Vertically Stacked Transparent Organic Photodetectors for Light Intensity-Independent Wavelength Recognition.

Wavelength recognition is one of the important functions of photodetectors. However, wavelength recognition of the reported photodetectors generally depends on light intensity, which limits the practical applications. Here, a light intensity-independent wavelength recognition scheme based on vertically stacked transparent photodetectors is reported. By analyzing light intensity attenuation behavior in the multiple stacked photodetectors, the wavelength of incident light can be accurately determined. Due to the high transparency of the detectors, the multiple stacked detectors allow incident light to pass through. Meanwhile, since the attenuation coefficients at different wavelengths are attributed to the detector's absorption characteristics, the intensity of incident light and its wavelength can be determined by analyzing the attenuation coefficients measured through each stacked detector. Consistent wavelength values obtained at different light intensities verify the light intensity-independence of the multistacked detector system.

Drug shortages in China: a cross-sectional study.

BACKGROUND: Drug shortages significantly threaten public health and medical service provision worldwide. Research evidence on the complete picture of drug shortages is currently scant in China. This study aimed to provide a descriptive overview and a reference for alleviating of drug shortages in China. METHODS: National and provincial lists of drug shortages issued in China from 2018 to 2021 were collected and summarized. The information on essential medicines, medical insurance drugs, emergency drugs, and volume-based purchasing drugs was then matched with a drug shortage list to analyse the characteristics, proportion and incidence of drug shortage on each list based on the analysis of information such as dosage form, shortage frequency, and Anatomical Therapeutic Chemical (ATC) classification of the drugs in shortage. RESULTS: A total of 24 provinces issued drug shortages lists involving 408 drugs from 2018 to 2021. All 58 drugs in the national drug list were included on the provincial drug shortage list. Among all the drugs in shortage, the most significant shortage involved injections, accounting for 45.3% (185/408). Ninety-five drugs (23.3%) were in shortage 5 times (annual shortage > 1 time) or more in the provincial lists, and 199 drugs (48.8%) were on the shortage list only once. In terms of therapeutic property, nearly all categories of drugs had been reported in shortage, among which cardiovascular drugs, nervous system drugs, anti-tumor and immunomodulatory drugs, and blood and hematopoietic organ drugs accounted for more than 10%. There is no significant difference in drug shortage among economic regions. Comparing drugs in shortage and various lists, 81.9% (334/408), 51.0% (208/408) and 67.9% (277/408) fell on the National Medical Insurance Drug List, National Essential Medicines List, and WHO Model List of Essential Medicines, respectively, while the volume-based purchasing drugs accounted for 3.4% (14 drugs). The incidence of drug shortages on NEML, WHO Model List of Essential Medicines and medical insurance category A was significantly higher than that of medical insurance category B and volume-based purchasing drugs (P < 0.05). Of the Emergency Drugs List, 72.0% (36/50) also experienced shortages, significantly higher than all the above categories (P < 0.05). CONCLUSIONS: In China, drug shortages were severe and complicated. Drug shortages vary among economic regions but are not significant. In comparison, the national procurement pattern of volume-based drug purchasing may be conducive to alleviating the drug shortage problem. Collaboration of all partners was recommended to ensure the supply of clinically necessary drugs.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges.

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

Cost-Effectiveness of Evolocumab in Adult Patients with Atherosclerotic Cardiovascular Disease from Chinese Healthcare Perspective.

INTRODUCTION: To assess the cost-effectiveness of evolocumab with statins versus placebo combined with statins in the treatment of adult patients with atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) levels > 70 mg/dl after the maximum tolerable dose of statin therapy in China. METHODS: A Markov model, based on data from the FOURIER trial, claims databases, and published literature, was used to compare the health outcomes of the two therapies from the perspective of Chinese healthcare system. The time horizon in the model was a lifetime, the cycle length was a year, and the discount rate was 5%. The output indicators of the model included direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted on critical parameters such as cost, utility, and incidence of cardiovascular events to evaluate the effect of uncertainty in parameters and the robustness of the model. RESULTS: In Chinese adult patients with ASCVD and LDL-C levels > 70 mg/dl, evolocumab was associated with incremental QALYs of 1.25 and incremental costs of 18,714 CNY versus placebo, both with a statin therapy, resulting in an ICER of 14,969 CNY/QALY gained, which was less than the willingness to pay (WTP) threshold (80,976 CNY/QALY, a capita GDP of China, 2021). The result of one-way sensitivity analysis indicated that when the effect of evolocumab on myocardial infarction (MI) rate after the first year varied, ICER changed the most. The results of probabilistic sensitivity analysis showed that the probability of evolocumab added to statins being cost-effective at a threshold of 80,976 CNY/QALY was 100%. CONCLUSION: Compared with placebo and statin therapy combination, evolocumab added to statin therapy for adult patients with ASCVD and LDL-C > 70 mg/dl in China is cost-effective.

