Senescence of Hepatic Stellate Cells by Specific Delivery of Manganese for Limiting Liver Fibrosis.

Senescence of activated hepatic stellate cells (HSCs) is crucial for the regression of liver fibrosis. However, impaired immune clearance can result in the accumulation of senescent HSCs, exacerbating liver fibrosis. The activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is essential for both senescence and the innate immune response. Additionally, the specific delivery to activated HSCs is hindered by their inaccessible anatomical location, capillarization of liver sinusoidal endothelial cells (LSECs), and loss of substance exchange. Herein, we propose an antifibrotic strategy that combines prosenescence with enhanced immune clearance through targeted delivery of manganese (a cGAS-STING stimulator) via albumin-mediated transcytosis, specifically aimed at inducing senescence and eliminating activated HSCs in liver fibrosis. Our findings demonstrate that only albumin efficiently transfers manganese to activated HSCs from LSECs via transcytosis compared to liposomes, resulting in significant antifibrotic effects in vivo while exhibiting negligible toxicity.

Improved Photodynamic Therapy Based on Glutaminase Blockage via Tumor Membrane Coated CB-839/IR-780 Nanoparticles.

Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.

Phase-Change Based Oxygen Carriers Improve Acute Cerebral Hypoxia.

Stroke is the second leading cause of death worldwide, and hypoxia is a major crisis of the brain after stroke. Therefore, providing oxygen to the brain microenvironment can effectively protect neurons from damage caused by cerebral hypoxia. However, there is a lack of timely and effective means of oxygen delivery clinically to the brain for acute cerebral hypoxia. Here, a phase-change based nano oxygen carrier is reported, which can undergo a phase change in response to increasing temperature in the brain, leading to oxygen release. The nano oxygen carrier demonstrate intracerebral oxygen delivery capacity and is able to release oxygen in the hypoxic and inflammatory region of the brain. In the acute ischemic stroke mouse model, the nano oxygen carrier can effectively reduce the area of cerebral infarction and decrease the level of inflammation triggered by cerebral hypoxia. By taking advantage of the increase in temperature during cerebral hypoxia, phase-change oxygen carrier proposes a new intracerebral oxygen delivery strategy for reducing acute cerebral hypoxia.

Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-ß Axis in Dendritic Cells.

The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1α expression, a transcription factor that amplifies TGF-ß production and inhibits the effective T cell function. In vivo, knock-out of HIF-1α in DCs or using a HIF-1α inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1α protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1α-TGF-ß axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration.

Phase and detuning control of the unidirectional reflection amplification based on the broken spatial symmetry.

In order to achieve the tunable unidirectional reflection amplification in a uniform atomic medium that is of vital importance to design high-quality nonreciprocal photonic devices, we propose a coherent closed three-level Δ-type atomic system by applying a microwave field, and a strong coupling field of linear variation along the x direction to control a probe field. In our scheme, the linearly increased coupling field destroys the spatial symmetry of probe susceptibility and effectively suppresses the reflection of one side; the microwave field constructs closed loop transitions to amplify the probe field and causes phase changes. The numerical simulation indicates that the unidirectional reflection amplification is sensitive to the relative phase ϕ and the coupling detuning Δc. Our results will open a new route toward harnessing optical non-reciprocity, which can provide more convenience and possibilities in the experimental realization.

A comprehensive meta-analysis of risk factors associated with osteosarcopenic obesity: a closer look at gender, lifestyle and comorbidities.

