Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

Comprehensive pan-cancer analysis reveals that C5orf34 regulates the proliferation and mortality of lung cancer.

The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive investigations of this gene are lacking. This study aims to elucidate the functional attributes and underlying mechanisms of C5orf34 in cancer. To evaluate its clinical predictive value, we conducted an analysis of the pan-cancerous expression, clinical data, mutation, and methylation data of C5orf34. Additionally, we investigated the correlation between C5orf34 and tumor mutant load (TMB), immune cell infiltration, and microsatellite instability (MSI) through relevant analyses. Furthermore, immunohistochemical (IHC) staining was employed to validate clinical samples, while knockdown and overexpression experiments and transcriptome RNA sequencing were utilized to examine the impact of C5orf34 on LUAD cells. According to our study, C5orf34 exhibits high expression levels in the majority of malignant tumors. The upregulation of C5orf34 is governed by DNA copy number alterations and methylation patterns, and it is closely associated with patients' survival prognosis and immune characteristics, thereby holding significant clinical implications. Furthermore, IHC staining analysis, cellular experiments, and transcriptome RNA sequencing have provided evidence supporting the role of C5orf34 in modulating the cell cycle to promote LUAD proliferation, migration, and invasion. This highlights its potential as a promising therapeutic target. The findings of this investigation suggest that C5orf34 may serve as a valuable biomarker for various tumor types and represent a potential target for immunotherapy, particularly in relation to the proliferation, migration, and apoptosis of LUAD cells.

Global burden of hip fracture: The Global Burden of Disease Study.

This study is the first to measure global burden of hip fracture in patients aged 55 years and older across 204 countries and territories from 1990 to 2019. Our study further proved that the global burden of hip fracture is still large. Hip fractures among males are perhaps underestimated, and older adults should be given more attention. PURPOSE: Hip fracture is a tremendous universal public health challenge, but no updated comprehensive and comparable assessment of hip fracture incidence and burden exists for most of the world in older adults. METHODS: Using data from the Global Burden of Diseases (GBD) 2019, we estimated the number and rates of the incidence, prevalence, and years lived with disability (YLD) of hip fracture across 204 countries and territories in patients aged 55 years and older from 1990 to 2019. RESULTS: In 2019, the incidence, prevalence, and YLDs rates of hip fracture in patients aged 55 years and older were 681.35 (95% UI 508.36-892.27) per 100000 population, 1191.39 (95% UI 1083.80-1301.52) per 100000 population, and 130.78 (95% UI 92.26-175.30) per 100000 population. During the three decades, the incidence among people aged below 60 years showed a downward trend, whereas it showed a rapid upward trend among older adults. All the numbers and rates of hip fractures among females were higher than those among males and increased with age, with the highest number and rate in the highest age group. Notably, the male to female ratio of the incidence for people aged over 55 years increased from 0.577 in 1990 to 0.612 in 2019. Falls were the leading cause among both sexes and in all age groups. CONCLUSIONS: The incidence and the number of hip fractures among patients aged 55 years and older increased over the past three decades, indicating that the global burden of hip fracture is still large. Hip fractures among males are perhaps underestimated, and older adults should be given more attention.

Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

AMPK, a key molecule regulating aging-related myocardial ischemia-reperfusion injury.

Aging leads to the threat of more diseases to the biological anatomical structure and the decline of disease resistance, increasing the incidence and mortality of myocardial ischemia-reperfusion injury (MI/RI). Moreover, MI/RI promotes damage to an aging heart. Notably, 5'-adenosine monophosphate-activated protein kinase (AMPK) regulates cellular energy metabolism, stress response, and protein metabolism, participates in aging-related signaling pathways, and plays an essential role in ischemia-reperfusion (I/R) injury diseases. This study aims to introduce the aging theory, summarize the interaction between aging and MI/RI, and describe the crosstalk of AMPK in aging and MI/RI. We show how AMPK can offer protective effects against age-related stressors, lifestyle factors such as alcohol consumption and smoking, and hypertension. We also review some of the clinical prospects for the development of interventions that harness the effect of AMPK to treat MI/RI and other age-related cardiovascular diseases.

Greater prefrontal activation during sitting toe tapping predicts severer freezing of gait in Parkinson's disease: an fNIRS study.

