The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999-2018.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age. METHODS: A total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were selected and divided into the younger group (< 65 yrs) and the older group (≥ 65 yrs). Baseline TyG was calculated and cause-specific mortality status [cardiovascular (CV), cancer, and non-CV] was determined by the NHANES Public-Use Linked Mortality Files through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were used to evaluate the association between TyG and all-cause/cause-specific mortality. Interaction between TyG and age to mortality was also evaluated. Sensitivity analyses were performed in patients without cardiovascular disease, chronic kidney disease, or insulin treatment. RESULTS: During a median follow-up of 107 months, 805 all-cause deaths occurred, of which 250 and 144 were attributed to CV and cancer deaths. There was a significant age interaction to the association between TyG and all-cause/non-CV mortality. After fully adjusting for potential confounding factors, higher TyG was associated with an increased risk of all-cause [TyG per unit increase Hazard Ratio (HR) 1.33, 95% Confidence Interval (CI) 1.06-1.66, p = 0.014] and non-CV mortality (TyG per unit increase HR 1.54, 95% CI 1.18-2.01, p = 0.002) only in the younger group, but not in the older group. There was no significant association between TyG and CV/cancer death in the total cohort and two age subgroups. Similar results were found in RCS and sensitivity analyses. CONCLUSION: In a national sample of patients with T2DM in the United States, we found that the association between TyG and all-cause/non-CV death was modified by age. Higher TyG was only associated with an increased risk of all-cause/non-CV only in T2DM patients younger than 65 years old, but not in older patients.

On the error performance and channel capacity of a uniquely decodable coded FSO system over Malaga turbulence with pointing errors.

Our previous work has proved that the uniquely decodable code (UDC) has the ability of enhancing the throughput of a free space optical communication (FSO) system. This paper quantitatively analyzes the error performance and channel capacity of the UDC-FSO system under Malaga turbulence and pointing errors. We first propose the minimum distance of the superimposed patterns (MDSP) approximation to reveal the universal symbol error rate (SER) for UDC-FSO systems. A closed form expression of SER is further deduced for a special case of 2 TXs. Based on the deduced SER, the upper and lower bounds of bit error rate (BER) can be obtained. Additionally, the discrete channel capacity of the UDC-FSO system is defined and deduced according to different superposition patterns, as well as the channel capacity gain. Both simulation and experiment verify the accuracy of the MDSP and SER's expressions. It's also discovered that the channel capacity of the UDC-FSO system is superior to the conventional end-to-end (E2E) link, where maximal channel capacity is limited by the UDC codebooks.

Likelihood based synchronization algorithms in optical pulse position modulation systems with photon-counting receivers.

Deep space optical communication (DSOC) is becoming a hot topic. Pulse position modulation (PPM) is an effective tool to realize DSOC benefiting from the feature of high sensitivity. In this paper, we analyze 2 × 1 optical PPM systems with photon-counting detectors, where the distance difference between the two links causes asynchronous superpositions at the receiving end. Two synchronization algorithms are proposed to estimate the time offsets of the two links, which are the optimal Global Maximum Likelihood Estimation (GMLE) and the suboptimal Integer Comparison - Fractional Likelihood Estimation (ICFLE). The complexities of the two methods are also compared. In order to measure the two proposed algorithms, the Cramer-Rao bounds (CRB) are derived. According to simulation results, both the two proposed algorithms approach the deduced CRBs. Furthermore, an equivalent experiment is designed to verify the feasibility and effectiveness of the proposed algorithms. It's also indicated that the proposed algorithms may be utilized in practical systems.

Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes-induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis.

BACKGROUND INFORMATION: Diabetes-induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism. A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC-1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC-1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy. RESULTS: CLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose-treated GC-1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl-2 expression, elevated Bax expression and cleavage of Caspase-3/-9 in GC-1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin-1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC-1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU-overexpressing GC-1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment. CONCLUSIONS: CLU expression is suppressed during diabetes-induced testicular damage, whereas CLU overexpression alleviates diabetes-induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.

Antibiotic resistance of Helicobacter pylori isolated from children in Chongqing, China.

