The impact of retirement on blood pressure: evidence from a nationwide survey in China.

INTRODUCTION: The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies. METHODS: From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement's causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups. RESULTS: Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants' SBP and pulse pressure as well as a possible decrease in female participants' blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement. CONCLUSION: Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future.

Uptake of hepatitis B antiviral treatment: A panel data analysis of 31 provinces in China (2013-2020).

BACKGROUND: China has made substantial efforts aimed to promote the uptake of antiviral treatment of hepatitis B (HB). It is unclear whether these policies achieved the desired impact. This study adopted medicines procurement data from 31 provinces to generate the first evidence about the number of standard antiviral treatment of HB overtime at both national and provincial levels in China. METHODS: We performed the panel data analyses and quasi-experimental design with the time-varying difference-in-difference method combined with the event study approach to estimate the uptake of HB antiviral treatment before and after national policy changes. RESULTS: The overall trends in HB antiviral treatment at the national level increased incrementally during 2013-2020. There was 2.8862 million 12-month (person-year) antiviral standard treatment in 2020, which was only 8.93% of the eligible people estimated to need treatment. The number of monthly antiviral standard treatment increased by 42.4% (p = .001) overall following the nationwide adoption of the '4 + 7' pilot-pooled procurement prices in 2019, which brought substantial price reduction of core antivirals. CONCLUSIONS: A low treatment rate is a critical issue in reaching the elimination of viral hepatitis as a public health threat in China. Affordability is an important but not the only factor that determines the uptake of hepatitis treatment. Further scaling up and acceleration of treatment uptake will need strategies improving public awareness of HB, strengthening diagnosis, linking people who are infected to chronic care, reducing loss to follow-up, and ensuring people who are eligible get timely treatment.

Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes.

Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410 nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.

Synthesis of N-Propargylsulfoximines by Copper-Catalyzed A3 -Couplings.

An efficient synthesis of N-propargylsulfoximines was developed through a copper-catalyzed coupling of aldehydes, alkynes, and NH-sulfoximines. The reaction requires no co-catalyst or ligand and shows a wide substrate scope with moderate to good yields.

Organocatalytic Asymmetric Synthesis of trans-γ-Lactams.

An N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective formal [3+2] reaction of o-hydroxy aromatic aldimines and cinnamaldehydes for the preparation of enantioenriched trans-γ-lactams was developed. An internal hydrogen bond between the o-hydroxy and the imine function was crucial for the reactivity and chemical selectivity. Trans-γ-lactam 3 d was easily oxidized to multifunctional 1,4-benzoquinone 8, which could further be transformed to biaryl 9 in the presence of a phosphoric acid. Finally, preliminary results for a kinetic resolution of (±)-trans-γ-lactam 3 d under asymmetric NHC catalysis are reported.

Organocatalytic Kinetic Resolution of Sulfoximines.

An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers of the sulfoximines can be obtained with excellent ee values (up to 99% ee and -97% ee, respectively). Performing the catalysis on a gram scale allowed using the recovered sulfoximine (+)-1j in an asymmetric synthesis of FXa inhibitor F.

Copper-Catalyzed S-C/S-N Bond Interconversions.

Under an atmosphere of dioxygen, copper-catalyzed de-alkylation/amination sequences provide sulfonimidamides from unprotected sulfoximines in moderate to good yields. Mechanistic studies suggest the involvement of radicals in both the C-S bond cleavage and the formation of the new N-S bond.

A modular chemoenzymatic cascade strategy for the structure-customized assembly of ganglioside analogs.

