“Can We Break Through the Identity Dilemma?”: The Multiple Governance, Identities Conflict, and Self-Managements for Chinese PWUD.

Background: Exploring why the national drug policy failed is an important issue. Based on it, this study considers both the drug governance system and the voice of people who use drugs (PWUD) to analysis drug policy effects and the lives of PWUD in the Chinese context. Methods: This study takes PWUD living in urban communities as the research participants. Using qualitative research data, exploring how individual using drug experiences are identified and classified by structural forces and how individuals manage their daily life. Results: The study finds that law enforcement agencies (Narcotics Control Office (NCO), Police Station , and Community Assistance Group (CAG)) have different attitudes toward PWUD and generate different managements, forming multiple governance models, and then shaping the multiple identity dilemma. PWUD perceive the dilemma, and they adopt the strategies of spatial isolation (hidden flow), disconnection from experience (temporal isolation), and instrumental cooperation to continuously re-adjust and achieve identity recovery from the bottom-up. Conclusion/importance: Through evaluating the effectiveness of self-management strategies, this research integrates the Chinese drug rehabilitation situation, expands the specific performance of law enforcement system, and presents the limitations and positive value of self-management strategies.

Drug Knowledge Extraction Framework with Entity Pair Calibration for Chinese Drug Instructions

Existing pharmaceutical information extraction research often focus on standalone entity or relationship identification tasks over drug instructions. There is a lack of a holistic solution for drug knowledge extraction. Moreover, current methods perform poorly in extracting fine-grained interaction relations from drug instructions. To solve these problems, this paper proposes an information extraction framework for drug instructions. The framework proposes deep learning models with fine-tuned pre-training models for entity recognition and relation extraction, in addition, it incorporates an novel entity pair calibration process to promote the performance for fine-grained relation extraction. The framework experiments on more than 60k Chinese drug description sentences from 4000 drug instructions. Empirical results show that the framework can successfully identify drug related entities (F1 >= 0.95) and their relations (F1 >= 0.83) from the realistic dataset, and the entity pair calibration plays an important role (~5% F1 score improvement) in extracting fine-grained relations.

Imaginary Penalty and Identity Conflict: The Dilemma and Strategies of Multiple identities in Substance Abusers in Chinese Drug Policy

Background: Exploring why the national drug policy failed is an important issue. Although the theory of "Imaginary Penalty" points out the relationship between ideology and policy-making, it ignores the systemic nature of drug control and the voice of drug addicts. Methods: This study takes substance abusers who live in urban communities as the research participants. Using qualitative research data, this study explores how individual drug abuse experiences are identified and classified by structural forces and how individuals manage their daily life. Results: The study finds that law enforcement agencies (Narcotics Control Office (NCO), Police Station , and Community Assistance Group (CAG)) have different attitudes toward Substance abusers and generate different managements, forming multiple governance models, and then shaping the multiple and incomplete Substance abusers’ identity dilemma. Drug addicts perceive the dilemma, and they adopt the strategies of spatial isolation (hidden flow), disconnection from experience (temporal isolation), and instrumental cooperation to continuously re-adjust and achieve identity recovery from the bottom up with the "possible citizens" narrative logic. Conclusion/importance: Through evaluating the effectiveness of self-management strategies, this research integrates the Chinese drug rehabilitation situation, expands the specific performance of "Imaginary Penalty" in the law enforcement system, and presents the limitations and positive value of self-management strategies.

Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade

Background Podocytes have become a crucial target for interventions in proteinuric kidney diseases. Many studies have reported that overexpression of transient receptor potential cation channel protein 6 (TRPC6) in podocyte injury upregulates intracellular Ca2+ influx and stimulates Ca2+-dependent protease calpain-1 signaling. The traditional Chinese drug, tetrandrine, a nonselective Ca2+ channel blocker, has long been used to treat chronic kidney disease. This research aimed to explore the possible mechanisms underlying the anti-proteinuric properties of tetrandrine. Methods We investigated the involvement of tetrandrine in Ca2+ dependent calpain-1 signaling in mouse podocytes and adriamycin-induced nephropathy rats. Cyclosporine A (CsA) and U73122 were used as positive controls. Cell viability, cytotoxicity, Ca2+ concentration, calpain activity, and mRNA and protein expression levels of calpain-1 signaling pathways were examined. The clinical and pathological changes were measured. Results Tetrandrine decreased intracellular Ca2+ influx in cultured TRPC6-overexpressing podocytes. In both in vitro and in vivo studies, the administration of tetrandrine downregulated calpain activity and the expression of calpain-1 and restored the expression of downstream Talin-1 and nephrin. Compared to CsA, tetrandrine treatment exhibited superior inhibitory effects on calpain activity and calpain-1 expression. Conclusions Tetrandrine has therapeutic potential in podocyte damage by blocking Ca2+-dependent activation of the calpain-1 signaling pathway. Tetrandrine reduced proteinuria, improved renal function, and alleviate renal pathological damage.

