Network pharmacology-based investigation of the effects of Shenqi Fuzheng injection on glioma proliferation and migration via the SRC/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the clinic, Shenqi Fuzheng Injection (SFI) is used as an adjuvant for cancer chemotherapy. However, the molecular mechanism is unclear. AIM OF THE STUDY: We screened potential targets of SFI action on gliomas by network pharmacology and performed experiments to validate possible molecular mechanisms against gliomas. MATERIALS AND METHODS: We consulted relevant reports on the SFI and glioma incidence from PubMed and Web of Science and focused on the mechanism through which the SFI inhibits glioma. According to the literature, two primary SFI components-Codonopsis pilosula (Franch.) Nannf. and Astragalus membranaceus (Fisch.) Bunge-have been found. All plant names have been sourced from "The Plant List" (www.theplantlist.org). The cell lines U87, T98G and GL261 were used in this study. The inhibitory effects of SFI on glioma cells U87 and T98G were detected by CCK-8 assay, EdU, plate cloning assay, scratch assay, Transwell assay, immunofluorescence, flow cytometry and Western blot. A subcutaneous tumor model of C57BL/6 mice was constructed using GL261 cells, and the SFI was evaluated by HE staining and immunohistochemistry. The targets of glioma and the SFI were screened using network pharmacology. RESULTS: A total of 110 targets were enriched, and a total of 26 major active components in the SFI were investigated. There were a total of 3,343 targets for gliomas, of which 79 targets were shared between the SFI and glioma tissues. SFI successfully prevented proliferation and caused cellular S-phase blockage in U87 and T98G cells, thus decreasing their growth. Furthermore, SFI suppressed cell migration by downregulating EMT marker expression. According to the results of the in vivo tests, the SFI dramatically decreased the development of tumors in a transplanted tumour model. Network pharmacological studies revealed that the SRC/PI3K/AKT signaling pathway may be the pathway through which SFI exerts its anti-glioma effects. CONCLUSIONS: The findings revealed that the SRC/PI3K/AKT signaling pathway may be involved in the mechanism through which SFI inhibits the proliferation and migration of glioma cells.

Postoperative Antiosteoporotic Treatment with Zoledronic Acid Improves Rotator Cuff Healing but Does Not Improve Outcomes in Female Patients with Postmenopausal Osteoporosis: A Prospective, Single-Blinded, Randomized Study.

PURPOSE: To investigate the effect of the antiosteoporotic agent zoledronic acid (ZA) on rotator cuff healing and clinical outcomes in patients with postmenopausal osteoporosis. METHODS: We prospectively enrolled 138 female patients with postmenopausal osteoporosis who were scheduled to undergo arthroscopic rotator cuff repair (ARCR) from March 2020 to March 2021. Patients were randomly allocated to the ZA group (ARCR followed by intravenous ZA infusions at postoperative Day 1 and 1 year later) and the control group (ARCR alone). All patients were followed up for 24 months. Tendon healing was evaluated by ultrasonography at 6 weeks and 24 months after surgery. The American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Rotator Cuff (WORC) index, and Numeric Rating Scale (NRS) for pain were recorded at each follow-up, and the minimal clinically important difference (MCID) was calculated. RESULTS: A total of 124 patients were included in the final analysis, 61 in the ZA group and 63 in the control group. There was no statistically significant difference in participant characteristics between the 2 groups. The ZA group had a significantly higher tendon healing rate than the control group at 2 years after surgery (odds ratio = 5.0; 95% confidence interval [CI], 1.4-18.7; P = .014). Regarding clinical outcomes, 100% of patients exceeded the MCID in both groups, and no significant differences were found at 2 years after surgery between the 2 groups (ASES: 2.5 [95% CI, -2.2 to 7.2; P = .291]; WORC index: 4.5 [95% CI, -0.117 to 9.117; P = .056]; NRS: -0.1 [95% CI, -0.3 to 0.1; P = .394]). CONCLUSIONS: Antiosteoporotic treatment with ZA reduced the retear rate but did not significantly influence the clinical outcomes after ARCR in female patients with postmenopausal osteoporosis. Outcomes of ARCR showed good results in both groups and exceeded the MCID. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases.

Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

The Necessity of Implant Removal after Fixation of Thoracolumbar Burst Fractures-A Systematic Review.

BACKGROUND: Thoracolumbar burst fractures are a common traumatic vertebral fracture in the spine, and pedicle screw fixation has been widely performed as a safe and effective procedure. However, after the stabilization of the thoracolumbar burst fractures, whether or not to remove the pedicle screw implant remains controversial. This review aimed to assess the benefits and risks of pedicle screw instrument removal after fixation of thoracolumbar burst fractures. METHODS: Data sources, including PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Clinical trials.gov, were comprehensively searched. All types of human studies that reported the benefits and risks of implant removal after thoracolumbar burst fractures, were selected for inclusion. Clinical outcomes after implant removal were collected for further evaluation. RESULTS: A total of 4051 papers were retrieved, of which 35 studies were eligible for inclusion in the review, including four case reports, four case series, and 27 observational studies. The possible risks of pedicle screw removal after fixation of thoracolumbar burst fractures include the progression of the kyphotic deformity and surgical complications (e.g., surgical site infection, neurovascular injury, worsening pain, revision surgery), while the potential benefits of pedicle screw removal mainly include improved segmental range of motion and alleviated pain and disability. Therefore, the potential benefits and possible risks should be weighed to support patient-specific clinical decision-making about the removal of pedicle screws after the successful fusion of thoracolumbar burst fractures. CONCLUSIONS: There was conflicting evidence regarding the benefits and harms of implant removal after successful fixation of thoracolumbar burst fractures, and the current literature does not support the general recommendation for removal of the pedicle screw instruments, which may expose the patients to unnecessary complications and costs. Both surgeons and patients should be aware of the indications and have appropriate expectations of the benefits and risks of implant removal. The decision to remove the implant or not should be made individually and cautiously by the surgeon in consultation with the patient. Further studies are warranted to clarify this issue. LEVEL OF EVIDENCE: level 1.

Lactate Mediates the Bone Anabolic Effect of High-Intensity Interval Training by Inducing Osteoblast Differentiation.

BACKGROUND: High-intensity interval training (HIIT) reportedly improves bone metabolism and increases bone mineral density (BMD). The purpose of the present study was to investigate whether lactate mediates the beneficial effects of exercise on BMD, bone microarchitecture, and biomechanical properties in an established osteoporotic animal model. In addition, we hypothesized that lactate-induced bone augmentation is achieved through enhanced osteoblast differentiation and mineralization. METHODS: A total of 50 female C57BL/6 mice were randomly allocated into 5 groups: the nonovariectomized group, the ovariectomized group (OVX), the HIIT group (OVX + HIIT), the HIIT with lactate transporter inhibition group (OVX + HIIT + INH), and the lactate subcutaneous injection group (OVX + LAC). After 7 weeks of intervention, bone mass, bone strength, and bone formation/resorption processes were evaluated via microcomputed tomography (micro-CT), biomechanical testing, histological analysis, and serum biochemical assays; in vitro studies were performed to explore the bone anabolic effect of lactate at the cellular level. RESULTS: Micro-CT revealed significantly increased BMD in both the OVX + HIIT group (mean difference, 41.03 mg hydroxyapatite [HA]/cm 3 [95% CI, 2.51 to 79.54 mg HA/cm 3 ]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm 3 [95% CI, 4.08 to 76.71 mg HA/cm 3 ]; p = 0.031) compared with the OVX group. Biomechanical testing demonstrated significantly improved mechanical properties in those 2 groups. However, the beneficial effects of exercise on bone microstructure and biomechanics were largely abolished by blocking the lactate transporter. Notably, histological and biochemical results indicated that increased bone formation was responsible for the bone augmentation effects of HIIT and lactate. Cell culture studies showed a marked increase in the expression of osteoblastic markers with lactate treatment, which could be eliminated by blocking the lactate transporter. CONCLUSIONS: Lactate may have mediated the bone anabolic effect of HIIT in osteoporotic mice, which may have resulted from enhanced osteoblast differentiation and mineralization. CLINICAL RELEVANCE: Lactate may mediate the bone anabolic effect of HIIT and serve as a potential inexpensive therapeutic strategy for bone augmentation.

