Significant race and gender differences in anterior cruciate ligament tibial footprint location: a 3D-based analysis.

BACKGROUND: The aim of the present study was to identify potential race- or gender-specific differences in anterior cruciate ligament (ACL) tibial footprint location from the tibia anatomical coordinate system (tACS) origin, investigate the distances from the tibial footprint to the anterior root of the lateral meniscus (ARLM) and the medial tibial spine (MTS), determine how reliable the ARLM and MTS can be in locating the ACL tibial footprint, and assess the risk of iatrogenic ARLM injuries caused by using reamers with various diameters (7-10 mm). PATIENTS AND METHODS: Magnetic resonance images of 91 Chinese and 91 Caucasian subjects were used for the reconstruction of three-dimensional (3D) tibial and ACL tibial footprint models. The anatomical coordinate system was applied to reflect the anatomical locations of scanned samples. RESULTS: The average anteroposterior (A/P) tibial footprint location was 17.1 ± 2.3 mm and 20.0 ± 3.4 mm in Chinese and Caucasians, respectively (P < .001). The average mediolateral (M/L) tibial footprint location was 34.2 ± 2.4 mm and 37.4 ± 3.6 mm in Chinese and Caucasians, respectively (P < .001). The average difference between men and women was 2 mm in Chinese and 3.1 mm in Caucasians. The safe zone for tibial tunnel reaming to avoid ARLM injury was 2.2 mm and 1.9 mm away from the central tibial footprint in the Chinese and Caucasians, respectively. The probability of damaging the ARLM by using reamers with various diameters ranged from 0% for Chinese males with a 7 mm reamer to 30% in Caucasian females with a 10 mm reamer. CONCLUSIONS: The significant race- and gender-specific differences in the ACL tibial footprint should be taken in consideration during anatomic ACL reconstruction. The ARLM and MTS are reliable intraoperative landmarks for identifying the tibial ACL footprint. Caucasians and females might be more prone to iatrogenic ARLM injury. LEVEL OF EVIDENCE: III, cohort study. TRIAL REGISTRATION: This study has been approved by the ethical research committee of the General Hospital of Southern Theater Command of PLA under the code: [2019] No.10.

Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells.

The mammalian target of rapamycin (mTOR) pathway, which plays a critical role in regulating cellular growth and metabolism, is aberrantly regulated in the pathogenesis of a variety of neoplasms. Here we demonstrate that dual mTORC1/mTORC2 inhibitors OSI-027 and PP242 cause catastrophic macropinocytosis in rhabdomyosarcoma (RMS) cells and cancers of the skin, breast, lung, and cervix, whereas the effects are much less pronounced in immortalized human keratinocytes. Using RMS as a model, we characterize in detail the mechanism of macropinocytosis induction. Macropinosomes are distinct from endocytic vesicles and autophagosomes in that they are single-membrane bound vacuoles formed by projection, ruffling, and contraction of plasma membranes. They are positive for EEA-1 and LAMP-1 and contain watery fluid but not organelles. The vacuoles then merge and rupture, killing the cells. We confirmed the inhibition of mTORC1/mTORC2 as the underpinning mechanism for macropinocytosis. Exposure to rapamycin, an mTORC1 inhibitor, or mTORC2 knockdown alone had little or reduced effect relative to the combination. We further demonstrate that macropinocytosis depends on MKK4 activated by elevated reactive oxygen species. In a murine xenograft model, OSI-027 reduced RMS tumor growth. Molecular characterization of the residual tumors was consistent with the induction of macropinocytosis. Furthermore, relative to the control xenograft tumors, the residual tumors manifested reduced expression of cell proliferation markers and proteins that drive the epithelial mesenchymal transition. These data indicate a role of mTORC2 in regulating tumor growth by macropinocytosis and suggest that dual inhibitors could help block refractory or recurrent RMS and perhaps other neoplasms and other cancer as well.

A Novel Approach for Cable Tension Monitoring Based on Mode Shape Identification.