This study reviewed the risk factors of Osteosarcopenic obesity (OSO), a condition linking weak bones, muscle loss, and obesity. Notable associations were found with female gender, physical inactivity, hypertension, and frailty. Recognizing these early can aid targeted prevention, emphasizing further research for improved understanding and strategies. PURPOSE: Osteosarcopenic obesity (OSO) represents a confluence of osteopenia/osteoporosis, sarcopenia, and obesity, contributing to increased morbidity and mortality risks. Despite escalating prevalence, its risk factors remain under-explored, necessitating this comprehensive systematic review and meta-analysis. METHODS: A diligent search of PubMed, Scopus, and Cochrane databases was conducted for pertinent studies until June 2023. The random-effects model was employed to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs), scrutinizing various risk factors like age, gender, lifestyle factors, and common comorbidities. RESULTS: Our meta-analysis incorporated 21 studies comprising 178,546 participants. We identified significant associations between OSO and factors such as female gender (OR 1.756, 95% CI 1.081 to 2.858), physical inactivity (OR 1.562, 95% CI 1.127-2.165), and hypertension (OR 1.482, 95% CI 1.207-1.821). Conversely, smoking (OR 0.854, 95% CI 0.672-1.084), alcohol consumption (OR 0.703, 95% CI 0.372-1.328), and dyslipidemia (OR 1.345, 95% CI 0.982-1.841) showed no significant associations. Remarkable heterogeneity was observed across studies, indicating considerable variation in effect sizes. Notably, OSO was strongly associated with frailty (OR 6.091; 95% CI 3.576-10.375). CONCLUSIONS: Our study underscored the substantial role of female gender, physical inactivity, and hypertension in the development of OSO, whilst suggesting a strong link between OSO and frailty. These findings emphasize the importance of early risk factor identification and targeted interventions in these groups. Further research is warranted to decode the complex pathophysiological interplay and devise effective prevention and management strategies.

Targeted Delivery of Catalase and Photosensitizer Ce6 by a Tumor-Specific Aptamer Is Effective against Bladder Cancer In Vivo.

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

Metallic Re3O2 with mixed-valence states.

Rhenium (Re) shows the richest valence states from +2 to +7 in compounds, but its mixed-valence states are still missing thus far. In this work, we have explored the Re-O phase diagram with a wide range of stoichiometric compositions under high pressure through first-principles structural search calculations. Besides identifying two novel high-pressure phases of ReO2 and ReO3, we reveal two hitherto unknown Re-rich Re3O2 and O-rich ReO4 compounds. Re atoms in Re3O2 show mixed-valence states due to their inequivalent coordination environments, the first example in Re-based compounds. Electronic structure calculations demonstrate that the four discovered Re-O phases exhibit metallicity contributed by Re 5d electrons. Among them, ReO3 has a predicted critical temperature of up to 12 K at 50 GPa, derived from the interaction between Re 5d electrons and Re-derived low-frequency phonons. Our study points to new opportunities to disclose novel transition metal compounds with mixed-valence states.

MnO2 and roflumilast-loaded probiotic membrane vesicles mitigate experimental colitis by synergistically augmenting cAMP in macrophage.

BACKGROUND: Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC. RESULTS: Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia. CONCLUSIONS: A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.

Disability level's impact on blood pressure-mortality association in older long-term care adults: evidence from a large Chinese cohort study.

BACKGROUND: Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. METHODS: This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. RESULTS: The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10-1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16-1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18-1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11-1.20) in severe disability group both demonstrated an increased all-cause mortality risk. CONCLUSION: The optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2100049973).

Ensemble-Based Virtual Screening Led to the Discovery of Novel Lead Molecules as Potential NMBAs.

Neuromuscular blocking agents (NMBAs) are routinely used during anesthesia to relax skeletal muscle. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels; NMBAs can induce muscle paralysis by preventing the neurotransmitter acetylcholine (ACh) from binding to nAChRs situated on the postsynaptic membranes. Despite widespread efforts, it is still a great challenge to find new NMBAs since the introduction of cisatracurium in 1995. In this work, an effective ensemble-based virtual screening method, including molecular property filters, 3D pharmacophore model, and molecular docking, was applied to discover potential NMBAs from the ZINC15 database. The results showed that screened hit compounds had better docking scores than the reference compound d-tubocurarine. In order to further investigate the binding modes between the hit compounds and nAChRs at simulated physiological conditions, the molecular dynamics simulation was performed. Deep analysis of the simulation results revealed that ZINC257459695 can stably bind to nAChRs' active sites and interact with the key residue Asp165. The binding free energies were also calculated for the obtained hits using the MM/GBSA method. In silico ADMET calculations were performed to assess the pharmacokinetic properties of hit compounds in the human body. Overall, the identified ZINC257459695 may be a promising lead compound for developing new NMBAs as an adjunct to general anesthesia, necessitating further investigations.