OBJECTIVE: Previous studies have revealed that, compared with Parkinson's disease (PD) patients without freezing of gait (FoG), the ones with FoG showed greater prefrontal activation while doing lower-limb movements involving standing, walking and turning, which require both locomotor and balance control. However, the relation between FoG and pure locomotor control as well as its underlying mechanism remain unclear. METHODS: A total of 56 PD subjects were recruited and allocated to PD-FoG and PD-noFoG subgroups, and 34 age-matched heathy adults were included as heathy control (HC). Functional near-infrared spectroscopy was used to measure their prefrontal activation in a sitting lower-limb movement task, wherein subjects were asked to sit and tap their right toes as big and as fast as possible. RESULTS: Result of one-way ANOVA (Group: PD-FoG vs. PD-noFoG vs. HC) revealed greater activation in the right prefrontal cortex in the PD-FoG group than in the other 2 groups. Linear mixed-effects model showed consistent result. Furthermore, the right prefrontal activation positively correlated with the severity of FoG symptoms in PD-FoG patients. CONCLUSION: These findings suggested that PD patients with FoG require additional cognitive resources to compensate their damaged automaticity in locomotor control, which is more pronounced in severe FoG patients than milder ones.

Selective Protein of Interest Degradation through the Split-and-Mix Liposome Proteolysis Targeting Chimera Approach.

Proteolysis Targeting Chimera (PROTAC) technology represents a promising new approach for target protein degradation using a cellular ubiquitin-proteasome system. Recently, we developed a split-and-mix nanoplatform based on peptide self-assembly, which could serve as a self-adjustable platform for multifunctional applications. However, the lower drug efficacy limits further biomedical applications of peptide-based SM-PROTAC. In this study, we develop a novel split-and-mix PROTAC system based on liposome self-assembly (LipoSM-PROTAC), concurrent with modification of FA (folate) to enhance its tumor-targeting capabilities. Estrogen receptors (ERα) were chosen as the protein of interest (POI) to validate the efficacy of Lipo degraders. Results demonstrate that this PROTAC can be efficiently and selectively taken up into the cells by FA receptor-positive cells (FR+) and degrade the POI with significantly reduced concentration. Compared to the peptide-based SM-PROTACs, our designed LipoSM-PROTAC system could achieve therapeutic efficacy with a lower concentration and provide opportunities for clinical translational potential. Overall, the LipoSM-based platform shows a higher drug efficacy, which offers promising potential applications for PROTAC and other biomolecule regulations.

Targeting aging with the healthy skeletal system: The endocrine role of bone.

Aging is an inevitable biological process, and longevity may be related to bone health. Maintaining strong bone health can extend one's lifespan, but the exact mechanism is unclear. Bone and extraosseous organs, including the heart and brain, have complex and precise communication mechanisms. In addition to its load bearing capacity, the skeletal system secretes cytokines, which play a role in bone regulation of extraosseous organs. FGF23, OCN, and LCN2 are three representative bone-derived cytokines involved in energy metabolism, endocrine homeostasis and systemic chronic inflammation levels. Today, advanced research methods provide new understandings of bone as a crucial endocrine organ. For example, gene editing technology enables bone-specific conditional gene knockout models, which allows the study of bone-derived cytokines to be more precise. We systematically evaluated the various effects of bone-derived cytokines on extraosseous organs and their possible antiaging mechanism. Targeting aging with the current knowledge of the healthy skeletal system is a potential therapeutic strategy. Therefore, we present a comprehensive review that summarizes the current knowledge and provides insights for futures studies.

Estrogen deficiency induces bone loss through the gut microbiota.

Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in the development of metabolic bone disease. Here, we show that ovariectomized mice had high levels of lipopolysaccharide in serum and gut microbiota dysbiosis through increases in luminal Firmicutes:Bacteroidetes ratio. We depleted the GM through antibiotic treatment and observed improvements in bone mass, bone microstructure, and bone strength in ovariectomized mice. Conversely, transplantation of GM adapted to ovariectomy induced bone loss. However, GM depletion reversed ovariectomy-induced gene expression in the tibia and increased periosteal bone formation. Furthermore, bioinformatics analysis revealed that the G-protein-coupled bile acid receptor (TGR5) and systemic inflammatory factors play key roles in bone metabolism. Silencing TGR5 expression through small interfering RNA (siRNA) in the local tibia and knockout of TGR5 attenuated the effects of GM depletion in ovariectomized mice, confirming these findings. Thus, this study highlights the critical role of the GM in inducing bone loss in ovariectomized mice and suggests that targeting TGR5 within the GM may have therapeutic potential for postmenopausal osteoporosis.

