Microcomb-driven silicon photonic systems.

Microcombs have sparked a surge of applications over the past decade, ranging from optical communications to metrology1-4. Despite their diverse deployment, most microcomb-based systems rely on a large amount of bulky elements and equipment to fulfil their desired functions, which is complicated, expensive and power consuming. By contrast, foundry-based silicon photonics (SiPh) has had remarkable success in providing versatile functionality in a scalable and low-cost manner5-7, but its available chip-based light sources lack the capacity for parallelization, which limits the scope of SiPh applications. Here we combine these two technologies by using a power-efficient and operationally simple aluminium-gallium-arsenide-on-insulator microcomb source to drive complementary metal-oxide-semiconductor SiPh engines. We present two important chip-scale photonic systems for optical data transmission and microwave photonics, respectively. A microcomb-based integrated photonic data link is demonstrated, based on a pulse-amplitude four-level modulation scheme with a two-terabit-per-second aggregate rate, and a highly reconfigurable microwave photonic filter with a high level of integration is constructed using a time-stretch approach. Such synergy of a microcomb and SiPh integrated components is an essential step towards the next generation of fully integrated photonic systems.

Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin : A Multi-database Cohort Study.

BACKGROUND: Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins. However, evidence on their efficacy and safety during actual use is limited. OBJECTIVE: To compare the real-world effectiveness and safety of rosuvastatin and atorvastatin. DESIGN: Active comparator cohort study using target trial emulation. SETTING: The China Renal Data System (CRDS) and UK Biobank (UKB) databases. PARTICIPANTS: Adults newly prescribed rosuvastatin or atorvastatin. MEASUREMENTS: The primary outcome was all-cause mortality. Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching. RESULTS: Among the 285 680 eligible participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of -1.03% (95% CI, -1.44% to -0.46%) in the CRDS database and -1.38% (CI, -2.50% to -0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for major adverse cardiovascular events and major adverse liver outcomes. In the UKB database, the risk for development of type 2 diabetes mellitus was higher with rosuvastatin, and the 2 medications carried similar risks for development of chronic kidney disease and other statin-related adverse effects. LIMITATION: Possible residual confounding. CONCLUSION: This study found differences in risks for some important outcomes associated with rosuvastatin and atorvastatin. The differences were relatively small, and many did not meet traditional standards for statistical significance. Further research is needed to understand whether these findings can be used with confidence in clinical practice. PRIMARY FUNDING SOURCE: National Key R&D Program of China and National Natural Science Foundation of China.

Renin-angiotensin system inhibitors and risk of hepatocellular carcinoma among patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. METHODS: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. RESULTS: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). INTERPRETATION: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.

Detecting Neonatal AKI by Serum Cystatin C.

SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.

Use of Histologic Parameters to Predict Glomerular Disease Progression: Findings From the China Kidney Biopsy Cohort Study.

RATIONALE & OBJECTIVE: Challenges in achieving valid risk prediction and stratification impede treatment decisions and clinical research design for patients with glomerular diseases. This study evaluated whether chronic histologic changes, when complementing other clinical data, improved the prediction of disease outcomes across a diverse group of glomerular diseases. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 4,982 patients with biopsy-proven glomerular disease who underwent native biopsy at 8 tertiary care hospitals across China in 2004-2020. NEW PREDICTORS & ESTABLISHED PREDICTORS: Chronicity scores depicted as 4 categories of histological chronic change, as well as baseline clinical and demographic variables. OUTCOME: Progression of glomerular disease defined as a composite of kidney failure or a ≥40% decrease in estimated glomerular filtration rate from the measurement at the time of biopsy. ANALYTICAL APPROACH: Multivariable Cox proportional hazard models. The performance of predictive models was evaluated by C statistic, time-dependent area under the receiver operating characteristic curve (AUROC), net reclassification index, integrated discrimination index, and calibration plots. RESULTS: The derivation and validation cohorts included 3,488 and 1,494 patients, respectively. During a median of 31 months of follow-up, a total of 444 (8.9%) patients had disease progression in the 2 cohorts. For prediction of the 2-year risk of disease progression, the AUROC of the model combining chronicity score and the Kidney Failure Risk Equation (KFRE) in the validation cohort was 0.76 (95% CI, 0.65-0.87); in comparison with the KFRE model (AUROC, 0.68 [95% CI, 0.56-0.79]), the combined model was significantly better (P = 0.04). The combined model also had a better fit, with a lower Akaike information criterion and a significant improvement in reclassification as assessed by the integrated discrimination improvements and net reclassification improvements. Similar improvements in predictive performance were observed in subgroup and sensitivity analyses. LIMITATIONS: Selection bias, relatively short follow-up, lack of external validation. CONCLUSIONS: Adding histologic chronicity scores to the KFRE model improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases. PLAIN-LANGUAGE SUMMARY: Risk prediction and stratification remain big challenges for treatment decisions and clinical research design for patients with glomerular diseases. The extent of chronic changes is an important component of kidney biopsy evaluations in glomerular disease. In this large multicenter cohort including 4,982 Chinese adults undergoing native kidney biopsy, we evaluated whether histologic chronicity scores, when added to clinical data, could improve the prediction of disease prognosis for a diverse set of glomerular diseases. We observed that adding histologic chronicity scores to the kidney failure risk equation improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases.

