28 ranged from 4.6 × 10-5 to 3.4 × 10-2, far exceeding the acceptable level of 10-6. Over 60% of the ILCR could be attributed to inhalation exposure during childhood and adolescence.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Activation of HSP70 impedes tert-butyl hydroperoxide (t-BHP)-induced apoptosis and senescence of human nucleus pulposus stem cells via inhibiting the JNK/c-Jun pathway.

The endogenous repair failure of degenerated intervertebral disk (IVD) is highly related to the exhaustion of nucleus pulposus stem cells (NPSCs). Excessive oxidative stress could induce apoptosis and senescence of NPSCs, thus, declining the quantity and quality of NPSCs. Heat shock protein 70 (HSP70) is a family of cytoprotective and antioxidative proteins. However, there is no report on the protective effects of HSP70 on oxidative stress-induced NPSC impairments and underlying mechanisms. In the present study, we treated NPSCs with tert-butyl hydroperoxide (t-BHP) in vitro to simulate an oxidative stress condition. HSP70 inducer TRC051384 was used to evaluate the cytoprotective effects of HSP70. The results suggested that HSP70 impeded t-BHP-mediated cell viability loss and protected the ultrastructure of NPSCs. Moreover, t-BHP could induce mitochondrial apoptosis and p53/p21-mediated senescence of NPSCs, both of which were significantly inhibited in HSP70 activation groups. Excessive oxidative stress and mitochondrial dysfunction reinforced each other and contributed to the cellular damage processes. HSP70 decreased reactive oxygen species (ROS) production, rescued mitochondrial membrane potential (MMP) collapse, and blocked ATP depletion. Finally, our data showed that HSP70 downregulated the JNK/c-Jun pathway. Taken together, activation of HSP70 could protect against t-BHP-induced NPSC apoptosis and senescence, thus, improving the quantity and quality of NPSCs. Therefore, HSP70 may be a promising therapeutic target for IVD degeneration.

Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients.

Suicide is a tremendous threat to global public health, and a large number of people who committed suicide suffered the pain of mental diseases, especially major depressive disorder (MDD). Previous study showed that ketamine could reduce suicidal ideation (SI), potentially by improving the impaired working memory (WM). The objective of current study was to illuminate the relationship between WM and SI in MDD with repeated ketamine treatment. MDD patients with SI (n = 59) and without SI (n = 37) completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Day 1, 3, 5, 8, 10 and 12). The severity of depressive symptoms, SI and WM were assessed at baseline, day 13 and day 26. We found that WM was significantly improved after 6 ketamine infusions (F = 161.284, p = 0.009) in a linear mixed model. Correlation analysis showed that the improvement of depressive symptom was significantly associated with WM at baseline (r = - 0.265, p = 0.042) and the reduction in SSI-part I was related to the change of WM (r = 0.276, p = 0.034) in the MDD patients with SI. Furthermore, Logistic regression analysis showed that improvement in WM might predict the anti-SI response of ketamine. Our findings suggest that the improvement of working memory may partly account for the anti-SI effect of ketamine, and intervention of improving working memory function may be capable of reducing suicidal ideation.

Mitochondria-targeted accumulation of oxygen-irrelevant free radicals for enhanced synergistic low-temperature photothermal and thermodynamic therapy.

BACKGROUND: Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. METHODS AND RESULTS: In this work, a core-shell nanoplatform with an appropriate size composed of arginine-glycine-aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. CONCLUSIONS: The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors.

Amplification of oxidative stress with lycorine and gold-based nanocomposites for synergistic cascade cancer therapy.

BACKGROUND: Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy. METHODS AND RESULTS: A novel nanocomposite, composed of folic acid (FA) modified mesoporous silica-coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice. CONCLUSION: All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.

The influence of the steep medial posterior tibial slope on medial meniscus tears in adolescent patients: a retrospective case-control study.