Gangliosides play vital biological regulatory roles and are associated with neurological system diseases, malignancies, and immune deficiencies. They have received extensive attention in developing targeted drugs and diagnostic markers. However, it is difficult to obtain enough structurally defined gangliosides and analogs especially at an industrial-relevant scale, which prevent exploring structure-activity relationships and identifying drug ingredients. Here, we report a highly modular chemoenzymatic cascade assembly (MOCECA) strategy for customized and large-scale synthesis of ganglioside analogs with various glycan and ceramide epitopes. We typically accessed five gangliosides with therapeutic promising and systematically prepared ten GM1 analogs with diverse ceramides. Through further process amplification, we achieved industrial production of ganglioside GM1 in the form of modular assembly at hectogram scale. Using MOCECA-synthesized GM1 analogs, we found unique ceramide modifications on GM1 could enhance the ability to promote neurite outgrowth. By comparing the structures with synthetic analogs, we further resolved the problem of contradicting descriptions for GM1 components in different pharmaceutical documents by reinterpreting the exact two-component structures of commercialized GM1 drugs. Because of its applicability and stability, the MOCECA strategy can be extended to prepare other glycosphingolipid structures, which may pave the way for developing new glycolipid drugs.

Uptake of hepatitis C direct-acting antiviral treatment in China: a retrospective study from 2017 to 2021.

BACKGROUND: Direct-acting antivirals (DAAs) for hepatitis C treatment in China became available since 2017. This study expects to generate evidence to inform decision-making in a nationwide scale-up of DAA treatment in China. METHODS: We described the number of standard DAA treatment at both national and provincial levels in China from 2017 to 2021 based on the China Hospital Pharmacy Audit (CHPA) data. We performed interrupted time series analysis to estimate the level and trend changes of the monthly number of standard DAA treatment at national level. We also adopted the latent class trajectory model (LCTM) to form clusters of the provincial-level administrative divisions (PLADs) with similar levels and trends of number of treatment, and to explore the potential enablers of the scale-up of DAA treatment at provincial level. RESULTS: The number of 3-month standard DAA treatment at national level increased from 104 in the last two quarters of 2017 to 49,592 in the year of 2021. The estimated DAA treatment rates in China were 1.9% and 0.7% in 2020 and 2021, which is far below the global target of 80%. The national price negotiation at the end of 2019 resulted in DAA inclusion by the national health insurance in January 2020. In that month, the number of treatment increased 3668 person-times (P < 0.05). LCTM fits the best when the number of trajectory class is four. PLADs as Tianjin, Shanghai and Zhejiang that had piloted DAA price negotiations before the national negotiation and that had explored integration of hepatitis service delivery with prevention and control programme of hepatitis C within the existing services demonstrated earlier and faster scale-up of treatment. CONCLUSIONS: Central negotiations to reduce prices of DAAs resulted in inclusion of DAA treatment under the universal health insurance, which are critical elements that support scaling up access to hepatitis C treatment in China. However, the current treatment rates are still far below the global target. Targeting the PLADs lagged behind through raising public awareness, strengthening capacity of the healthcare providers by roving training, and integrate prevention, screening, diagnosis, treatment and follow-up management of hepatitis C into the existing services are needed.

Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with phenols.

A novel iridium-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a variety of phenols was reported, which afforded the corresponding trans-2-phenoxy-1,2-dihydronaphthalen-1-ol products in high yields with moderate to excellent enantioselectivities (up to 98% ee) under mild conditions. The trans products are formed via the enantioselective cleavage of a bridgehead carbon-oxygen bond in 1 followed by S(N)2 nucleophilic attack by phenols. The effects of various bisphosphine ligands, Ag (I) salts, ammonium halides, bases, and solvents on the yield and enantioselectivity of the reaction were also investigated. The trans-configuration of the product 2a was confirmed by X-ray crystal structure analysis. A possible mechanism for the present catalytic reaction was proposed.

How Did Zero-Markup Medicines Policy Change Prescriptions in the Eyes of Patients?-A Retrospective Quasi-Experimental Analysis.