Positive association of triglyceride-glucose index with new-onset hypertension among adults: a national cohort study in China.

BACKGROUND: Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults. METHODS: A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension. RESULTS: The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0-6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07-1.55, Q2; aHR, 1.24, 95% CI 1.03-1.49, Q3; aHR, 1.50, 95% CI 1.22-1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04-1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose-response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension. CONCLUSIONS: High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Ultra-compact hybrid plasmonic mode convertor based on unidirectional eigenmode expansion.

An ultra-compact hybrid plasmonic mode convertor is demonstrated based on a hybrid plasmonic slot waveguide structure. Benefiting from the unidirectional eigenmode expansion approach, a mode-interference-based ${{\rm TE}_{00}}$TE00-to-${{\rm TM}_{01}}$TM01 mode convertor is realized for the first time, to the best of our knowledge, with an ultra-compact footprint of only ${2}.{33} \times {7}\,\,\unicode{x00B5} {{\rm m}^2}$2.33×7µm2. At the wavelength of 1550 nm, the insertion loss is below 2.34 dB, and the extinction ratio is 25.6 dB with mode conversion purity as high as 94.6%. The extinction ratio is over 15.5 dB for the entire C-band with a bandwidth of extinction ratio above 10 dB larger than 110 nm. The transmissivity of the crosstalk ${{\rm TE}_{10}}$TE10 and ${{\rm TE}_{02}}$TE02 at 1550 nm is $ - {16.1}$-16.1 and $ - {22.7}\,\,{\rm dB}$-22.7dB, respectively.

Stereoselectively Assembled Metal-Organic Framework (MOF) Host for Catalytic Synthesis of Carbon Hybrids for Alkaline-Metal-Ion Batteries.

Cost-effective metal-based nanostructured hybrids have been widely dedicated to potential energy storage and conversion applications. Herein, we develop a facile methodology for the synthesis of precise carbon-confined hybrid nanostructures by stereoselective assembly accompanied by catalytic pyrolysis. Polyacrylonitrile fiber films favors not only metal-polymer coordination, but also oriented assembly to ensure the well-defined nanostructure of the carbon hybrids. During chemical vapor deposition (CVD), cobalt-nanoparticle-catalyzed growth of carbon-nanotube branches driven by organic molecules (e.g. melamine) delivers hierarchical carbon hybrids. The resulting carbon hybrids exhibit outstanding electrochemical performance for metal-ion batteries, for example, a high specific capacity of 680 mAh g-1 after 320 cycles (Li-storage) and 220 mAh g-1 after 500 cycles (Na-storage) without decay.

Chlorinated Azaphilone Pigments with Antimicrobial and Cytotoxic Activities Isolated from the Deep Sea Derived Fungus Chaetomium sp. NA-S01-R1.

Four novel compounds, chaephilone C (1), chaetoviridides A-C (2-4), were obtained from the culture of a deep sea derived fungus Chaetomium sp. NA-S01-R1, together with four known compounds-chaetoviridin A (5), chaetoviridine E (6), chaetomugilin D (7) and cochliodone A (8). Their structures, including absolute configurations, were assigned based on NMR, MS and time-dependent density functional theory (TD-DFT) ECD calculations. A plausible biogenetic pathway for compounds 1-3 was proposed. Compounds 2 and 3 exhibited antibacterial activities against Vibrio rotiferianus and Vibrio vulnificus. Compounds 1, 3 and 4 displayed similar anti-methicillin resistant Staphylococcus aureus (anti-MRSA) activities in comparison to chloramphenicol. Compound 2 showed the most potent cytotoxic activities towards the Hep G2 cell and compounds 1 and 3 demonstrated relatively stronger cytotoxic activities than the other compounds against the HeLa cell.