BACKGROUND: Several studies have demonstrated a relationship between the posterior tibial slope (PTS) and meniscal tears in adults. However, little is known about the association between the PTS of the adolescents and medial meniscal tears (MMT). The purpose of this study was to evaluate the association between the PTS and MMT in adolescents, and to determine the optimal cut-off values of PTS for discriminating between the MMT and the control groups. METHODS: Between January 2018 and January 2020, a retrospective case-control study was performed. In this study, isolated MMT adolescent patients with no ligamentous injuries were matched by age and sex to a control group of radiologically normal images. The PTS was defined as the angle between the perpendicular line to proximal tibial cortex (PTC) and the tangent line along the tibial plateau. Then, both the medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS) were measured by plain radiographs on the lateral views. In addition, the optimal cut-off values of PTS were determined by the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of seventy-two patients who met the inclusion criteria were enrolled in the final analysis (36 patients with isolated MMT, 36 controls). The MPTS was greater in the knees with isolated MMT (10.7° ± 2.1°) than that of the control group (8.8° ± 1.7°), showing significant difference (P<0.001). However, there was no significant difference regarding the LPTS between the isolated MMT and controls (11.5 ± 3.4 vs 10.9 ± 2.6, p>0.05). In the ROC curve analysis, the calculated cutoff value of the MPTS discriminating between the groups was 10.3°, with a sensitivity of 73.3% and specificity of 78.9%. CONCLUSIONS: This study demonstrated that steep MPTS is associated with MMT, and MPTS≥10.3° was identified to be a risk factor for MMT in adolescents.

Long-term outcomes after partial patellectomy in comminuted fractures - a clinical study.

PURPOSE: The purpose of this study was to evaluate the long-term clinical and radiographic outcomes of partial patellectomy (PP) in patients with patella comminuted distal pole fractures. METHODS: Seventeen patients who were diagnosed with patella comminuted distal pole fractures and underwent PP procedures were retrospectively included between January 1995 and January 2005. We collected patient demographics and data on the mechanism of injury, time to surgery, fracture type, follow-up time, and post-operative complications (infection, patellofemoral arthritis, and stiffness). At the final follow-up, functional outcome was evaluated by the range of motion (ROM) and the Bostman Scoring System. Quadriceps strength was evaluated by using an isokinetic dynamometer to measure peak torque, and patellar height was evaluated by the Insall-Salvati (IS) ratio in lateral knee radiographs. The average follow-up period was 14.6 years (range, 11-19 years). RESULTS: We analyzed 17 patients (AO/OTA 34-A1), with an average age of 59.8 years (range, 43-76 years). According to the Bostman grading scales, final functional outcomes were excellent in 11 (64.7%) and good in six (35.3%) patients. All patients had full knee extension, and the average ROM was 125.1° (range, 121.4-129.3°). The average peak torque of the injured knee was 103.2 ± 9.7 Nm, and that of the uninjured opposite side was 108.3 ± 7.6 Nm, with no significant difference (p > 0.05). Furthermore, no postoperative complications, such as infection, posttraumatic osteoarthritis, or stiffness, were observed. Compared to the uninjured knee, the IS ratio of the injured knee was 0.76 ± 0.13, indicating that the patellar height was decreased, which meant patella baja. CONCLUSIONS: The PP procedure for patella comminuted distal pole fractures is a safe, simple, and reliable technique that can provide good long-term clinical outcomes even with decreased patellar height and could be a satisfactory alternative treatment option when anatomical reduction is difficult.

Three-dimensional-printed intercalary prosthesis for the reconstruction of large bone defect after joint-preserving tumor resection.

BACKGROUND: Joint-preserving intercalary tumor resection can result in better proprioception and a more normal joint function after reconstruction. However, most reported reconstruction techniques are usually associated with frequent complications. Therefore, the approach of reconstruction following joint-preserving tumor resection warrants further study. METHODS: Between September 2016 and October 2018, 12 patients with metaphyseal malignant bone tumors around the knee joint were treated by joint-preserving intercalary resections with the aid of three-dimensional (3D)-printed osteotomy guide plates and reconstructions using 3D-printed intercalary prostheses. We assessed the accuracy of the resection by comparing the cross sections at the resection plane with 3D-printed matching surface of the prostheses. The functional outcomes, complications and oncological status were also evaluated. RESULTS: All patients were observed for 7 to 32 months with an average follow-up of 22.5 months. The achieved resection was accurate, with accurate matching between the residual bone and prosthesis. The mean MSTS score was 28 (range, 26-30). Superficial infection occurred in two patients. Local recurrence was observed in one patient, while pulmonary metastasis was identified in one patient. CONCLUSIONS: The personalized osteotomy guide plate and prosthesis based on 3D printing technique facilitate joint-preserving tumor resection and functional reconstruction. However, longer follow-up and larger sample size are required to clarify its long-term outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.