Development of sulfonium tethered peptides conjugated with HDAC inhibitor to improve selective toxicity for cancer cells.

The anti-cancer peptides emerged as new weapons for cancer therapy due to their potent toxicity toward various cancer cells. However, their therapeutic promise is often limited by non-specific toxicity to normal cells. How to improve peptides' selectivity to cancer cells is always a matter to solve. In this manuscript, we designed a sulfonium tethered lytic peptide conjugated with a HDAC inhibitor to improve the selectivity of cancer cells. The sulfonium tethered lytic peptide with improved hydrophilicity and positive charge showed reduced toxicity to both cancer cells and normal cells. When conjugated with the HDAC inhibitor, this peptide showed increased toxicity to cancer cells. Besides, the stabilized peptide HDAC conjugate showed better serum stability than the linear peptide conjugate. For cellular function, the stabilized peptide conjugate could induce cancer cell apoptosis, cell cycle arrest, and influence multiple signal pathways through transcriptome analysis. This design may provide an alternative approach for the development of safe and effective anti-cancer drugs.

Systematic Comprehensive Evaluation of the Mindray CX-9000 Coagulation Analyzer Performance.

BACKGROUND: The aim of the study was to conduct a comprehensive performance evaluation of the Mindray CX-9000 fully automated coagulation analyzer for the detection of the seven coagulation items. METHODS: The performance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), fibrinogen degradation product (FDP), and antithrombin Ⅲ (AT) was validated for precision, linear range, carryover contamination rate, reference interval validation, inter-method agreement, and anti-interference ability. RESULTS: The intra- and inter-precision (coefficient of variation, CV%) of all seven items was less than the target CV%; the carryover contamination rates for different concentrations and between items were < 10%. The slope of the linear regression equation for the theoretical and measured values of the linear range was within 1 ± 0.05 and R ≥ 0.975. The reference interval quoted from the manufacturer's reference interval passed ≥ 95%. The CX-9000 was compared with the results of the reference instrument STAGO R MAX (STA-R MAX) and the p-values for all items ranged from 0.822 to 0.987. Within the concentration range claimed by the manufacturer, the interference errors produced by all items met the manufacturer's claimed criteria, except for triglycerides which produced interference errors > 10% for the FIB, D-D, FDP, and bilirubin which produced interference errors for the FIB and D-D assays. CONCLUSIONS: The CX-9000 automatic coagulation analyzer has good stability and repeatability, a wide linear range of detection, low carryover contamination rate, and high resistance to interference, making it suitable for the testing of clinical specimens.

Banner cloud sign: a novel method for the diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum.

PURPOSE: Dural ossification (DO) is common in patients with ossification of the ligamentum flavum (OLF) and is the leading cause of dural tears. However, the methods used for DO diagnosis are limited. The purpose of this study was to propose a novel CT-based imaging sign, Banner cloud sign (BCs), and clarify its clinical characteristics and correlations with DO. METHODS: 57 OLF patients who underwent thoracic spine decompression surgery in our single-center between January- and October-2018 were recruited and divided into two groups based on the presence of DO. Patient demographics and radiographic data were analyzed. Hematoxylin-eosin staining and micro-CT were used to detect the micro-morphological changes of DO. The diagnostic value of BCs for DO was assessed by sensitivity and specificity. RESULTS: 12 patients with a total of 19 segments were diagnosed as DO. The incidence of DO was 21.1% (12/57) in OLF patients and 9.5% (19/200) in OLF segments. Patients with DO had a shorter disease duration and a higher incidence of cerebrospinal fluid leakage than those without DO. Hematoxylin-eosin staining and micro-CT showed that the dura mater was ossified and fused with ossified ligamentum flavum, and diffusion along the dura mater, like a banner cloud flying on the mountain. The sensitivity and specificity of BCs in DO diagnosis were 78.9 and 90.6%, respectively. CONCLUSION: BCs can vividly and intuitively describe the imaging features of DO and has high diagnostic accuracy. It could be a promising and valuable method for the diagnosis of DO.

Separation of Low-Molecular-Weight Organics by Water-Soluble Macrocyclic Arenes.