Effects of sacubitril/valsartan on life quality in chronic heart failure: A systematic review and meta-analysis of randomized controlled trials.

Aims: Sacubitril/valsartan has been demonstrated to have cardiovascular benefits in patients with chronic heart failure (CHF). We aimed to conduct a meta-analysis of its effects on life quality in patients with CHF, in comparison with the angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB). Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception through March 2022 for all relevant randomized controlled trials assessing the impact of sacubitril/valsartan and ACEI/ARB on health-related quality of life (HRQoL) in patients with CHF. Two reviewers independently conducted study selection, data extraction, and assessment of bias and quality of evidence. Review Manager 5.3 software was used for meta-analysis. Results: We included 10 clinical studies involving 10,426 patients with heart failure with reduced ejection fraction (HFrEF) and 7,689 patients with heart failure with preserved ejection fraction (HFpEF). Meta-analysis results showed that, in terms of the primary outcome, the sacubitril/valsartan group was superior than the ACEI/ARB group in improving HRQoL of HFrEF, and the difference was statistically significant (SMD 1.26; 95% CI: 0.14, 2.37; p = 0.03), while there was no significant difference between the two groups in HFpEF (SMD 0.37; 95% CI: -0.35, 1.09; p = 0.32). The effect of sacubitril/valsartan on the secondary outcome of the minimal important improvement rate of HRQoL in HFrEF was consistent with the primary outcome, while the effect in HFpEF was not clear. The descriptive analysis of individual studies indicated no significant difference in the improvement of 6-min walk distance between the two groups. Conclusion: Sacubitril/valsartan is beneficial to improve HRQoL outcome in patients with HFrEF with high quality of evidence. Compared with ACEI/ARB, sacubitril/valsartan was more effective. While in patients with HFpEF, this improvement was similar between the two groups.

Nanoscale Laser Metallurgy and Patterning in Air Using MOFs.

We report metallurgy on the nanoscale to generate metal nanoparticles and their simultaneous patterning in a single step. This is achieved by the self-reduction of porous metal-organic framework crystals using nanosecond pulsed laser irradiation. Metal nanoparticles of Fe, Co, Ni, Cu, Zn, Cd, In, Bi, and Pb with uniform sizes (controllable between 3 to 200 nm) and gaps (as narrow as 2 nm) are produced by nine different metal-organic frameworks, where atomically dispersed non-noble metal ions are reduced and gathered across the pores. The instant light absorption and cooling at local positions by a laser allows for precise and efficient patterning of metal nanoparticles. This new method is suitable for device fabrication at a speed of 15 mm2 s-1 on glass, consuming only 1.5 W of power. A large variety of metal nanoparticle three-dimensional architectures are demonstrated, among which one architecture exhibits an enhanced plasmonic effect homogeneously across the entire pattern for the detection of molecules at an extremely low concentration (10-12 M). These architectures are extremely stable under air and humidity during production, use, and storage, without altering the oxidation state, for 6 months.

Mesoporous Cages in Chemically Robust MOFs Created by a Large Number of Vertices with Reduced Connectivity.

We report the design and synthesis of two metal-organic frameworks (MOFs) with permanent porosity, MOF-818 and MOF-919, using a small ditopic organic linker, 1H-pyrazole-4-carboxylic acid (H2PyC), 0.4 nm in length. Three mesoporous cages of unprecedented polyhedra are identified in these MOFs, a wuh cage in MOF-818 and yys and liu cages in MOF-919, with diameters of 3.8, 4.9, and 6.0 nm, respectively. The ditopic H2PyC linker functions as the edge in the structure, while two types of metal-containing second building units (SBUs) function as the vertices. 28 vertices are present in the wuh cage; 50 in the yys cage; and 70 in the liu cage. Systematic analysis of these cages along with other mesoporous cages in supramolecules and MOFs constructed by ditopic linkers reveals that the extension of cage size is dictated by both the number and connectivity of the vertices. The increase in cage size is proportional to the number of vertices, while the growth rate is determined by their connectivity. The reduction in connectivity is found to be an effective way to create large cages. All three cages in this report are constructed by three-connecting (3-c) vertices and two-connecting (2-c) vertices. This [2-c, 3-c] connectivity represents the least connectivity required for the construction of cages and the most effective one for cage size expansion. The largest cage, liu, exhibits a cage size to linker size ratio of 15, outstanding in supramolecules and MOFs. MOF-818 is stable in water with a wide pH range (pH = 2-12), and the wuh cage is big enough for the inclusion of biomolecules such as vitamin B12 and insulin.