Estimation and monitoring of cable tension is of great significance in the structural assessment of cable-supported bridges. For short cables, the traditional cable tension identification method via frequency measurement has large errors due to the influence of complex boundaries, which affect the accuracy of estimation. A new cable tension estimation method based on mode shape identification with a multiple sensor arrangement on the cable can take the influence of boundary conditions into account and its accuracy has been verified. However, it requires more sensors compared to the traditional frequency-based method, which will significantly increase the cost of long-term monitoring in practice. Therefore, a novel approach for cable tension monitoring considering both cost and accuracy is further proposed in this study. The approach adopts multiple sensors to measure the influence of boundary conditions. Then, only a single sensor is required for long-term monitoring of the cable. In this paper, an analytical model of the cable is firstly established. The influence of boundary conditions is calculated, which ensures the accuracy of mode shape identification. Furthermore, a field experiment is carried out to verify the effectiveness of the new approach. The results have demonstrated the effectiveness and accurateness of the proposed method in long-term short cable tension monitoring.

High femoral anteversion in osteoarthritic knees, particularly for severe valgus deformity.

OBJECTIVE: Increased femoral anteversion (FA) has been correlated with less varus deformities in osteoarthritic (OA) knees, but the relationship between FA and the degree of valgus deformity in osteoarthritic (OA) knees is still largely unknown. We aimed to thoroughly analyze the distribution of FA in relation to varus or valgus deformities of the lower extremity in OA knees, and to further clarify the relationship between FA and trochlear morphology. METHODS: 235 lower extremities with OA knees were divided into five groups according to the mechanical tibiofemoral angle: excessive valgus (< - 10°), moderate valgus (- 10° to - 3°), neutral (- 3° to 3°), moderate varus (3° to 10°), and excessive varus (> 10°). FA (measured using the posterior condylar axis [pFA] and the transepicondylar axis [tFA]) was measured, and the relationships of FA to the mechanical tibiofemoral angle and femoral trochlear morphology were identified. RESULTS: Excessive FA (pFA ≥ 20°) was observed in 30.2% of all patients and in 58.8% of patients in the excessive valgus group. pFA showed a strong correlation with mechanical tibiofemoral angle (p = 0.018). Both the pFA and the tFA of patients in the excessive valgus group were greater than those in other four groups (all p ≤ 0.037). There were significant correlations between tFA and trochlear parameters, including the sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS) (all p ≤ 0.028). CONCLUSION: High FA is prevalent, particularly in severe valgus knees, and FA is significantly related to the femoral trochlear morphology in OA knees. With the aim of improving the patellofemoral prognosis and complications, high FA should be considered during total knee arthroplasty.

Cutaneous exposure to lewisite causes acute kidney injury by invoking DNA damage and autophagic response.

Lewisite (2-chlorovinyldichloroarsine) is an organic arsenical chemical warfare agent that was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only the result of cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analog phenylarsine oxide (PAO) in a murine model. Both agents caused renal tubular injury, characterized by loss of brush border in proximal tubules and tubular cell apoptosis accompanied by increases in serum creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Interestingly, lewisite exposure enhanced production of reactive oxygen species (ROS) in the kidney and resulted in the activation of autophagic and DNA damage response (DDR) signaling pathways with increased expression of beclin-1, autophagy-related gene 7, and LC-3A/B-II and increased phosphorylation of γ-H2A.X and checkpoint kinase 1/2, respectively. Terminal deoxyribonucleotide-transferase-mediated dUTP nick-end labeling-positive cells were detected in renal tubules along with enhanced proapoptotic BAX/cleaved caspase-3 and reduced antiapoptotic BCL2. Scavenging ROS by cutaneous postexposure application of the antioxidant N-acetyl-l-cysteine reduced lewisite-induced autophagy and DNA damage. In summary, we provide evidence that topical exposure to lewisite causes AKI. The molecular mechanism underlying these changes involves ROS-dependent activation of autophagy and DDR pathway associated with the induction of apoptosis.

Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing EMT in gastric cancer.