Metagenomic analysis reveals distinct changes in the gut microbiome of obese Chinese children.

BACKGROUND: The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. RESULTS: We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. CONCLUSIONS: Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.

Tailored diffractions of asymmetric columns and symmetric rows in two-dimensional multi-element phase gratings.

Two-dimensional multi-element phase gratings can be engineered to show an even symmetry along one direction while an odd symmetry along the other direction in terms of offset refractive indices in each unit cell. The interplay of such even and odd symmetries has been explored to tailor diffraction columns and rows on demand by making offset refractive indices to satisfy specific requirements and hence attain different types of destructive interference. The resultant tailoring effects include the directional column elimination, the grouped column elimination, and the directional column selection as well as the natural row absence, the grouped row elimination, and the central row selection.

Investigation of dynamic wind speed impacts on radiative transmittance and reflectance in the ocean-sea fog system.

Frequent fog and dynamic wind speeds in the ocean significantly impact the radiation transmittance and reflectance on the sea surface, substantially challenging remote sensing and target detection in marine environments. Establishing a model to study the radiative transfer more accurately in ocean-sea fog systems under dynamic wind speed conditions is crucial. Here, a multichannel Monte Carlo (Mc-MC) model is introduced to investigate radiative transfer in ocean-fog systems, which is more realistic and has greater potential than the traditional MC (Tra-MC) approach. Addressing the challenges of dynamic wind speed, this paper introduces two specialized dynamic wind speed models. One prioritized the accurate simulation of changing sea surface wind speeds, and we investigated the transmittance and reflectance of six regions in the Pacific and Atlantic Oceans under this model. The other is proposed for investigating the effect of dynamic wind speed on radiative transfer. The experimental results indicate that an increase in the wind speed dynamic factor accelerates the rate of wind speed changes, thereby intensifying the instability of the radiative transfer transmittance and reflectance. In addition, the light around both the 1 µm and 2 µm wavelengths exhibit high transmittance, but the light surrounding 1 µm has relatively weaker stability compared to that surrounding 2 µm. These investigations provide valuable insights for infrared remote sensing, target detection, and the development of light sources suitable for marine applications.

Manipulation of single stored-photon with microwave field based on Rydberg polariton.

We demonstrate a coherent microwave manipulation of a single optical photon based on a single Rydberg excitation in an atomic ensemble. Due to the strong nonlinearities in a Rydberg blockade region, a single photon can be stored in the formation of Rydberg polariton using electromagnetically induced transparency (EIT). The manipulation of the stored single photon is performed by applying a microwave field that resonantly couples the nS1/2 and nP3/2, while the coherent readout is performed by mapping the excitation into a single photon. We achieve a single photon source with g(2)(0) = 0.29 ± 0.08 at 80S1/2 without applying microwave fields. By implementing the microwave field during the storage time and retrieval process, we show the Rabi oscillation and modulation of stored photons that can be controlled to retrieve early or late. Rapid modulation frequencies up to 50 MHz can be obtained. Our experimental observations can be well explained via numerical simulations based on an improved superatom model accounting for the dipole-dipole interactions in a Rydberg EIT medium. Our work provides a way to manipulate the stored photons by employing the microwave field, which is significant for developing quantum technologies.

Biphoton generation enhanced by nonlocal nonlinearity via Rydberg interactions.

Strongly correlated Stokes and anti-Stokes photon pairs (biphotons) exhibiting very large generation rates and spectral brightnesses could be attained at extremely low pump powers and optical depths. This is realized via spontaneous four-wave mixing in cold atoms with enhanced nonlocal (Rydberg) optical nonlinearities and prepared into a dark state with a large population imbalance. The scheme works with all light fields on resonance yet with negligible linear absorption and Raman gain.

Research Progress in Oxygen Carrier Design and Application.

Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.

