Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

OBJECTIVE: To investigate the correlation between nucleated red blood cell (NRBC) level on the first day of intensive care unit (ICU) admission and 28-day mortality in adult septic patients, and to evaluate the value of NRBC as an independent predictor of death. METHODS: Single-cell transcriptomic analysis was performed using the GSE167363 dataset from the Gene Expression Omnibus (including 2 healthy controls, 3 surviving septic patients, and 2 non-surviving septic patients). A retrospective clinical analysis was conducted using the America Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including adult patients (≥ 18 years) with first-time admission who met the Sepsis-3.0 criteria, excluding those without NRBC testing on the first ICU day. The demographic information, vital signs, laboratory test indicators, disease severity score and survival data on the first day of admission were collected. The restricted cubic spline (RCS) curve was used to determine the optimal cut-off value of NRBC for predicting 28-day mortality in patients. Patients were divided into low-risk and high-risk groups based on this cut-off value for intergroup comparison, with Kaplan-Meier survival curve analysis conducted. Independent risk factors for 28-day mortality were analyzed using Logistic regression and Cox regression analysis, followed by the construction of regression models. RESULTS: NRBC were detected in the peripheral blood of septic patients by single-cell transcriptomic. A total of 1 291 sepsis patients were included in the clinical analysis, with 576 deaths within 28 days, corresponding to a 28-day mortality of 44.6%. RCS curve analysis showed a nonlinear relationship between the first-day NRBC level and the 28-day mortality. When NRBC ≥ 1%, the 28-day mortality of patients increased significantly. Compared to the low-risk group (NRBC < 1%), the high-risk group (NRBC ≥ 1%) had significantly higher respiratory rate, heart rate, sequential organ failure assessment (SOFA), and simplified acute physiology score II (SAPSII), and significantly lower hematocrit and platelet count. The high-risk group also had a significantly higher 28-day mortality [49.8% (410/824) vs. 35.5% (166/467), P < 0.05], and shorter median survival time (days: 29.8 vs. 208.6, P < 0.05). Kaplan-Meier survival curve showed that compared with the low-risk group, the survival time of high-risk group was significantly shortened (Log-rank test: χ ² = 25.1, P < 0.001). After adjusting for potential confounding factors including body mass, temperature, heart rate, respiratory rate, mean arterial pressure, serum creatinine, pulse oximetry saturation, hemoglobin, hematocrit, Na⁺, K⁺, platelet count, and SOFA score, multivariate regression analysis confirmed that NRBC ≥ 1% was an independent risk factor for 28-day mortality [Logistic regression: odds ratio (OR) = 1.464, 95% confidence interval (95%CI) was 1.126-1.902, P = 0.004; Cox regression: hazard ratio (HR) = 1.268, 95%CI was 1.050-1.531, P = 0.013]. CONCLUSIONS NRBC ≥ 1% on the first day of ICU admission is an independent risk factor for 28-day mortality in septic patients and can serve as a practical indicator for early prognostic assessment.
Humans ; Sepsis/blood* ; Intensive Care Units ; Risk Factors ; Retrospective Studies ; Prognosis ; Male ; Female ; Hospital Mortality ; Middle Aged ; Aged

Objective:To evaluate the safety and efficacy of hydroxyapatite-magnesium (HA-Mg) glaucoma drainage plate after implantation in rabbit eyes.Methods:Twelve New Zealand white rabbits were randomly assigned to HA-Mg drainage implant group and trabeculectomy group using the paired comparison method, with 6 rabbits in each group.The right eyes of rabbits were taken as the experimental eyes, and the left eyes of rabbits were taken as a normal control group.HA-Mg drainage implant group underwent implantation of the HA-Mg drainage plate and the trabeculectomy group underwent trabeculectomy.At 1, 3, and 5 months after surgery, the ocular condition was observed by slit-lamp examination with auxiliary lenses and the fixation of the drainage plate in the anterior chamber and subconjunctiva was measured by ultrasound biomicroscopy.At 5 months after surgery, corneal endothelial cell counts were performed with a corneal endothelial cell counter.The intraocular pressure (IOP) was continuously measured weekly for 21 weeks preoperatively and postoperatively.The flow patency of aqueous humor drainage channel was identified by the injection of trypan blue in anterior chamber.The aqueous humor drainage channels and surrounding tissues were evaluated by hematoxylin-eosin (HE) staining after HA-Mg drainage plate was completely degraded.This study was in accordance with China Animal Welfare Law and the ARVO Statement on the use of animals for ophthalmic research, and animal experiments were conducted in accordance with the Regulations on the Administration of Experimental Animals issued by the National Science Council.The study protocol was reviewed and approved by the Ethics Committee of The Third Affiliated Hospital of Chongqing Medical University (No.Kelun Pre-Examination [2021]14).Results:No systemic or ocular side effects were observed in the experimental animals after surgery.All 6 HA-Mg drainage plates were completely degraded about 4 months postoperatively, among which 4 plates were well-fixed and 2 plates had a minimal rotation, and no plate moved into the anterior chamber.At 5 months after surgery, the number of corneal endothelial cells in the HA-Mg drainage implant group and normal control group was 2 535.2±274.4 and 2 521.0±175.8, respectively, and there was no statistical significance between them ( t=0.073, P=0.857).There were statistically significant differences in IOP among the three groups at different time points before and after surgery ( Fgroup=26.409, P<0.001; Ftime=7.843, P<0.001), in which the IOP in trabeculectomy group and normal control group at different time points after surgery was higher than that in HA-Mg drainage implant group, and the IOP in HA-Mg drainage implant group at different time points after surgery was lower than that before surgery (all at P<0.05).The patency test revealed that the trypan blue could still drain from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation.The scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded 6 months postoperatively, and no obvious inflammatory cell infiltration was seen. Conclusions:After implantation of HA-Mg drainage plate in rabbit eyes, the intraocular pressure can be effectively lowered and the safety is good.