AMPK activator decelerates osteoarthritis development by inhibition of ß-catenin signaling in chondrocytes.

Background: Osteoarthritis (OA) is a common degenerative joint disease with significant negative impact on the quality of life. It has been reported that abnormal upregulation of ß-catenin signaling could lead to OA development; however, the upstream regulatory mechanisms of ß-catenin signaling have not been determined. Methods: Primary rat chondrocytes and ATDC5 chondrocyte cell line were stimulated with AKT2 and treated with or without metformin, an adenosine 5'-monophosphate-activated protein kinase (AMPK) activator. Westerrn blot analysis, luciferase reporter assay and immunofluorescent (IF) staining were performed to examine changes in ß-cateninS552 phosphorylation and ß-catenin nuclear translocation in ATDC5 cells and in primary chondrocytes. Results: We found that metformin inhibited ß-cateninS552 phosphorylation in ATDC5 cells and in primary chondrocytes in a time-dependent manner. Metformin inhibited ß-catenin nuclear translocation and ß-catenin reporter activity. In addition, metformin also attenuated the expression of ß-catenin downstream target genes. We also demonstrated that metformin inhibited ß-cateninS552 phosphorylation in articular cartilage in mice. Conclusion: These findings suggest that metformin may exert its chondro-protective effect at least in part through the inhibition of ß-catenin signaling in chondrocytes. The translational potential of this article: This study demonstrated the interaction between AMPK and ß-catenin signaling in chondrocytes and defined novel molecular targets for the treatment of OA disease.

PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis.

Bone morphogenetic protein 2 (BMP2) effectively induced mesenchymal stem cells (MSCs) osteogenic differentiation hold great potential for bone tissue engineering. However, a global mechanistic view of BMP2-induced osteogenic differentiation of MSCs remains to be fully elucidated. Here, human umbilical cord-derived MSCs (UC-MSCs) were induced with BMP2, three days and five days later, total RNA were extracted and subjected to RNA-sequencing (RNA-Seq) followed with bioinformatic analysis. Osteogenic differentiation abilities were evaluated with Alkaline phosphatase (ALP) staining and osteogenic differentiation marker expression at both mRNA and protein levels. We identified that adenoviral vectors effectively transduced in UC-MSCs and expressed BMP2 in high efficiency. Both on day 3 and day 5, differentially expressed genes (DEGs) were highly enriched in PI3K-Akt signaling pathway. As for the common DEGs among total BMP2 group vs control group, BMP2 (day 3) versus control (day 3) and BMP2 (day 5) versus control (day 5), there were 105 DGEs and highly enriched in PI3K-Akt signaling pathway. Finally, we found that PI3K-Akt signaling inhibitor dramatically inhibited BMP2-iduced osteogenic differentiation of UC-MSCs. We firstly identified that PI3K-Akt signaling pathway plays a pivotal role in BMP2-induced osteogenic differentiation of MSCs, which may apply a new perspective for BMP2 based bone tissue engineering.

The natural product salicin alleviates osteoarthritis progression by binding to IRE1α and inhibiting endoplasmic reticulum stress through the IRE1α-IκBα-p65 signaling pathway.

Despite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.

Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2.