Gut microbiota trajectory in ß-thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The gut microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) changes, leading to complications such as acute graft-versus-host disease (GVHD). This study aimed to evaluate the human microbiota composition before and after HSCT in ß-thalassemia major (ß-TM) children. METHOD: Twenty-two ß-TM children who received allo-HSCT between December 2018 and March 2020 were enrolled. They were followed up for more than 100 days after HSCT, and their gut microbiota information and disease data were recorded at five-time points. RESULTS: The dominant bacteria were Bacteroidetes and Firmicutes at the phylum level and Lachnospiraceae at the family level before and after HSCT. In the differential analysis, Ruminococcaceae constantly decreased after HSCT. Besides, Rothia mucilaginosa was the most abundant 2 months after HSCT compared to before it. Additionally, GVHD patients presented decreased levels of Bacteroidetes compared to those without GVHD. Moreover, Blautia levels significantly decreased in critically ill GVHD patients. CONCLUSION: The gut microbiota of the 22 ß-TM children showed a clear trend of destruction and reconstruction within 100 days after HSCT. The extra-oral infections and inflammations of Rothia mucilaginosa, a Gram-positive bacterium of the normal oropharyngeal tract microbiota, might play an important role in the recovery process of HSCT. Finally, decreased Bacteroidetes levels were associated with GVHD onset.

Emergent superconductivity in TaO3 at high pressures.

Tantalum (Ta) is an interesting transition metal that exhibits superconductivity in its elemental states. Additionally, several Ta chalcogenides (S and Se) have also demonstrated superconducting properties. In this work, we propose the existence of five high-pressure metallic Ta-O compounds (e.g., TaO3, TaO2, TaO, Ta2O, and Ta3O), composed of polyhedra centered on Ta/O atoms. These compounds exhibit distinct characteristics compared to the well-known semiconducting Ta2O5. One particularly interesting finding is that TaO3 shows an estimated superconducting transition temperature (Tc) of 3.87 K at 200 GPa. This superconductivity is primarily driven by the coupling between the low-frequency phonons derived from Ta and the O 2p and Ta 5d electrons. Remarkably, its dynamically stabilized pressure can be as low as 50 GPa, resulting in an enhanced electron-phonon coupling and a higher Tc of up to 9.02 K. When compared to the superconductivity of isomorphic TaX3 (X = O, S, and Se) compounds, the highest Tc in TaO3 is associated with the highest NEF and phonon vibrational frequency. These characteristics arise from the strong electronegativity and small atomic mass of the O atom. Consequently, our findings offer valuable insights into the intrinsic physical mechanisms of high-pressure behaviors in Ta-O compounds.

Effect of China's long-term care insurance on health outcomes of older disabled people: role of institutional care.

Since the public long-term care insurance (LTCI) system was piloted in Chengdu, China, in October 2017, there has been considerable growth of LTC institutions in China. This study aimed to evaluate the health value effect of LTCI in older patients with severe disabilities in an LTC institution. This prospective study was based on data from 985 severe disability patients with or without LTCI from October 2017 to May 2021 in the Eighth People's Hospital, Chengdu, China. The Cox proportional hazard model estimated LTCI's health value, including survival probability and risk of pneumonia/pressure ulcers. Subgroup analysis was performed for sex, age, Charlson Comorbidity Index (CCI), and the number of drugs. In the analysis, 519 and 466 patients in LTCI and non-LTCI groups were included, respectively. In adjusted Cox analyses, the LTCI group had a significantly elevated survival rate compared with the non-LTCI groups at 12 months (P < .001, hazard ratio (HR) = 1.758, 95% confidence interval (CI) 1.300-2.376). At 40 months, the adjusted survival rate was 62.6% in the LTCI group, which was significantly higher (53.7%; P = .003, HR = 1.438, 95% CI 1.131-1.831). The subgroups of patients aged 60 to 79 years (interaction P = .007) and with CCI ≥ 3 (interaction P = .026) were more significantly associated with survival improvement than those aged >80 years and with CCI< 3. The LTCI group was also at lower risk for hospital-acquired pneumonia (P = .016, HR 0.622, 95% CI 0.422-0.917) and pressure ulcers (P = .008, HR 0.695, 95% CI 0.376-0.862). The improved survival of LTCI remained stable in sensitivity analyses. For older patients with severe disabilities, in a LTC institution, LTCI significantly improved their health profile and longevity after a year, suggesting the large role and development potentiality of institution care in the LTCI system of China.