Post-treatment level of LDL cholesterol and all-cause mortality in patients with atherosclerotic cardiovascular disease: evidence from real-world setting.

AIMS: This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C ≥ 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality. CONCLUSION: Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.

Intensive control of LDL cholesterol (LDL-C) has been widely recommended for cardiovascular (CV) protection in patients with atherosclerotic CV disease. Nevertheless, a U-shaped association between LDL-C levels and all-cause mortality has been noted in several general population studies, prompting concerns regarding the safety of intensive lipid control. In this multicentre cohort comprising 33 968 patients at the highest CV risk, we found that patients with lower post-treatment LDL-C level were at lower risk of both all-cause and CV mortality, and this survival benefit was unaffected by intensity of LDL-C reduction, types of lipid-lowering agents, and other clinical characteristics.

Kidney function-specific cut-off values of high-sensitivity cardiac troponin T for the diagnosis of acute myocardial infarction.

Background: The diagnosis of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin T (hs-cTnT) remains challenging in patients with kidney dysfunction. Methods: In this large, multicenter cohort study, a total of 20 912 adults who underwent coronary angiography were included. Kidney function-specific cut-off values of hs-cTnT were determined to improve the specificity without sacrificing sensitivity, as compared with that using traditional cut-off value (14 ng/L) in the normal kidney function group. The diagnostic accuracy of the novel cut-off values was validated in an independent validation cohort. Results: In the derivation cohort (n = 12 900), 3247 patients had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Even in the absence of AMI, 50.2% of participants with eGFR <60 mL/min/1.73 m2 had a hs-cTnT concentration ≥14 ng/L. Using 14 ng/L as the threshold of hs-cTnT for diagnosing AMI led to a significantly reduced specificity and positive predictive value in patients with kidney dysfunction, as compared with that in patients with normal kidney function. The kidney function-specific cut-off values were determined as 14, 18 and 48 ng/L for patients with eGFR >60, 60-30 and <30 mL/min/1.73 m2, respectively. Using the novel cut-off values, the specificities for diagnosing AMI in participants with different levels of kidney dysfunction were remarkably improved (from 9.1%-52.7% to 52.8-63.0%), without compromising sensitivity (96.6%-97.9%). Similar improvement of diagnostic accuracy was observed in the validation cohort (n = 8012). Conclusions: The kidney function-specific cut-off values of hs-cTnT may help clinicians to accurately diagnose AMI in patients with kidney dysfunction and avoid the potential overtreatment in practice.

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia.

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.

Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

BACKGROUND: Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. METHODS: The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. RESULTS: Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). CONCLUSIONS: ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

High-coherence parallelization in integrated photonics.

Coherent optics has profoundly impacted diverse applications ranging from communications, LiDAR to quantum computations. However, developing coherent systems in integrated photonics comes at great expense in hardware integration and energy efficiency. Here we demonstrate a high-coherence parallelization strategy for advanced integrated coherent systems at minimal cost. By using a self-injection locked microcomb to injection lock distributed feedback lasers, we achieve a record high on-chip gain of 60 dB with no degradation in coherence. This strategy enables highly coherent channels with linewidths down to 10 Hz and power over 20 dBm. The overall electrical-to-optical efficiency reaches 19%, comparable to that of advanced semiconductor lasers. This method supports a silicon photonic communication link with an unprecedented data rate beyond 60 Tbit/s and reduces phase-related DSP consumption by 99.99999% compared to traditional III-V laser pump schemes. This work paves the way for realizing scalable, high-performance coherent integrated photonic systems, potentially benefiting numerous applications.

Association between mean arterial pressure and clinical outcomes among patients with heart failure.