The resistance of Helicobacter pylori (H. pylori) to antibiotics has been increasing worldwide and varies across different geographic areas and times. Limited studies reported the prevalence of antibiotic resistance and its related gene mutations in children in Chongqing, a city located in southwest China. We collected 112 H. pylori strains isolated from gastric biopsies of 156 children at Children's Hospital of Chongqing Medical University and calculated resistance rates of these strains to six antibiotics. The A2143G and A2142G mutations in 23S rRNA gene, which are related to clarithromycin resistance, and Asn87 and Asp91 mutations in gyrA gene, which are related to levofloxacin resistance, were investigated in 102 strains. The resistance rates to clarithromycin, metronidazole, and levofloxacin were 47.3% (53/112), 88.4% (99/112), and 18.8% (21/112), respectively. No resistance to amoxicillin, tetracycline, and furazolidone was observed. Dual and triple resistance percentages were 37.5% (42/112) and 10.7% (12/112), respectively. The detection rate of A2143G mutation in 23S rRNA gene was 83.3% (40/48). The detection rates of mutations of Asn87 and Asp91 in gyrA gene were 52.6% (10/19) and 36.8% (7/19), respectively. Conclusion: The prevalence of H. pylori resistance to clarithromycin, metronidazole, and levofloxacin was high in children in Chongqing, China. The A2143G mutation was detected in most clarithromycin-resistant strains, and Asn87 and Asp91 of gyrA mutation points were common in levofloxacin-resistant strains. In clinical practice, anti-H. pylori therapy should be individualized based on a susceptibility test.  What is Known: • The resistance of H. pylori to antibiotics changes with the geographic areas and that in Asia the resistance rate is high. • Mutation plays a vital role in antibiotics resistance of H. pylori. What is New: • High resistance rates to single and multiple antibiotics in children of Chongqing, a city located in southwest China, were observed. • Molecular assays showed good conformance with susceptibility test results to direct antibiotic resistance of H. pylori.

[Impact of 4-bromobiphenyl ether on the expression of γH2AX in the rat testis].

Objective: To investigate the effects of monobromobiphenyl ether (4-BDE) on the expression of γH2AX in the rat testis, and the possible mechanism of 4-BDE affecting the reproductive function of the male rats. METHODS: Twenty-four SD male rats were randomly divided into 4 groups: control and low-, medium- and high-dose 4-BDE, the control rats treated intragastrically with olive oil, and the animals in the latter three groups with 4-BDE at 50, 100 and 200 mg/kg/d, respectively, all for 30 consecutive days. Then all the rats were killed and the testis tissues harvested for HE staining, examination of the apoptosis of the cells by TUNEL and determination of the expressions of H2AX mRNA and γH2AX by q-PCR and Western blot. RESULTS: HE staining manifested occasional reduction or absence of spermatogonial and Sertoli cells in the seminiferous tubules in the medium- and high-dose 4-BDE groups. Compared with the controls, the rats exposed to 4-BDE showed a significant dose-dependent increase in the apoptosis of the testis tissue (P < 0.05), even more significant in the medium- and high-dose 4-BDE groups than in the low-dose group (P < 0.05). There was a dose-effect relationship in the apoptosis index, but with no statistically significant difference between the medium- and high-dose 4-BDE groups (P > 0.05). The results of q-PCR exhibited no statistically significant difference in the expression level of H2AX mRNA either between the control and 4-BDE-exposed rats (P > 0.05) or among the three 4-BDE groups (P > 0.05). The expression of the γH2AX protein was remarkably higher in the 4-BDE groups than in the control (P < 0.05), but not significantly different among the 4-BDE groups (P > 0.05). CONCLUSIONS: Exposure to 4-BDE at 100 or 200 mg/kg/d damages the structure of seminiferous tubules, increases the apoptosis of testicular cells, significantly up-regulates the expression of the γH2AX protein, and consequently increases DNA double-strand breaks (DSB) in the rat testis. The apoptosis of testicular cells may be related to DSB./.

The Issue of Recurrently Positive Patients Who Recovered From COVID-19 According to the Current Discharge Criteria: Investigation of Patients from Multiple Medical Institutions in Wuhan, China.

The current discharge criteria for COVID-19 require that patients have 2 consecutive negative results for reverse transcription polymerase chain reaction (RT-PCR) detection. Here, we observed that recurrent positive RT-PCR test results in patients with 3 consecutive negative results (5.4%) were significantly decreased compared with those in patients with 2 consecutive negative results (20.6%); such patients reported positive RT-PCR test results within 1 to 12 days after meeting the discharge criteria. These results confirmed that many recovered patients could show a positive RT-PCR test result, and most of these patients could be identified by an additional RT-PCR test prior to discharge.