Previous work found that the co-occurring mutations R203K/G204R on the SARS-CoV-2 nucleocapsid (N) protein are increasing in frequency among emerging variants of concern or interest. Through a combination of in silico analyses, this study demonstrates that R203K/G204R are adaptive, while large-scale phylogenetic analyses indicate that R203K/G204R associate with the emergence of the high-transmissibility SARS-CoV-2 lineage B.1.1.7. Competition experiments suggest that the 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly related to ribonucleocapsid (RNP) assembly. Moreover, the 203K/204R virus shows increased infectivity in human lung cells and hamsters. Accordingly, we observe a positive association between increased COVID-19 severity and sample frequency of 203K/204R. Our work suggests that the 203K/204R mutations contribute to the increased transmission and virulence of select SARS-CoV-2 variants. In addition to mutations in the spike protein, mutations in the nucleocapsid protein are important for viral spreading during the pandemic.

Silencing Smad7 potentiates BMP2-induced chondrogenic differentiation and inhibits endochondral ossification in human synovial-derived mesenchymal stromal cells.

BACKGROUND: Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factor for cartilage tissue-engineering, but it also induces robust endochondral ossification. Human synovial-derived mesenchymal stromal cells (hSMSCs) have attracted great interest due to their poor potential for differentiation into osteogenic lineages. Smad7 plays a significant in the endochondral ossification. In this study, we explored a new method to amplify the BMP2-induced chondrogenic differentiation of hSMSCs by downregulating Smad7 and applying a cellular scaffold. METHODS: hSMSCs were isolated from human knee joint synovium from 3 donors through adhesion growth. In vitro and in vivo models of the chondrogenic differentiation of hSMSCs were established. Transgenic expression of BMP2 and silencing of Smad7 and Smad7 was achieved by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining, and RT-PCR analysis of the osteogenic genes RUNX2, Osterix, and Osteocalcin. The chondrogenic differentiation was detected by Alcian blue staining and RT-PCR analysis of the chondrogenic genes SOX9, COL2, and aggrecan. Hypertrophic differentiation was detected by the markers COL10 and MMP13. A subcutaneous stem cell implantation model was established with polyethylene glycol citrate-co-N-isopropylacrylamide (PPCN) scaffolds and athymic nude mice (3/group, 4-6 week-old female) and evaluated by micro-CT, H&E staining, and Alcian blue staining. An immunohistochemistry assay was used to detected COL1 and COL2, and an immunofluorescence assay was used to detect COL10 and MMP13. RESULTS: These hSMSCs identified by flow cytometry. These hSMSCs exhibited lower osteo-differentiation potential than iMads and C3H10T1/2-cells. When Smad7 was silenced in BMP2-induced hSMSCs, the chondrogenic differentiation genes SOX9, COL2, and aggrecan were enhanced in vitro. Additionally, it silencing Smad7 led to a decrease in the hypertrophic differentiation genes COL10 and MMP13. In subcutaneous stem cell implantation assays, immunofluorescence and immunohistochemical staining demonstrated that silencing Smad7 increased the number of COL2-positive cells and decreased the expression of COL1, COL10, and MMP13. CONCLUSION: This study suggests that the application of hSMSCs, cell scaffolds, and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibiting the expression of Smad7 in BMP2-induced hSMSC differentiation may be a new strategy for cartilage tissue-engineering.

BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of mesenchymal stem cells.

Bone morphogenetic protein (BMP) 9 (BMP9) is one of most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Recently, evidence has shown that osteogenesis and angiogenesis are coupled, however, it is unclear whether BMP9 induces MSC differentiation into endothelial-like cells and further promotes blood vessel formation. In the present study, we explored the potential of BMP9-induced angiogenic differentiation of MSCs, and the relationship between BMP9-induced osteogenic and angiogenic differentiation of MSCs. Osteogenic activities and angiogenic differentiation markers were analyzed at mRNA and protein levels. In vivo osteogenic and angiogenic differentiation of MSCs were tested by the ectopic bone formation model. We identified that adenoviral vectors effectively transduced in immortalized mouse embryonic fibroblasts (iMEFs) and expressed BMP9 with high efficiency. We found that BMP9 induces early and late osteogenic differentiation, and it up-regulated osteogenic marker expression in MSCs. Meanwhile, BMP9 induces angiogenic differentiation of MSCs via the expression of vascular endothelial growth factor a (VEGFa) and CD31 at both mRNA and protein levels. CD31-positive cells were also increased with the stimulation of BMP9. The ectopic bone formation tests found that BMP9-induced trabecular bone formation was coupled with the expression of blood vessel formation markers and sinusoid capillary formation. These findings suggest that BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of MSCs.