BACKGROUND: TSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. However, the role of TSP50 in gastric cancer remains elusive. METHODS: qRT-PCR, western blot were used to determine TSP50 expression in gastric cancer cell lines. Role of TSP50 in proliferation and invasion was examined by BrdU incorporation assay, cell count, wound healing and transwell assay. Immunohistochemistry and western blot were performed to identify the potential mechanisms involved. RESULTS: TSP50 was highly expressed in most of the gastric cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in gastric cancer cells enhanced proliferation and invasiveness, whereas down-regulation of TSP50 by its specific shRNA decreased it. A negative correlation between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination of them improves the prediction for prognosis and lymph node metastasis. Mechanistic studies revealed that overexpression of TSP50 increased the expression of epithelial-to-mesenchymal transition (EMT) markers including Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-κB signaling pathway is involved in the regulatory effects of TSP50 on EMT, migration and invasion in gastric cancer cells. CONCLUSION: TSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-κB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer.

Molecular Mechanism Underlying Pathogenesis of Lewisite-Induced Cutaneous Blistering and Inflammation: Chemical Chaperones as Potential Novel Antidotes.

Lewisite is a potent arsenic-based chemical warfare agent known to induce painful cutaneous inflammation and blistering. Only a few modestly effective antidotes have so far been described in the literature. However, the discovery of effective antidotes for lewisite was hampered by the paucity of the exact molecular mechanism underlying its cutaneous pathogenesis. We investigated the molecular mechanism underlying lewisite-induced cutaneous blistering and inflammation and describe its novel antidotes. On the basis of our initial screening, we used a highly sensitive murine model that recapitulates the known human pathogenesis of arsenicals-induced cutaneous inflammation and blistering. Topically administered lewisite induced potent acute inflammation and microvesication in the skin of Ptch1(+/-)/SKH-1 mice. Even at a very low dose, lewisite up-regulates unfolded protein response signaling, inflammatory response, and apoptosis. These cutaneous lesions were associated with production of reactive oxygen species and extensive apoptosis of the epidermal keratinocytes. We confirmed that activation of reactive oxygen species-dependent unfolded protein response signaling is the underlying molecular mechanism of skin damage. Similar alterations were noticed in lewisite-treated cultured human skin keratinocytes. We discovered that chemical chaperone 4-phenyl butyric acid and antioxidant N-acetylcysteine, which significantly attenuate lewisite-mediated skin injury, can serve as potent antidotes. These data reveal a novel molecular mechanism underlying the cutaneous pathogenesis of lewisite-induced lesions. We also identified novel potential therapeutic targets for lewisite-mediated cutaneous injury.

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions.

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4(+/+) wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4(+/-) heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca(++) homeostasis. ATO induces Ca(++)-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca(++) homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic.

ATF4 regulates arsenic trioxide-mediated NADPH oxidase, ER-mitochondrial crosstalk and apoptosis.

Arsenic is a mitochondrial toxin, and its derivatives, such as arsenic trioxide (ATO), can trigger endoplasmic reticulum (ER) and the associated unfolded protein response (UPR). Here, we show that arsenic induction of the UPR triggers ATF4, which is involved in regulating this ER-mitochondrial crosstalk that is important for the molecular pathogenesis of arsenic toxicity. Employing ATF4+/+ and ATF4-/- MEFs, we show that ATO induces UPR and impairs mitochondrial integrity in ATF4+/+ MEF cells which is largely ablated upon loss of ATF4. Following ATO treatment, ATF4 activates NADPH oxidase by promoting assembly of the enzyme components Rac-1/P47phox/P67phox, which generates ROS/superoxides. Furthermore, ATF4 is required for triggering Ca++/calpain/caspase-12-mediated apoptosis following ATO treatment. The IP3R inhibitor attenuates Ca++/calpain-dependent apoptosis, as well as reduces m-ROS and MMP disruption, suggesting that ER-mitochondria crosstalk involves IP3R-regulated Ca++ signaling. Blockade of m-Ca++ entry by inhibiting m-VDAC reduces ATO-mediated UPR in ATF4+/+ cells. Additionally, ATO treatment leads to p53-regulated mitochondrial apoptosis, where p53 phosphorylation plays a key role. Together, these findings indicate that ATO-mediated apoptosis is regulated by both ER and mitochondria events that are facilitated by ATF4 and the UPR. Thus, we describe novel mechanisms by which ATO orchestrates cytotoxic responses involving interplay of ER and mitochondria.