BACKGROUND: China implemented the zero-markup medicines policy to reverse the overuse of medicine in public health institutions, by changing the distorted financing mechanism, which heavily relies on revenue generated from medicines. The zero-markup medicines policy was progressively implemented in city public hospitals from 2015 to 2017. OBJECTIVE: This study is expected to generate convincing evidence with subjective measurements and contribute to a more comprehensive evaluation of the policy from both objective and subjective perspectives. METHODS: This study was based on a large patient-level dataset with a quasi-experimental design. We employed the difference-in-difference (DID) method, combined with propensity score matching methods, to estimate the causal effect of the policy in reducing overprescriptions from the patient perspective. RESULTS: The study estimated a statistically significant increased probability that the responded outpatients denied overprescription in their visiting hospitals. The mean interacted policy effect, in percentage points, of all observations were positive (logit DID model: 0.15, z = 10.27, SE = 0.01; PSM logit DID model: 0.15, z = 10.26, SE = 0.01; PSM logit DID hospital fixed-effect model: 0.12, z = 3.00, SE = 0.04). DISCUSSION: The policy might reduce overprescription in public hospitals from the patient's perspective. The patient's attitude is one aspect of a comprehensive policy evaluation. The final concrete conclusion of the policy evaluation can only be made through a systematic review of the studies with rigorous design and with both objective and subjective measurements.

A novel dual-channel fluorescent probe for selectively and sensitively imaging endogenous nitric oxide in living cells and zebrafish.

Nitric oxide (NO) plays various physiological and pathological roles in lots of biological processes. It is crucial to detect NO sensitively and selectively in vivo and in vitro as homeostasis of NO is closely related to various diseases. Herein, a novel dual-channel fluorescent dye (ENNH2) based on dicarboxyimide anthracene was developed as a highly sensitive and selective probe to detect NO in living systems using the dual-channel fluorescence. ENNH2 can emit bright red fluorescence due to the intramolecular charge transfer (ICT) from the amino group at the 6-position of 1,2-dicarboxyimide anthracene to the conjugated aromatic ring, and the ICT is effectively inhibited by the reductive deamination of the amino in the presence of NO to obtain the remarkable strong green emission with the excellent sensitivity (5.52 nM). Promisingly, ENNH2 exhibits an excellent performance in endogenous NO dual-channel fluorescence imaging of RAW 264.7 cells and zebrafish.

Eliminate Hepatitis C as a Public Health Threat: A Narrative Review of Strategies, Gaps, and Opportunities for China.

INTRODUCTION: As a country that is heavily burdened by hepatitis C, China's successful responses to this public health threat have significant implications for the achievement of the global elimination goal. METHODS: This article reviews China's strategies for prevention, screening, diagnosis, access to direct-acting antiviral agents (DAA) therapy, and patient management of hepatitis C. It also analyses the major challenges and summarizes the valuable successful international experiences that have implications for China to achieve the elimination goal. RESULTS: To promote the achievement of elimination, China has taken a series of proactive measures to promote the prevention and treatment of hepatitis C. Compared with other middle-income countries, there is still much room for China to achieve universal screening, diagnosis and treatment based on a streamlined disease management procedure. A stronger role of primary care in an integrated healthcare delivery system and integration of hepatitis C with other infectious disease programs should also be the focus of China's efforts. CONCLUSIONS: As a developing country with a large population, a "micro-elimination" strategy with focused screening and proactive diagnosis and treatment for the vulnerable population may be a more practical approach to eliminating hepatitis C in China. Continued efforts are needed to fully overcome the intellectual property barriers of sofosbuvir for forming the more competitive pan-genotype DAA combinations based on the locally developed DAAs. Meanwhile, the safety net for patients in economic hardship needs to be further strengthened. More importantly, it is necessary to promote patients' willingness and compliance with standard treatment through increased awareness of hepatitis C. The development of an integrated healthcare delivery system, a disease management procedure which is suitable for primary care, and full compliance of the primary care providers are also important to achieve effective cascade care management.

Factors associated with the uptake of biosimilars for breast cancer treatment from the perspectives of physicians and patients-Evidence from China.