[Protective effect of taurine against formaldehyde-induced male reproductive toxicity in adult male rats].

OBJECTIVE: To study the effect of taurine on the reproductive toxicity damage induced by formaldehyde (FM) in adult male rats. METHODS: Forty-eight SD adult male rats were equally randomized into a normal control, an FM poisoning (FMP), a taurine intervention (TI), and an TI+FMP group. The control rats were given normal diet and gavage of saline, the rats of the FMP group treated intraperitoneally with FM at 10 mg/kg qd alt, those of the TI group intragastrically with taurine at 100 mg/kg qd, and those of the TI+FMP group with both FM and taurine at the above doses. After 30 days of treatment, the blood of the abdominal cardinal vein of the rats was extracted for measurement of the levels of serum hormones, the body weight, testis weight and testicular coefficient obtained, the testis tissue subjected to HE staining, and the expressions of Bcl-2 and Bax determined by Western blot. RESULTS: There were no statistically significant differences among the four groups of rats in the body weight, testis weight or testicular coefficient (P > 0.05). The rats in the FMP group showed obviously decreased testicular spermatogenic cells and disordered layers and loose structure of seminiferous tubules, which were basically restored to normal after taurine intervention. Compared with the normal controls, the animals of the TI group exhibited no significant abnormality, but those of the FMP group presented markedly reduced levels of serum T, LH and FSH (P < 0.05), and dramatically increased level of Gonadotropin-releasing hormone (GnRH) (P < 0.01). The levels of serum hormones were all significantly improved (P < 0.05) and that of the apoptotic protein Bax basically returned to normal (P < 0.05) after taurine intervention. CONCLUSIONS: Taurine has a certain protective effect against male reproductive toxicity caused by formaldehyde.

[Ultrasonographic and clinical features of common testicular germ cell tumors in children].

OBJECTIVE: To study the ultrasonographic manifestations and clinical features of common pediatric testicular germ cell tumors (TGCT) in children. METHODS: We retrospectively analyzed the laboratory, ultrasonographic and clinical data on 92 children with TGCT diagnosed in Shanghai Children's Hospital from March 2013 to January 2019, and investigated the values of the serum alpha-fetoprotein (AFP) level and maximum diameter of tumors in the diagnosis of benign and malignant tumors using the ROC curve. RESULTS: Of the 92 cases of pediatric TGCT, 64 (69.6%) were pathologically confirmed as benign tumors, including 40 cases of teratoma (62.5%), 18 cases of epidermoid cyst (28.1%) and 6 cases of dermoid cyst (9.4%), and the other 28 (30.4%) as malignant neoplasms, including 26 cases of yolk sac tumor (YST, 92.9%) and 2 cases of mixed germ cell tumor (MGCT, 7.1%). Ultrasonography showed that 62.5% of the teratomas were cystic-solid mixed (25/40) and 32.5% solid masses (12/40), that 33.3% of the epidermoid cysts exhibited a typical sign of "onion ring" (6/18) and 22.2% that of capsular calcification (4/18), and that 42.3% of the YSTs displayed isoechoic (11/26), 30.9% hypoechoic (8/26) solid masses without calcium and 26.9% cystic anechoic lesions (7/26). Color Doppler blood flow imaging manifested abundant blood flow signals in most of the YSTs (25/26, 96.2%) but none in either the epidermoid or the dermoid cysts. The area under the ROC curve (AUC) of the serum AFP value was 0.985, with an optimal cutoff value of 124.2 ng/ml, and the sensitivity and specificity of AFP in the diagnosis of benign and malignant tumors were 92.9% and 93.7%, respectively. The AUC of the maximum diameter of the tumors was 0.796, with an optimal cutoff value of 2.7 cm, and the sensitivity and specificity of the maximum diameter of the tumors in the diagnosis of benign and malignant neoplasms were 57.1% and 93.7%, respectively. CONCLUSIONS: Ultrasonographic images have different characteristic manifestations for different pathological types of pediatric TGCT. Pediatric TGCT has a good prognosis and radical orchiectomy should be considered for the treatment of the tumors with serum AFP ≥ 124.2 ng/ml and a diameter ≥ 2.7 cm.

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis.