Objective To explore the expression and clinical value of serum calprotectin and toll like receptor 2(TLR2)with type 2 diabetic kidney disease(DKD).Method According to the levels of UACR,90 T2DM patients treated in our hospital from January 2019 to January 2022 were divided into normal albuminuria group(Con,UACR<30 mg/g),microalbuminuria group(Micro,UACR 30～300 mg/g),and macroalbuminuria group(Macro,UACR>300 mg/g),30 cases per group.Result The levels of BMI,HbAlc,calprotectin,TLR2,and NLRP3 increased sequentially from Con,Micro to Macro groups(P<0.05),while eGFR in the Macro group was lower than that in the Con or Micro groups(P<0.05).Pearson correlation analysis showed that serum calprotectin was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01);NLRP3 is positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,SUA,and UACR(P<0.01),and negatively correlated with eGFR(P<0.01);TLR2 was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr and UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01).Multiple linear regression analysis showed that FPG,HbAlc,TC,Scr,calprotectin,and TLR2 were the influencing factors of UACR.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve for diagnosing DKD with serum calprotectin and TLR2 was 0.883 and 0.961,with sensitivities of 73.33%and 96.67%,and specificity of 100.00%and 83.33%.Conclusion Serum calprotectin and TLR2 are closely related to the occurrence and development of DKD.The diagnostic value of TLR2 for DKD is superior to serum calprotectin.

Objective:To investigate the correlation between impulse oscillometry system examination indicators and conventional pulmonary ventilation function.Methods:The pulmonary ventilation function data of 10 883 patients from January 1, 2020 to December 31, 2022 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were included. The one-second rate [ratio of forced expiratory volume in the first second (FEV 1) to forced vital capacity (FVC)] measured as a percentage of the predicted value was ≥92% for the control group ( n=3 478) and <92% for the pulmonary obstruction group ( n=7 405). The obstruction group was subdivided into five groups according to the degree of pulmonary dysfunction: mild group ( n=3 938),moderate group ( n=1 142),oderate-severe group ( n=917),severe group ( n=737),and extremely severe group ( n=671). Conventional pulmonary ventilatory function FVC, FEV 1, one-second rate, and forced expired flow at 50% of FVC (MEF50%), forced expired flow at 75% FVC (MEF25%), maximal mid-expiratory flow (MMEF), peak expiratory flow (PEF), and pulsed oscillation pulmonary function test were detected in both groups of patients. Impedance at 5 Hz (Z5) means total respiratory resistance, resistance at 5 Hz (R5) means total airway resistance, reactance at 5 Hz (X5) indicates the elastic recoil of the peripheral airways, and resistance at 20 Hz (R20) represents resistance of the central airways. R5-R20 reflects resistance in the small airways. Additionally, peripheral resistance (Rp), respiratory resonance frequency (Frex), and area under the reactance curve (Ax) were also measured. Correlation between the indicators of the two groups and the sensitivity and specificity of the impulse oscillometry system parameters for the diagnosis of obstructive pulmonary ventilation dysfunction were analyzed. Results:Pulmonary function force expiratory volume in the first second as a percentage of predicted value (FEV 1%Pre) [80.10 (54.95,97.10)%],one-second rate [62.43(48.67, 67.02)%],MEF50% [1.33 (0.62,1.97)L/s],MEF25% [0.28 (0.17,0.41)L/s], MMEF [0.85 (0.43,1.29)L/s],and PEF [5.64 (3.73,7.50)]L/s in the obstruction group were significantly lower than those in the control group ( P<0.05). The differences within the subgroups of the obstruction group were also significant ( P<0.05). Pulsed oscillation Z5 [0.42 (0.33,0.55)kPa·L -1·s -1],Rp [0.25 (0.20,0.45)kPa·L -1·s -1], R5 [0.39 (0.31,0.49)kPa·L -1·s -1], R20 [0.28 (0.24,0.34)kPa·L -1·s -1], R5-R20 [0.09 (0.05,0.17)kPa·L -1·s -1],Frex [16.32 (13.07,20.84)Hz], and Ax [0.67 (0.28,1.64)] indices in the obstruction group were significantly higher than those in the control group. X5 [-0.14 (-0.23, -0.10)kPa·L -1·s -1] was significantly lower than that in the control group ( P<0.05). Z5, Rp, X5, R5, R5-R20, Frex, and Ax were statistically significant between different degrees of obstruction in the obstruction group ( P<0.05). The impulse oscillometry system parameters Z5, Rp, R5, R20, R5-20, Frex, and Ax were negatively correlated with the indices of conventional pulmonary ventilation ( r=-0.21-0.68, P<0.05), and the parameter X5 was positively correlated with the indices of conventional pulmonary ventilation ( r=0.41-0.68, P<0.05). The pulsed oscillation pulmonary function test parameters X5 (58.60%-95.68%) and Ax (57.08%-98.06%) presented the best sensitivity; X5 (86.29%-98.82%), Frex (86.69%-94.71%), and Ax (88.10%-98.53%) displayed the best specificity; and R20 presented the worst sensitivity and specificity. The sensitivity and specificity were slightly better in female patients than in male patients. Conclusion:The technical parameters of the impulse oscillometry system showed significant correlation with relevant indices of conventional pulmonary ventilation function detection. These well reflect the changes of different degrees of pulmonary ventilation function and have greater significance for reference in evaluating the degree of pulmonary function impairment.