Are Routine Postoperative Laboratory Tests Necessary After Primary Total Hip Arthroplasty?

BACKGROUND: Recently, the practice of ordering routine postoperative laboratory tests in primary total hip arthroplasty (THA) has been challenged. This study aimed to evaluate the utility of routine postoperative laboratory tests after primary elective THA in an Asian population and identify the risk factors associated with abnormal postoperative laboratory test-related intervention. METHODS: We retrospectively reviewed 395 consecutive patients who underwent primary elective THA at a single tertiary academic center. Patient clinical information and laboratory test results were collected for analysis. RESULTS: A total of 349 (88.4%) patients had abnormal postoperative laboratory test results; most patients had anemia and hypoalbuminemia. Twenty-seven (6.8%) patients received clinical intervention. Of the 307 (77.7%) patients with postoperative anemia, 7 patients received blood transfusion. Factors associated with transfusion were female gender, low body mass index, long operation time, and low preoperative hemoglobin levels. Of the 149 (37.7%) patients with postoperative hypoalbuminemia, 16 received albumin supplementation. Factors associated with albumin supplementation were female gender, long operation time, and low preoperative albumin levels. Although 36 patients had abnormal postoperative creatinine, only 1 patient required specialist consultation. For electrolyte abnormalities, hyponatremia was noted; however, no patient received sodium supplementation. Moreover, 14 patients developed hypokalemia, of which 6 required potassium supplementation; 163 patients had hypocalcemia, of which 2 received calcium supplementation. CONCLUSION: Routine laboratory tests after primary elective THA are unnecessary for most of the patients in modern clinical practice. However, for those with identified risk factors, postoperative laboratory tests still should be performed.

Leonurine Hydrochloride Suppresses Inflammatory Responses and Ameliorates Cartilage Degradation in Osteoarthritis via NF-κB Signaling Pathway.

Leonurine hydrochloride (LH) has been reported to exhibit a number of biological properties such as suppression of inflammation. This study aimed to examine whether the progression of osteoarthritis (OA) could be delayed by the administration of LH in an OA model. Rat chondrocytes were treated with LH under the condition of TNF-α-induced inflammation. After that, real-time PCR and Western blotting were conducted to evaluate relative gene/protein expression levels. For the in vivo study, rats were randomly allocated to a control group (anterior cruciate ligament transection (ACLT) surgery, treatment with saline) and LH group (ACLT surgery, treatment with LH). Articular cartilage degeneration was assessed by histological evaluation. It was found that LH significantly suppressed the expression of MMP-1, MMP-3, MMP-13, IL-6, and ADAMTS-5 in cells via the NF-κB signaling pathway. In addition, it is revealed that intra-articular injection of LH significantly ameliorated cartilage degeneration in a rat OA model. Taken together, these results indicate that LH attenuates progression of OA by inhibition of inflammation via the NF-κB signaling pathway and represents a potential preventive therapy for OA.

The necessity of routine postoperative laboratory tests in enhanced recovery after surgery for primary hip and knee arthroplasty: A retrospective cohort study protocol.