Atezolizumab Plus Chemotherapy vs. Chemotherapy in Advanced or Metastatic Triple-Negative Breast Cancer: A Cost-Effectiveness Analysis

Purpose: The IMpassion130 trial demonstrated the efficacy of adding atezolizumab to paclitaxel for advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of adding atezolizumab to nab-paclitaxel for TNBC from the perspective of Chinese health sector.Methods: A partitioned survival model was implemented for patients with TNBC. The survival data were derived from IMpassion130 trial. Direct costs and utility values were collected from the Chinese Drug Bidding Database and published literatures. The primary analysis outcomes were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to observe model stability.Results: In the base-case analysis, the ICER of atezolizumab plus nab-paclitaxel vs. nab-paclitaxel is respectively, $176,056/QALY, $118,146/QALY, and $323,077/QALY in the ITT, PD-L1(+) and PD-L1(–) group.Conclusion: Adding atezolizumab to nab-paclitaxel could improve survival time significantly in the PD-L1-positive group, but it is not a cost-effective strategy compared to nab-paclitaxel monotherapy for Chinese patients with advanced or metastatic triple-negative breast cancer in the current economic context of China.

The Financial Impact of Patents on SMEs in China: Empirical Evidence from Pharmaceutical Sector

With the disruptive technology innovation time arrival, small and medium-sized enterprises (SMEs) have been the motor of innovation and played an increasingly major role in national economic development. As the shift towards an ‘open innovation’ paradigm, awareness of intellectual property rights has increased, and patents have been an important tool for Chinese pharmaceutical enterprises. Considering its mass production of low-level generic drugs, there are still many arguments about its lack of innovation. This article aims to identify if and how patents, as essential indicators of innovation, generate financial performance measured by SMEs in the pharmaceutical sectors. Patent data are a vital source of competitive intelligence. A positive association was found between annually added patents and gross sales. Many other patent indicators, such as the number of forward citations and patent transfer, were statistically significant. Moreover, the results suggested that there was a one-year lag between patent publication and financial performance. A series of patent quantity and quality indicators have shown significant effects on the financial performance of Chinese pharmaceutical enterprises. These patents generate a positive financial impact, which builds up a solid basis for keeping sustainable innovation capability in the Chinese drug industry.

The impacts of Chinese drug volume-based procurement policy on the use of policy-related antibiotic drugs in Shenzhen, 2018–2019: an interrupted time-series analysis

Background In 2019, Chinese government implemented volume-based procurement of 25 drugs in 4 municipalities and 7 sub-provincial cities, i.e. “4 + 7” policy. Competitive bidding was conducted by the government based on the annual agreed procurement volume submitted by each public medical institution in pilot cities. Pilot cities were required to implement bid winning results in March 2019 and the use volume of bid winning products was examined to ensure the completion of agreed procurement volume. In the policy, an oral antibiotic (cefuroxime) was included. Given the current condition of the irrational use of antibiotics in China, this study aims to evaluate the impact of “4 + 7” policy on the use of policy-related antibiotics. Methods This study used drug purchase data from the Centralized Drug Procurement Survey in Shenzhen 2019, covering 24 months from January 2018 to December 2019. Oral antibiotic drugs related to “4 + 7” policy were selected as study samples, including cefuroxime and 12 antibiotic drugs that have an alternative relationship with cefuroxime in clinical use. Purchase volume and expenditures were selected as outcome variables, and were measured using Defined Daily Doses (DDDs) and Chinese yuan, respectively. Segmented linear regression analysis with interrupted time series was adopted to examine the effect of “4 + 7” policy. Results After the implementation of “4 + 7” policy, the overall volume of cefuroxime and its alternative drugs increased from 9.47 million DDDs to 13.42 million DDDs, with an increase of 41.8 %. The results of segmented linear regression showed that the volume of cefuroxime significantly increased 161.16 thousand DDDs after “4 + 7” policy (95 % CI: 59.43 to 262.90, p-value = 0.004). The volume of alternative drugs significantly increased 273.65 thousand DDDs (95 % CI: 90.17 to 457.12, p-value = 0.006). The overall “4 + 7” policy-related antibiotics significantly increased 436.31 thousand DDDs (95 % CI: 190.81 to 681.81, p-value = 0.001) after “4 + 7” policy. Conclusions This study provides evidence that the implementation of “4 + 7” volume-based procurement policy was associated with significant increases in the volume of policy-related antibiotic drugs. The increase in antibiotic use after the policy needs special attention and vigilance.

A Multi-Site Cross-Sectional Study of Anxiety Symptoms and the Associated Factors Among Chinese Drug Users Undergoing Compulsory Detoxification Treatment

Compulsory drug detoxification treatment (CDT) is currently the major drug rehabilitation modality in China, and drug users often suffer from extraordinary levels of stress during CDT, leading to a high prevalence of anxiety symptoms. This study assesses anxiety symptoms of the drug users undergoing CDT and explores the associated factors. A cross-sectional study with cluster sampling was conducted in three cities in Liaoning Province of Northeast China. Nine hundred CDT drug users were interviewed face-to-face with Chinese questionnaires. Hierarchical multiple regression (HMR) analysis was conducted to explore the factors associated with anxiety symptoms. The prevalence of anxiety symptoms among the CDT drug users was substantially high (33.2%). HMR analysis indicated perceived stress and characteristics of drug use such as types of drugs, were the most important contributors to anxiety symptoms. Optimism (LOT-R) played a protective role in reducing anxiety symptoms in this population. Anxiety symptoms of drug users undergoing CDT were present in a significant proportion of the CDT population. Optimism is a protective factor which could attenuate the detrimental effects of perceived stress on anxiety symptoms and potentially improve treatment outcomes.

Synergistic Effects of Cryptotanshinone and Senkyunolide I in Guanxinning Tablet Against Endogenous Thrombus Formation in Zebrafish

Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Salvia miltiorrhiza Bunge and Ligusticum striatum DC. are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based in vivo fluorescence screening, we demonstrated the synergistic effects between S. miltiorrhiza Bunge and L. striatum DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels via multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.