Objective:To investigate the role and mechanism of molecular hydrogen in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Balb/c male mice were randomly(random number) divided into control group, control+H 2, LPS and LPS+H 2 group with 6 mice in each group. The levels of malondialdehyde (MDA) and Fe 2+ in lung tissue were detected by kits. The lung tissue morphology was observed. The infiltration levels of F4/80 positive macrophages in lung tissue were detected by immunofluorescence staining. A549 cells were divided into control, control+H 2, erastin and erastin+H 2 group. The reactive oxygen species (ROS), malondialdehyde, (MDA), lactate dehydrogenase (GSH), number of cell death and lactate dehydrogenase (LDH) release in each group were detected by kits. Nrf2, GPX4, and HO-1mRNA were quantified by real-time PCR, the protein expression level of Nrf2 was detected by western blot, and the nuclear translocation level of Nrf2 was observed by immunofluorescence. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups. Results:Compared with the control group, the histopathological damage was aggravated, and the levels of MDA, Fe 2+ significantly increased in the LPS group, and F4/80 positive immune cells infiltration significantly increased (all P<0.05). Compared with LPS group, the degree of lung injury in LPS+H 2 group significantly reduced (all P<0.05). In vitro experiments, compared with the control group, the ROS, MDA levels, number of cell death and LDH release significantly increased in erastin group (all P<0.05), while GSH, and GPX4 mRNA levels decreased (all P<0.05). HO-1mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Compared with erastin group, ROS, MDA levels, cell death number and LDH release decreased in earstin+H 2 group (all P<0.05). The levels of GSH, GPX4 mRNA, Nrf2 mRNA, HO-1 mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Conclusions:Molecular hydrogen attenuates LPS-induced ALI by promoting Nrf2 nuclear translocation to inhibit ferroptosis of alveolar epithelial cells.

Objective To explore the current status of post-traumatic stress disorder(PTSD)symptoms among military officers at high altitude,determine the effects of childhood trauma experiences on the symptoms,and investigate the role of parent-child alienation in the process.Methods A cross-section study was conducted on 238 male military officers at high altitude subjected with cluster sampling.All of them were surveyed with childhood trauma question(CTQ),inventor of alienation toward parents(IAP),and Post-traumatic Stress Disorder Checklist(PCL-C)in October 2021.Then the mediating effect of parent-child alienation on childhood trauma and PTSD symptoms was investigated.Results ①The prevalence of PTSD-positive symptoms was 8.5％among the military officers at high altitude.②The prevalence of PTSD-positive symptoms was 15.6％for the military officers with childhood trauma,which was significantly higher than that of those without childhood trauma(5.1％,Chi-square=7.27,P＜0.01).③ PTSD symptoms,childhood trauma experiences and parent-child alienation were significantly positively correlated with each other(r=0.35～0.76,P＜0.01).④ Both childhood physical abuse(β=1.05,P＜0.001)and parent-child alienation(β=0.39,P＜0.01)could positively predict the severity of PTSD symptoms for them.⑤Parent-child alienation played a partial mediating role in the association between physical abuse and PTSD symptoms(β=1.16,95％CI:0.54～1.75).Conclusion Military officers at high altitude with childhood trauma have a higher prevalence of PTSD-positive symptoms and more severe symptoms.Childhood physical abuse can not only directly affect PTSD symptoms,but also indirectly affect its severity through parent-child alienation.