INTRODUCTION: Over the last few decades, the concepts of minimally invasive surgery and enhanced recovery after surgery (ERAS) protocols have been introduced into the field of total joint arthroplasty (TJA), and tranexamic acid (TXA) has been widely used in TJA. Modern-day surgical techniques and perioperative care pathways of TJA have experienced unexpected improvements. Recently, the necessity of the practice of ordering routine postoperative laboratory tests for patients undergoing primary TJA has been challenged, especially in the context of implementation of ERAS protocols in TJA. These studies have consistently suggested that routine postoperative laboratory tests are not necessary in modern-day primary, unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA), and laboratory tests after surgery should only be obtained for patients with risk factors. However, it remains unclear whether routine postoperative laboratory tests after THA and TKA remains justified in the Chinese patient population. Therefore, we developed this study to address this issue. METHODS AND ANALYSIS: This retrospective cohort study will include adult patients who underwent primary unilateral THA or TKA and received multimodal perioperative care pathways according to ERAS protocols. The following patient data will be collected from the electronic medical record system: patients' demographics, preoperative and postoperative laboratory values, operation time, intraoperative blood loss, TXA use, tourniquet use, postoperative length of stay, and any medical intervention directly related to abnormal laboratory values. The main study outcomes are the incidence of acute anemia requiring transfusion and incidence of hypoalbuminemia requiring albumin supplementation. The secondary outcomes are the rates of acute kidney injury, incidence of abnormal serum sodium level, incidence of abnormal serum potassium level, and incidence of abnormal serum calcium level. These clinical data will be analyzed to determine the incidence of abnormal postoperative laboratory values following primary unilateral THA and TKA; to clarify the frequency of any medical intervention directly related to abnormal postoperative laboratory values; and to identify risk factors that predispose patients to have abnormal postoperative laboratory results. STUDY REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1900020690.

Comparison of periprosthetic bone remodeling after implantation of anatomic and tapered cementless femoral stems in total hip arthroplasty: A prospective cohort study protocol.

INTRODUCTION: Current total hip arthroplasty (THA) implant usage trends favor cementless fixation, and plenty studies have demonstrated that numbers of cementless femoral stems are associated with excellent long-term survivorship and functional outcomes. Various types of cementless femoral stems have been developed and utilized in multiple applications, including straight, tapered, anatomic, customized, short, and even neck stems. All of these designs aimed to achieve maximal primary stability and promote osseointegration. Nevertheless, stress-shielding and periprosthetic bone loss continue to occur and remain critical issues in promoting long-term survivorship of THA. Considering anatomic and tapered stems are the most popular cementless designs today, this prospective cohort study aimed to investigate the effect of stem design on stress-shielding and periprosthetic bone remodeling after implantation of an anatomic stem with proximal fixation (Ribbed Hip system; Waldemar Link, Hamburg, Germany) and the direct comparison to a fully coated tapered stem (LCU Hip system; Waldemar Link). MATERIALS AND METHODS: This prospective cohort study will comprise patients who receive primary unilateral THA with the Ribbed anatomic hydroxyapatite (HA)-coated stem or LCU tapered fully HA-coated stem. The changes in periprosthetic bone mineral density after insertion of Ribbed and LCU stem prostheses will be assessed by means of dual-energy X-ray absorptiometry in the periprosthetic region of interest according to Gruen and colleagues. Standard anteroposterior and lateral plain radiography will be performed for qualitative assessment of the periprosthetic bone remodeling. The following items will be analyzed or measured on follow-up radiographs to compare with the initial appearance on the radiographs taken immediately postoperatively: cortical thickness in each Gruen zone, fitness of the distal stem within the isthmus, femoral stem alignment, radiolucent line, reactive line, periosteal bone reactions, and subsidence. Biologic fixation and stability of the cementless implant will be evaluated using Engh grading scale, and heterotopic ossification will be graded according to Brooker classification. Furthermore, Harris hip score and Western Ontario and McMaster Universities Osteoarthritis Index Score will also be assessed for postoperative functional evaluation. These radiologic and clinical assessments will be taken postoperatively, at 6 months, 1, 2, 3, 4, and 5 years after surgery. ETHICS AND DISSEMINATION: This study was approved by The First Affiliated Hospital of Chongqing Medical University Ethics Committee. The study results will be disseminated at national and international conferences and published in peer-reviewed journals. STUDY REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1800017841.