Nonplanar Monocyanines: Meso-Substituted Thiazole Orange with High Photostability and Their Synthetic Strategy as well as a Cell Association Study.

A convenient approach for the direct synthesis of meso-substituted thiazole orange (meso-TO) analogues has been unprecedentedly developed through the AlCl3-catalyzed reaction of parent TO with benzyl alcohol derivatives. Single-crystal X-ray structures show that the prepared new meso-TO analogues are nonplanar, forming a sharp contrast to planar TO. The spectral properties show that nonplanar meso-TO analogues do not aggregate, existing in monomer form (M) in PBS buffer, and have little effect of solvatochromism in different solvents. In comparison with the parents, meso-TO analogues exhibit a large Stokes shift, excellent light fastness, and inertness to singlet oxygen. A cellular association study demonstrates that incorporation of a benzyl group at the meso position methine of parent TO can decrease the cytotoxicity, change staining area in cells, and emit long-wavelength fluorescence for an extended time, which are useful for the development of smarter TOs for imaging in biological science.

[Analysis on the frequency of urinary iodine in a population-based intervention study].

OBJECTIVE: Through a two-year follow up program, this study was to analyze the urinary iodine frequency of a cohort in the intervention trial, concerning different doses of salt ionization, so as to explore the selection of appropriate concentration of salt ionization. METHODS: A multistage cluster sampling method was used to select three townships in two countries for community intervention with different doses [(15±5) mg/kg, (25±5) mg/kg, (35±5) mg/kg] of salt ionization. RESULTS: After intervention, the median of urinary iodine was reduced among the population. The urinary iodine frequencies of (15±5) mg/kg and (25±5) mg/kg among groups of children were mainly concentrated in 100-200 µg/L and 200-300 µg/L paragraphs in A county. While the 300 µg/L paragraph had an overall decline in B county, the 100 µg/L and 200 µg/L paragraph ratio increased but the trend seemed to be slow. The 100-300 µg/L paragraph of the four treatment groups took a larger proportion and kept smooth in a more ideal state. However, the control group still maintained at above 250 µg/L level. CONCLUSION: The iodine supplementation should be gradually implemented in Chongqing. The doses of salt ionization should be reduced from the current (35±15) mg/kg to (25±5) mg/kg in the economically developed areas. At the same time, we need to continuously follow the changes of the condition.

[Study on the change of urinary iodine of different salt concentrations among the target population in an intervention trial].

OBJECTIVE: To analyze the change of urinary iodine in a cohort of intervention trial and to observe the role of different doses on salt iodization and related impact factors on nutritional condition of iodine. METHODS: Multistage cluster sampling was used to sample three townships in two counties for community intervention with different doses (15 ± 5, 25 ± 5, 35 ± 5) mg/kg. RESULTS: Compared to the (35 ± 5) mg/kg group, the urine iodine levels of three experimental townships were gradually declining in county B when time went on, and the (15 ± 5) mg/kg group showed an obvious results, at 6, 12, 18 and 24 months, with the urine iodine level as 180.00, 186.10, 150.04, 191.28 µg/L respectively, which were in accordance with the WHO standard and reached to appropriate range (187.96 µg/L) at the 18 month. The townships at county Y under intervention had declined slightly, but the urine iodine levels did not reach the WHO standard. The thyroid volume declined from 3.65 ml to 3.40 ml in two counties and the difference between them was statistically significant. CONCLUSION: To some extent, reducing the iodine concentration in salt, had a role of lowering the urine iodine level and reducing the strumous rate.

Phospholipid conjugate for intracellular delivery of peptide nucleic acids.

Peptide nucleic acids (PNAs) have a number of attractive features that have made them an ideal choice for antisense and antigene-based tools, probes, and drugs, but their poor membrane permeability has limited their application as therapeutic or diagnostic agents. Herein, we report a general method for the synthesis of phospholipid-PNAs (LP-PNAs) and compare the effect of noncleavable lipids and bioreductively cleavable lipids (L and LSS) and phospholipid (LP) on the splice-correcting bioactivity of a PNA bearing the cell penetrating Arg9 group (PNA-R9). While the three constructs show similar and increasing bioactivity at 1-3 microM, the activity of LP-PNA-R9 continues to increase from 4-6 microM, while the activity of L-PNA-R9 remains constant and that of LSS-PNA-R9 decreases rapidly in parallel with their relative cytotoxicity. The activity of both LP-PNA-R9 and L-PNA-R9 dramatically increased in the presence of chloroquine, as expected for an endocytotic entry mechanism. The constructs were also found to have CMC values of 1.0 and 4.5 microM, respectively, in 150 mM NaCl, pH 7 water, suggesting that micelle formation may play a hitherto unrecognized role in modulating toxicity and/or facilitating endocytosis.