BACKGROUND: Although increased accumulation of neutrophils has been noted in chronic rhinosinusitis (CRS), the function and regulation of neutrophils in CRS are largely unknown. IL-36 family cytokines may play an important role in neutrophilic inflammation. OBJECTIVE: This study sought to investigate the expression and function of IL-36 cytokines in CRS. METHODS: Quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to investigate the expression of IL-36 cytokines and IL-36 receptor (IL-36R) in sinonasal mucosa. The expression of IL-36R on neutrophils in polyps and blood was measured by flow cytometry. Purified blood neutrophils were cultured to investigate the regulation of IL-36R expression. The cleavage of IL-36γ was detected by Western blotting. Dispersed nasal polyp cells were treated with IL-36γ with or without elastase inhibitor and dexamethasone. RESULTS: Neutrophil infiltration and expression of IL-36 cytokines and IL-36R were upregulated in both CRS with and without nasal polyps. IL-36γ was the most abundant isoform and mainly expressed by epithelial cells in CRS. Neutrophils were the principal IL-36R+ cell type in polyps. IL-36R expression was almost absent in blood neutrophils and upregulated by IL-6, IL-1ß, and Dermatophagoides pteronyssinus group 1. Elastase activity was increased in polyps and degraded full-length IL-36γ. Consistently, the levels of cleaved IL-36γ were increased in polyps. Full-length IL-36γ promoted the production of matrix metalloproteinase 9; IL-17A; and chemokine (C-X-C motif) ligands 1, 2, and 8 from dispersed nasal polyp cells, which was abolished by elastase inhibitor. The proinflammatory effect of IL-36γ was not suppressed by dexamethasone. CONCLUSIONS: Increased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.

[Reproductive toxicity of PBDE in males: Advances in studies].

Polybrominated biphenyl ether (PBDE) is a kind of brominated aromatic hydrocarbon commonly used as a flame retardant and now considered as one of the persistent organic pollutants, which generally exists in the environment and organisms. Studies have shown that PBDEs have an endocrine disrupting effect, neurotoxicity, developmental toxicity, reproductive toxicity, and the ability of inducing reproductive toxicity in men by reducing semen quality, affecting testis germ cells and interfering with reproductive hormone levels. Although PBDEs have been banned in some countries, they do exist in our environment. Therefore, more studies are needed to reveal their potential toxicity and mechanisms, so as to monitor, predict and prevent their pollution. This review focuses on the male reproductive toxicity of PBDEs.

Molecular mechanism of ligand recognition by membrane transport protein, Mhp1.

The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1.

Potential biomarkers for monitoring the toxicity of long-term exposure to atrazine in rat by metabonomic analysis.

1. Herbicide atrazine (ATR) poses harmful effects on human health. The purpose of this study is to study potential biomarkers used for monitoring the toxic effects after chronic exposure to ATR by studying urine metabolites. 2. Rats were assigned into clinical chemistry and metabonomics arms, and each arm was divided into low-dose, high-dose and control groups. ATR was administered to rats along with their feed. At the end of 16, 20 and 24 weeks, clinical parameters and histopathologic changes was assessed to monitor the toxic effects. Twenty-four hour urine samples was analyzed by UPLC-MS, to find the significant alterations in metabolic profiling. 3. The body weight of rats in ATR group was lower than that of control starting from 12th week; abnormal levels of serum biochemistry and histopathologic alterations of organs were found initially from 16th and 20th week, respectively. Five exogenous and five endogenous metabolites were found which showed significant differences between ATR groups and control group at above-mentioned time points. 4. These metabolites may be used as potential indicators to monitor ATR toxicity, and also may provide some clues for understanding the mechanism of toxicity of ATR. The exact relationship between endogenous metabolites and ATR toxicity needs further investigation.

Applications of the BLEND Software to Crystallographic Data from Membrane Proteins.

X-ray diffraction from crystals of membrane proteins very often yields incomplete datasets due to, among other things, severe radiation damage. Multiple crystals are thus required to form complete datasets, provided the crystals themselves are isomorphous. Selection and combination of data from multiple crystals is a difficult and tedious task that can be facilitated by purpose-built software. BLEND, in the CCP4 suite of programs for macromolecular crystallography (MX), has been created exactly for this reason. In this chapter the program is described and its workings illustrated by means of data from two membrane proteins.

[High-frequency ultrasonography for diagnosis and differential diagnosis of acute scrotum in children].