Hair follicle disruption facilitates pathogenesis to UVB-induced cutaneous inflammation and basal cell carcinoma development in Ptch(+/-) mice.

Hairless mice carrying homozygous mutations in hairless gene manifest rudimentary hair follicles (HFs), epidermal cysts, hairless phenotype, and enhanced susceptibility to squamous cell carcinomas. However, their susceptibility to basal cell carcinomas (BCCs), a neoplasm considered originated from HF-localized stem cells, is unknown. To demonstrate the role of HFs in BCC development, we bred Ptch(+/-)/C57BL6 with SKH-1 hairless mice, followed by brother-sister cross to get F2 homozygous mutant (hairless) or wild-type (haired) mice. UVB-induced inflammation was less pronounced in shaved haired than in hairless mice. In hairless mice, inflammatory infiltrate was found around the rudimentary HFs and epidermal cysts. Expression of epidermal IL1f6, S100a8, vitamin D receptor, repetin, and major histocompatibility complex II, biomarkers depicting susceptibility to cutaneous inflammation, was also higher. In these animals, HF disruption altered susceptibility to UVB-induced BCCs. Tumor onset in hairless mice was 10 weeks earlier than in haired littermates. The incidence of BCCs was significantly higher in hairless than in haired animals; however, the magnitude of sonic hedgehog signaling did not differ significantly. Overall, 100% of hairless mice developed >12 tumors per mouse after 32 weeks of UVB therapy, whereas haired mice developed fewer than three tumors per mouse after 44 weeks of long-term UVB irradiation. Tumors in hairless mice were more aggressive than in haired littermates and manifested decreased E-cadherin and enhanced mesenchymal proteins. These data provide novel evidence that disruption of HFs in Ptch(+/-) mice enhances cutaneous susceptibility to inflammation and BCCs.

Comparative Anatomical Analysis of Bark Structure in 10 Quercus Species.

Detailed anatomical features of bark are used and interpreted in plant taxonomy, phylogenetics, and other areas of plant science. However, the delicate nature of bark cells, combined with the difficulty of obtaining high-quality sections and reliable data, limits the potential for utilizing and processing bark. In this study, the anatomical structure of the bark of 10 Quercus species growing in Yunnan Province, China, was characterized in detail. The results indicate that the anatomical features of the barks of 10 Quercus spp. show a certain degree of consistency. Specifically, sieve tubes are distributed in solitary elements or in small groups, mostly as compound sieve plates containing 2-8 sieve areas, suggesting that Quercus spp. may occupy a conservative evolutionary position. Additionally, for the first time, this study reports the presence of simple sieve plates in the sieve tube elements of Quercus phloem. Each sieve tube element has a companion cell on one side. The companion cell strands contain 2-7 cells. Axial parenchyma is diffuse, with parenchyma strands typically consisting of 4-7 cells; druses are present within chambered crystalliferous cells. Phloem rays are of two distinct sizes and often exhibit dilatation and sclerification, and the ray composition consists of procumbent cells. Sclerenchyma is composed of fibers and sclereids, both of which contain prismatic crystals. Most of the fibers are gelatinous fibers, which are distributed in discontinuous tangential bands of about five cells in width. Sclereids appear in clusters. The presence of sclerenchyma provides mechanical support to the bark, reducing the collapse of the phloem. Periderm usually consists of around 10-30 layers of phellem, and Quercus acutissima and Q. variabilis can reach dozens or hundreds layers. The phelloderm typically consists of from two to five layers, with Q. variabilis having up to ten or more layers. The filling tissue of lenticels in all Quercus species is nonstratified (homogeneous) and largely nonsuberized. Overall, this study enriches our comprehension of Quercus bark anatomy, elucidating evolutionary patterns, functional adaptations, and ecological ramifications within this significant botanical genus.