AIMS: Mean arterial pressure (MAP) is widely used for evaluating organ perfusion, but its impact on clinical outcomes in patients with heart failure (HF) remains poorly understood. The aim of this study is to investigate the relationship between MAP and all-cause mortality and readmission in patients with HF. METHODS AND RESULTS: We retrospectively analysed data from PhysioNet, involving 2005 patients with HF admitted to Zigong Fourth People's Hospital between 2016 and 2019. The primary outcomes were composite outcomes of all-cause mortality and readmission at 3 and 6 months. The secondary outcomes were readmission at 3 and 6 months. Multivariate-adjusted Cox regression models, restricted cubic spline curves (RCS), and propensity score matching (PSM) were used to explore the relationship between MAP and clinical outcomes. Among 2005 patients with HF [≥70 years, 1460 (72.8%); male, 843 (42.0%)], the incidence of primary outcome at 3 months was 33.4% (223/668), 24.4% (163/668), and 22.7% (152/669), and at 6 months, it was 47.5% (317/668), 38.5% (257/668), and 38.0% (254/669) across MAP tertiles [from Tertile 1 (T1) to Tertile 3 (T3)], respectively. The RCS showed an 'L-shaped' relationship between MAP and primary or secondary endpoints. Multivariate-adjusted Cox models showed that a higher MAP was significantly associated with a lower risk of composite endpoints at 3 months [adjusted hazard ratio (aHR) 0.75, 95% confidence interval (CI) 0.61-0.92, P = 0.006, Tertile 2 (T2); aHR 0.69, 95% CI 0.56-0.86, P = 0.001, T3] and 6 months (aHR 0.79, 95% CI 0.67-0.93, P = 0.005, T2; aHR 0.77, 95% CI 0.64-0.91, P = 0.003, T3) compared with T1. After 1:1 PSM, the effect of maintaining a relatively higher MAP was slightly attenuated. Threshold analyses indicated that per 10 mmHg increase in MAP, there was a 21% and 14% decrease in composite endpoints at 3 and 6 months, respectively (aHR 0.79, 95% CI 0.69-0.91, P = 0.001), and 6 months (aHR 0.86, 95% CI 0.77-0.97, P = 0.013) in patients with MAP ≤ 93 mmHg. The associations were consistent in readmission (secondary outcomes), various subgroups, and sensitivity analysis. CONCLUSIONS: A higher MAP was associated with a lower risk of a composite of all-cause mortality and readmission. Maintaining a relatively higher MAP could potentially improve the clinical prognosis for patients with HF.

Harnessing microcomb-based parallel chaos for random number generation and optical decision making.

Optical chaos is vital for various applications such as private communication, encryption, anti-interference sensing, and reinforcement learning. Chaotic microcombs have emerged as promising sources for generating massive optical chaos. However, their inter-channel correlation behavior remains elusive, limiting their potential for on-chip parallel chaotic systems with high throughput. In this study, we present massively parallel chaos based on chaotic microcombs and high-nonlinearity AlGaAsOI platforms. We demonstrate the feasibility of generating parallel chaotic signals with inter-channel correlation <0.04 and a high random number generation rate of 3.84 Tbps. We further show the application of our approach by demonstrating a 15-channel integrated random bit generator with a 20 Gbps channel rate using silicon photonic chips. Additionally, we achieved a scalable decision-making accelerator for up to 256-armed bandit problems. Our work opens new possibilities for chaos-based information processing systems using integrated photonics, and potentially can revolutionize the current architecture of communication, sensing and computations.

Slow-light silicon modulator with 110-GHz bandwidth.

Silicon modulators are key components to support the dense integration of electro-optic functional elements for various applications. Despite numerous advances in promoting the modulation speed, a bandwidth ceiling emerges in practices and becomes an obstacle toward Tbps-level throughput on a single chip. Here, we demonstrate a compact pure silicon modulator that shatters present bandwidth ceiling to 110 gigahertz. The proposed modulator is built on a cascade corrugated waveguide architecture, which gives rise to a slow-light effect. By comprehensively balancing a series of merits, the modulators can benefit from the slow light for better efficiency and compact size while remaining sufficiently high bandwidth. Consequently, we realize a 110-gigahertz modulator with 124-micrometer length, enabling 112 gigabits per second on-off keying operation. Our work proves that silicon modulators with 110 gigahertz are feasible, thus shedding light on its potentials in ultrahigh bandwidth applications such as optical interconnection and photonic machine learning.

Epidemiology and outcomes of post-AKI proteinuria.

Background: Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Methods: This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Results: Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Conclusions: Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

BACKGROUND: The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. METHODS: A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. RESULTS: Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. CONCLUSIONS: Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.