In this study, we fabricate a series of water-soluble anionic macrocyclic arenes, including pillar[5]arene (WP5), pillar[6]arene (WP6), leaning pillar[6]arene (WLT6), and biphenyl-extended pillar[6]arene (WBpP6), which show different separation capabilities toward low-molecular-weight organics, such as short chain haloalkanes, cyclic aliphatics, and aromatics, in water. The liquid-liquid distribution experiments are carried out at room temperature. The separation factor for low-molecular-weight organics is evaluated in the extraction of equimolar mixtures. WP6 demonstrates a high extraction efficiency of up to 89% in separating toluene/methylcyclohexane mixtures. These adsorbents also have the advantages of rapid adsorption, high separation efficiency, remarkable selectivity, and good recyclability. This work not only expands the application scope of macrocyclic chemistry, but also has practical research value for organics separation and water purification.

Overturned Loading of Inert CeO2 to Active Co3 O4 for Unusually Improved Catalytic Activity in Fenton-Like Reactions.

In the past decades, numerous efforts have been devoted to improving the catalytic activity of nanocomposites by either exposing more active sites or regulating the interaction between the support and nanoparticles while keeping the structure of the active sites unchanged. Here, we report the fabrication of a Co3 O4 -CeO2 nanocomposite via overturning the loading direction, i.e., loading an inert CeO2 support onto active Co3 O4 nanoparticles. The resultant catalyst exhibits unexpectedly higher activity and stability in peroxymonosulfate-based Fenton-like reactions than its analog prepared by the traditional impregnation method. Abundant oxygen vacancies (Ov with a Co⋅⋅⋅Ov ⋅⋅⋅Ce structure instead of Co⋅⋅⋅Ov ) are generated as new active sites to facilitate the cleavage of the peroxide bond to produce SO4 .- and accelerate the rate-limiting step, i.e., the desorption of SO4 .- , affording improved activity. This strategy is a new direction for boosting the catalytic activity of nanocomposite catalysts in various scenarios, including environmental remediation and energy applications.

Roles of exosomal miRNA in vascular aging.

Aging is a major risk factor for human diseases. As global average life expectancy has lengthened, delaying or reducing aging and age-related diseases has become an urgent issue for improving the quality of life. The vascular aging process represents an important link between aging and age-related diseases. Exosomes are small extracellular vesicles (EV) that can be secreted by almost all eukaryotic cells, and they deliver characteristic biological information about donor cells to regulate the cellular microenvironment, mediate signal transmission between neighboring or distant cells, and affect the expression of target genes in recipient cells. Many recent studies have shown that exosomal microribonucleic acids (miRNA) are involved in the regulation of vascular aging by participating in the physiological functions of vascular cells and the destruction and remodeling of the extracellular matrix (ECM). This review summarizes the regulatory functions of exosomal miRNA in vascular aging because they interact with the ECM, and participate in vascular cell senescence, and the regulation of senescence-related functions such as proliferation, migration, apoptosis, inflammation, and differentiation.

Cellular alterations and crosstalk in the osteochondral joint in osteoarthritis and promising therapeutic strategies.

Osteoarthritis (OA) is a joint disorder involving cartilage degeneration and subchondral bone sclerosis. The bone-cartilage interface is implicated in OA pathogenesis due to its susceptibility to mechanical and biological factors. The crosstalk between cartilage and the underlying subchondral bone is elevated in OA due to multiple factors, such as increased vascularization, porosity, microcracks and fissures. Changes in the osteochondral joint are traceable to alterations in chondrocytes and bone cells (osteoblasts, osteocytes and osteoclasts). The phenotypes of these cells can change with the progression of OA. Aberrant intercellular communications among bone cell-bone cell and bone cell-chondrocyte are of great importance and might be the factors promoting OA development. An appreciation of cellular phenotypic changes in OA and the mechanisms by which these cells communicate would be expected to lead to the development of targeted drugs with fewer side effects.

Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model.

INTRODUCTION: This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats. MATERIALS AND METHODS: Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling. RESULTS: Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E. CONCLUSION: The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. METHODS: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2-infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug's safety profile. RESULTS: Hydroxychloroquine (EC50 = 0.72 µM) was found to be more potent than chloroquine (EC50 = 5.47 µM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. CONCLUSIONS: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

Incidence of and trends in hip fracture among adults in urban China: A nationwide retrospective cohort study.

BACKGROUND: Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. METHODS AND FINDINGS: We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. CONCLUSIONS: Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.