Race and Gender Differences in Anterior Cruciate Ligament Femoral Footprint Location and Orientation: A 3D-MRI Study.

OBJECTIVE: The femoral tunnel position is crucial to anatomic single-bundle anterior cruciate ligament (ACL) reconstruction, but the ideal femoral footprint position are mostly based on small-sized cadaveric studies and elderly patients with a single ethnic background. This study aimed to identify potential race- or gender-specific differences in the ACL femoral footprint location and ACL orientation, determine the correlation between the ACL orientation and the femoral footprint location. METHODS: Magnetic resonance images (MRIs) of 90 Caucasian participants and 90 matched Chinese subjects were used for reconstruction of three-dimensional (3D) femur and tibial models. ACL footprints were sketched by several experienced orthopedic surgeons on the MRI photographs. The anatomical coordinate system was applied to reflect the ACL footprint location and orientation of scanned samples. The femoral ACL footprint locations were represented by their distance from the origin in the anteroposterior (A/P) and distal-proximal (D/P) directions. The orientation of the ACL was described with the sagittal, coronal and transverse deviation angles. The ACL orientation and femoral footprint position were compared by the two-sided t-test. Multiple regression analysis was used to study the correlation between the orientation and femoral footprint position. RESULTS: The average femur footprint A/P position was -6.6 ± 1.6 mm in the Chinese group and -5.1 ± 2.3 mm in the Caucasian group, (p < 0.001). The average femur footprint D/P position was -2.8 ± 2.4 mm in Chinese and - 3.9 ± 2.0 mm in Caucasians, (p = 0.001). The Chinese group had a mean difference of a 1.5 mm (6.1%) more posterior and 1.1 mm (5.3%) more proximal in the position from the flexion-extension axis (FEA). And the males have a sagittal plane elevation about 4-5° higher than females in both racial groups. Furthermore, for every 1% (0.40 mm) increase in A/P and D/P values, the sagittal angle decreased by about 0.12° and 0.24°, respectively; the coronal angle decreased by about 0.10° and 0.30°, respectively. For every 1% (0.40 mm) increase in D/P value, the transverse angle increased by about 0.14°. CONCLUSION: The significant race- and gender-specific differences in the femoral footprint and orientation of the ACL should be taken in consideration during anatomic single-bundle ACL reconstruction. Furthermore, the quantitative relationship between the ACL orientation and the footprint location might provide some reference for surgeons to develop a surgical strategy in ACL single-bundle reconstruction and revision.

Chlorine induces the unfolded protein response in murine lungs and skin.

Chlorine (Cl2) is an important industrial chemical. Accidental full body exposure to Cl2 poses an environmental, occupational, and public health hazard characterized mainly by injury to the lung, skin, and ocular epithelia. The cellular mechanisms underlying its acute toxicity are incompletely understood. This study examined whether whole body exposure of BALB/c mice to Cl2 in environmental chambers leads to the up-regulation of the unfolded protein response (UPR) in their lungs and skin. Shaved BALB/c mice were exposed to a sublethal concentration of Cl2 (400 ppm for 30 min) and returned to room air for 1 or 6 hours and killed. IL-6 and TNF-α were increased significantly at 1 and 6 hours after Cl2 exposure in the lungs and at 6 hours in the skin. These changes were accompanied by increased UPR signaling (i.e., activation of protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 α, and activating transcription factor 6α) at these time points. The expression of hepcidin, which regulates tissue accumulation and mobilization of iron, was increased in the skin and lungs of Cl2-exposed mice. The data shown herein indicate for the first time the up-regulation of UPR signaling and hepcidin in the skin and lungs of Cl2-exposed mice, which persisted when the mice were returned to room air for 6 hours.

Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein.

Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.

Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption.

Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses.

Loaded open-kinetic-chain exercises stretch the anterior cruciate ligament more than closed-kinetic-chain exercises: In-vivo assessment of anterior cruciate ligament length change.