Objective: To investigate the factors associated with the treatment of breast cancer with biosimilars from the perspectives of physicians and patients, and to generate evidence for promoting the uptake of biosimilars. Methods: This study targeted trastuzumab and its indicated human epidermal growth factor receptor 2 (HER2) positive breast cancer and included female HER2 positive breast cancer patients under treatment of trastuzumab at a provincial oncology medical center in southern China from 1 January 2021, to 31 December 2021. The study extracted patients' demographic, socioeconomic and clinical information and the basic information of their attending physicians from the hospital information system. We performed a bivariate multiple logistic regression analysis of predictive factors of the use of trastuzumab biosimilar. Results: A total of 446 patients (aged ranging between 26 and 74, 51.4 ± 9.06) were included in the analysis, and 19.1% chose biosimilar trastuzumab. Older patients, patients enrolled in the urban and rural resident health insurance program compared with those enrolled in the urban employee health insurance program, patients who initiated treatment after January 2021 when biosimilar entered clinical use compared with those who initiated treatment before, patients with female attending physicians, younger attending physicians and with chief attending physicians compared with deputy chief attending physicians were more likely to adopt biosimilar trastuzumab for treatment (p < 05). Controlling the other factors unchanged, when the patient's attending physician was deputy chief physician, increasing 1 year age of the patient was associated with an increased probability of adopting biosimilar by .8% (dy/dx = .008, 95%CI: .002-.01, p = .01). When the patient was aged between 26 and 60, the probability of adopting biosimilar for the patient whose attending physician was a chief physician was higher than for those whose attending physician was a deputy chief physician, and the gap was the largest when the patient was at the age of 45 (dy/dx = .20, 95%CI: .13-.27, p < .01). Conclusion: The uptake rate of biosimilars is still low at its initial development stage in China. Educational policies and physicians making recommendations to the indicated patients at the initiation stage of treatment are helpful to avoid reduced willingness to switch to biosimilars due to non-clinical reasons. Patients with lower ability-to-pay will have better accessibility to biologic regimens through the uptake of biosimilars. Official guidelines and professional training are critical to enhancing physicians' willingness and confidence in adopting biosimilars.

Impact of zero-mark-up medicines policy on hospital revenue structure: a panel data analysis of 136 public tertiary hospitals in China, 2012-2020.

OBJECTIVE: To quantify the overall and dynamic effects of the implementation of the zero-mark-up medicines policy on the proportionate revenue generated from medicines, medical services and government subsidies at Chinese tertiary public hospitals. METHODS: The revenue data of 136 tertiary public hospitals from 2012 to 2020 and the implementation-time framework of zero-mark-up medicines policy of these hospitals were obtained from the institutional survey of the third-party evaluation of the China Healthcare Improvement Initiative. The study adopted the time-varying difference-in-differences method and combined it with the event study approach to estimate the effects of the zero-mark-up medicines policy. RESULTS: Following the implementation of the policy, the proportionate medicines revenue decreased by 3.23% (p<0.001); the proportionate medical services revenue increased by 3.48% (p=0.001); and the difference in the proportionate government subsidies revenue was not significant. In the year of implementation, the proportion of revenue generated from medicines decreased by 7.76% (p=0.0148); and that from medical services increased by 8.62% (p=0.0167). The effect of the policy gradually strengthened thereafter. In 2020, the sixth year after some hospitals started the implementation of the policy, the share of revenue generated from medicines decreased the most by 18.43% (p=0.0151), and that generated from medical services increased the most by 15.29% (p=0.0219). The share of revenue generated from government subsidies increased by 2%-5% in the second, third, fifth and sixth years following implementation (p<0.05). CONCLUSIONS: Although the policy goal of adjusting hospital revenue structure has been achieved, the findings were insufficient to conclude whether the policy goal of establishing a scientific compensation mechanism was met by increasing the price of medical services and government input. Additionally, whether there was an unexpected policy effect requires further analysis.