OBJECTIVE: To analyze the high-frequency ultrasound image features of acute scrotum in children and explore the value of high-frequency ultrasonography in the diagnosis and differential diagnosis of the disease. METHODS: This retrospective study included 256 children aged 2 days to 14 years undergoing color Doppler ultrasonography at 2 hours to 3 days after onset of acute scrotum. We analyzed the morphology, internal echo and blood supply of the testis in comparison with the clinical and pathological results. RESULTS: Among the 256 cases, acute testicular torsion was found in 23, of which 16 were treated by complete resection the necrotic testis and the other 7 by surgical reduction of testicular torsion. Ultrasonographically, the involved testes presented different degrees of increase or decrease in volume, with uneven internal echoes, irregular hypoechoic flakes, and testicular hydrocele. Color Doppler flow imaging (CDFI) showed significant blood flow signals around the diseased testes but none within them. Acute testicular appendix torsion was found in 116 cases, in which ultrasonography manifested nodules with round or oval abnormal echoes between the upper pole of the testis and caput epididymidis, first hypoechoic and then gradually increased, heterogeneous internally. CDFI revealed enlarged epididymides and enriched testicular blood flow but no blood flow signals in the nodules. The 103 cases of acute epididymitis were ultrasonographically characterized by varied degrees of swelling of the involved epididymis with uneven internal echoes and rich blood flow signals on CDFI. Six of the cases were diagnosed as acute orchitis, with the ultrasonographic features of testicular swelling and low but uniform internal echoes, with rich blood flow signals on CDFI. Incarcerated inguinal hernia was confirmed in 15 cases, in which ultrasonography revealed intrusion of the hernia into the obviously enlarged scrotal sac with the mesentery and intestine in it, and blood flow visible on CDFI. Acute scrotal wall hematoma and edema was found in 8 cases, with the ultrasonographic characteristics of scrotal wall thickening, with visible blood flow signals on CDFI. CONCLUSIONS: High-frequency ultrasonography has a high sensitivity and specificity for acute scrotum in children, which can be applied as the first-choice clinical imaging modality and provide reliable evidence for the diagnosis and differential diagnosis of the disease.

[Response surface optimization of purification process for pigment from Coreopsis tinctoria by macroporous resins].

To optimize the purification process of pigments from Coreopsis tinctoria with macroporous resins by establishing second regression model with response surface methodology. The experiment showed that XDA-7 resin had the best purification effect for pigments from C. tinctoria. The optimal absorption conditions for pigments from C. tinctoria were determined as follows： concentration of pigments solution 2.7 g•L⁻¹, flow rate 6 mL•min⁻¹, pH 6. Under these conditions, the absorption rate of pigments was up to 94.16%. Optimal desorption conditions were as follows： ethanol concentration 64%, flow rate 5 mL•min⁻¹, elution dosage 4 BV. Under these conditions, pigment desorption rate was as high as 98.72%.

A simple solution hybridization rapidly detects DNA by fluorescent probe.

Traditional Southern blot, as the golden standard to detect DNA, is widely used in molecular biology. However, its operation process has some significant disadvantages, such as radioactive contamination, complex procedures, time-consuming. Some new methods developed in recent years need expensive equipments and also have the defects of complex procedures and time-consuming. The paper described a method to detect DNA quickly by liquid hybridization. The probe used is a fragment of DNA sequence labeled by FITC-12-dUTP. The whole process includes four steps: probe preparation, hybridization, electrophoresis and signal detection. The comparative experiments using the single strand DNA probe and the double strand DNA probe indicated that the sensitivity of single strand DNA probes, which could detect 0.38 µg (1.82 x 10(-13) mol) plasmid, is 2.1 times than that of the double strand DNA probes which could detect 0.8 µg (3.64 x 10(-13) mol) plasmid. The total procedure is simple and can be completed in 3 h.

[Primary study of arginine as feed attractants on Whitmania pigra].

The effects of the feed attractants on Whitmania pigra were studied. The average weight of Wh. pigra were 5.0 g. Arginine was selected as feed attractants, xanthan gum was selected as feed substrate. The times of Wh. pigra going into the inducing room were recorded. The water temperature was 22-25 degrees C during the whole experiment. Arginine that had better inducing effect was chosen to carry on in the gradient experiment. The results showed that the best inducing effect was found when the added amount of arginine was 0.3%, which was close to the arginine content of the natural body fluid of Wh. Pigra and Bellamya purificata, 2.97 mg x g(-1).

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

AIMS: The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. METHODS AND RESULTS: A two-stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5 year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. CONCLUSIONS: MitraClip + guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.