BACKGROUND: Usage of open-kinetic-chain (OKC) or closed-kinetic-chain (CKC) exercises during rehabilitation planning after anterior cruciate ligament (ACL) reconstruction has been debated for decades. However, the ACL elongation pattern during different rehabilitation exercises at different loadings remains unclear. OBJECTIVES: This study aimed to determine the effects of OKC and CKC exercises on the length of ACL anteromedial bundle (AMB) and posterolateral bundle (PLB) to provide biomechanical support for making rehabilitation schedules. DESIGN: Laboratory Descriptive Study. METHOD: Eighteen healthy volunteers were asked to perform two OKC motions, including non-weight-bearing and 10 kg loaded seated knee extension (OKC-0, OKC-10), as well as two CKC motions, including box squat (BS) and deep single-legged lunge (Lunge). Techniques of 2D-to-3D image registration and 3D ligament simulation were used to quantify length changes of ACL. RESULTS: The motion which led to the least and most ACL elongation were OKC-0 and OKC-10, respectively. The AMB and PLB were significantly longer in OKC-10 than those in OKC-0 during 0-60° and 0-55° of knee flexion (p < 0.01). Compared with reference length, the AMB and PLB were stretched during 0-30° and 0-10° respectively during OKC-10. During CKC exercises, the AMB and PLB were also stretched from 0 to 25°and 0-5°, respectively. Additionally, no significant difference was found in the length change of ACL bundles between BS and lunge. CONCLUSIONS: OKC-0 may be safe for the rehabilitation program after ACL reconstruction, and loaded exercises shall be applied when restricted with >30° in early-stage rehabilitation.

Relationships between position of patellar ridge high point and morphology of resected surface for patellar resurfacing in total knee arthroplasty.

Background: Reproducing the native patellar ridge high point while maximizing osseous coverage is important for the success of patellar replacement, but it cannot always be achieved simultaneously. This study aimed to thoroughly investigate the relationships and their influencing factors between the positions of the high point of patellar ridge (HPPR) and the morphology of the patellar resected surface. Methods: Four hundred seventy-three patients (265 men, 208 women) aged 18 to 50 years with knee injuries before arthroscopy were retrospectively collected for this cross-sectional study. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to construct 3D computer models of the patella and patellar cartilage. The morphometric characteristics of the patellar cut after virtual resection and the HPPR position relative to the patellar cut centre were measured and analyzed. Results: The medial displacements of the HPPR were positively correlated with Wiberg's classification and index (all P<0.001). The mean values of HPPR's medial displacements were 0.15 of the medial width of patellar cut, and 93.2% of all patella ranged from 0 to 0.3. When the implant's apex were placed at 0.15 of the medial width of patellar cut medialized, the proportion of implant placement errors within 1 mm of the native high point was 12% more in female patella (P=0.01), and 7% more in all patella (P=0.03) than 3 mm medialized. Conclusions: Wiberg's system can roughly predicted the medial-lateral position of the HPPR. The HPPR was mainly medially located at the 0.15 of the medial patellar width approximately, and 15% medialized of the implant's apex can better reproduce the native patellar high point than 3 mm medialized. The current results provide basic data for patellar implant selection, preoperative planning, and implant design to reproduce the native patellar high point better while maximizing osseous coverage for patellar resurfacing.

[Digital study on the relationship between position of patellar high point and shape of osteotomy surface in Chinese].