What China can learn from Malaysia to achieve the goal of "eliminate hepatitis C as a public health threat" by 2030 - a narrative review.

Background: To discuss a range of strategic options for China to improve the accessibility of direct antiviral agents (DAAs) as the treatment for hepatitis C. Methods: We adopted a narrative review approach for comprehensive comparisons and in-depth analyses of the country context, and barriers of increasing the DAA treatment rate of hepatitis C in Malaysia and China, and how the two countries have been navigating the hepatitis C agenda. Findings: Malaysia adopted a series of successful strategies to scale up the diagnosis of hepatitis C and DAA treatment, which have valuable implications for China. Interpretation: The potential game-changing strategies for China to adapt from Malaysian experiences range from the stepping-up of political commitment and leadership, enhanced market competition, simplified and decentralized treatment at the strengthened primary care level, integrated healthcare services, coordinated government initiatives, to multi-organizational participation and civil society's active role in raising public awareness, and training of non-specialist physicians. Embarking on scale-up of hepatitis C treatment marks another contribution of China to improve the health of not only the Chinese citizens but also mankind, which is an important component for building healthy Chinese and global communities. Funding: No funding supported this study.

Exposure to DEHP or its metabolite MEHP promotes progesterone secretion and inhibits proliferation in mouse placenta or JEG-3 cells.

Di (2-ethyl-hexyl)phthalate (DEHP) is an environmental endocrine disruptor and commonly used as plasticizer. Maternal DEHP exposure during pregnancy reduces placental size and destroys placental structure. However, the underlying mechanisms were unclear. In this study, we supposed that DEHP disturbs endocrine function of placenta to inhibit the proliferation of placental cell. Using radioimmunoassay and ELISA, we found that DEHP and its active metabolite mono (2-ethyl-hexyl) phthalate (MEHP) promoted progesterone secretion in pregnant mouse and in JEG-3 cells, respectively. Therefore, placental endocrine function was altered by DEHP. The mRNA and protein level of progesterone synthetase 3ß-HSD1 was elevated by DEHP, which is conducive to the synthesis of progesterone. The level of progesterone receptor was down-regulated by DEHP and MEHP in mouse placenta and in JEG-3 cells, respectively. PR deficiency further promoted the level of 3ß-HSD1, which leads to a higher progesterone level. In turn, higher concentration of progesterone further inhibited the expression of PGR (PR gene). Therefore, higher progesterone down-regulated the level of its receptor PR. Meanwhile, decreased PR induced more progesterone secretion. There is a feedback loop between progesterone and PR. PR deficiency down-regulated the protein level of Cyclin D1 which plays an important role in cell proliferation. Accordingly, DEHP and its active metabolite MEHP can restrain proliferation of placental cell and disturb the progesterone secretion via decreasing the level of PR.

Mechanochemical Ruthenium-Catalyzed Hydroarylations of Alkynes under Ball-Milling Conditions.

Under solventless grinding conditions, mechanochemical ruthenium-catalyzed hydroarylations of alkynes with acetanilides lead to trisubstituted alkenes. Only catalytic amounts of pivalic acid or copper acetate are required, and without the need for external heating, the reaction times are shorter than those of their solution-based counterpart. Mechanochemical oxidative annulations through palladium-catalyzed intramolecular amination convert the products into N-acetylindoles.

Rhodium-Catalyzed [4 + 3] Annulations of Sulfoximines with α,ß-Unsaturated Ketones Leading to 1,2-Benzothiazepine 1-Oxides.

A Cp*Rh(III) complex has been used as catalyst for the preparation of unprecedented 1,2-benzothiazepine 1-oxides by [4 + 3] cyclization of NH-sulfoximines with α,ß-unsaturated ketones. For a wide range of substrates with various functional groups, moderate to good product yields were obtained.