Objective: To measure the position of patellar high point and the shape of the osteotomy surface, and to analyze their relationship, distribution, and gender differences. Methods: A total of 127 patients who needed anterior cruciate ligament reconstruction or meniscus repair due to trauma between September 2020 and September 2021 were selected as the research subjects. There were 71 males and 56 females, with an average age of 30.5 years (range, 19-43 years). There were significant differences in height and body weight between male and female patients ( P<0.05), but no significant difference in age and body mass index ( P>0.05). The three-dimensional model of the patella was reconstructed in Mimics software based on the CT images of the knee joint, and then imported into Geomagic Studio software for virtual osteotomy of the patella. The horizontal axis and vertical axis of the osteotomy surface represented the total width (W) and total height (H) of the osteotomy surface, respectively. Then the osteotomy surface was divided into four quadrants with the two axes: inner proximal, inner distal, outer proximal, and outer distal, and the inner width (W1), proximal height (H1), outer width (W2), and distal height (H2) were measured. The midpoint of the patellar ridge was selected as the patellar high point, and the point projected onto the osteotomy surface was defined as the optimal point for patellar prosthesis positioning (OPPP). The distances of OPPP on the horizontal axis (L1) and vertical axis (L2) relative to the center of the osteotomy surface were measured and L1/W1 and L2/H1 were also calculated; the quadrant distribution of OPPP was recorded. The patients were grouped according to gender, and the morphological parameters of the osteotomy surface (W, W1, W2, H, H1, H2) and the parameters related to the position of the OPPP (L1, L2, L1/W1, L2/H1) were analyzed between groups. Results: The width and height of each osteotomy surface of the patella in males were significantly larger than those in females ( P<0.05). As for the relationship between OPPP and osteotomy surface, the L1 of both male and female patients was 1-7 mm, and there was no significant difference in the distribution between the two groups ( χ 2=8.068, P=0.149); L1/W1 in both male and female patients was mainly 1/10-3/10. The L2 of male patients was 0-5 mm, and that of female patients was -1-4 mm; the difference in distribution between the two groups was significant ( χ 2=15.500, P=0.006); L2/H1 in both male and female patients was mainly 0-1/5. The OPPP of male patients was mainly distributed in the inner proximal (98.59%) and outer proximal (1.41%) quadrants, while the female patients were distributed in the inner proximal (91.07%), inner distal (7.14%), and outer proximal (1.79%) quadrants. There was significant difference in the OPPP quadrant distribution between the two groups ( χ 2=5.186, P=0.036). Conclusion: The OPPP points are widely distributed but mainly concentrated on around 1/5 of the medial patella surface and around 1/10 of the superior patella surface. A small portion of females' OPPP were inferior while all males' OPPP were superior to the center of the patella.

Effect of Time After Injury on Tibiofemoral Joint Kinematics in Anterior Cruciate Ligament-Deficient Knees During Gait.

Background: Anterior cruciate ligament (ACL) injury can lead to changes in tibiofemoral kinematics during gait, but the detailed short-term kinematic changes after ACL injury are still unknown. Purpose: To measure tibiofemoral kinematics during gait in ACL-deficient (ACLD) knees over time after ACL injury. Study Design: Controlled laboratory study. Methods: The authors categorized 76 patients with unilateral ACLD knees into 4 groups based on the time from injury: <3 months (group 1), 3 to 6 months (group 2), >6 to 12 months (group 3), and >12 months (group 4). The controls were 20 participants with ACL-intact knees. Changes in the knee kinematics and range of motion during gait were compared among ACLD groups and those with ACL-intact knees. Results: Compared with controls, the range of motion of flexion in group 1 was significantly lower (6°; P = .033), and the mean knee flexion was significantly increased (0.7°-3.4°) in groups 1 to 4 (all P ≤ .004). There was more internal tibial rotation (2.9°-4.3°) in group 1 and 2, and more anterior tibial translation (4.3 mm) in group 1 during the stance or swing phases than in controls (P ≤ .049 for all). The mean internal tibial rotation and anterior tibial translation significantly decreased from group 1 to group 4 (P < .001 for both). Compared with controls, the mean medial tibial translation was significantly greater (1.2-2.5 mm) in all groups, and more medial tibial translations (2.4-3.7 mm) were observed during the stance phase in groups 1, 3, and 4 (P ≤ .047 for all). Conclusion: ACLD knees displayed a motion impairment walking strategy within 3 months, and a higher-flexion walking strategy increased with time after injury. Excessive anterior translation and internal rotation of the tibia tended to return to normal, while excessive medial translation of the tibia increased in ACLD knees after 6 months postinjury. These results may provide new insight into the compensatory mechanisms and risk factors for premature osteoarthritis in ACLD knees.