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Official websites use. Share sensitive information only on official, secure websites. This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Jie-Yu Pill JYP is a proprietary herbal medicine initially developed to treat menstrual mood disorders. This study sought to determine whether JYP could alleviate menopausal psychiatric symptoms in ovariectomized OVX mice, an animal model of estrogen deprivation, exposed to chronic unpredictable mild stress CUMS and the underlying mechanisms in comparison with estrogen therapy. These results suggest that JYP has comparable efficacy in ameliorating mood disorder-like behavior and cognitive impairment induced by a combination of estrogen deprivation and chronic stress in association with certain differential uterus-brain mechanisms compared to estrogen therapy. JYP may be a potential therapy for menopause-associated psychiatric disorders. Keywords: Jie-Yu Pill, herbal medicine, menopause syndrome, psychiatric disorders, estrogen deprivation, ovariectomized mice. Menopause is an important and physiological process in a woman's life, manifesting as the permanent cessation of menstruation due to the failure of ovarian follicular activity 1. Multiple psychiatric symptoms, including anxiety, depression, and cognitive decline, are frequent complaints of menopausal women and have become a significant obstacle to the quality of their life 1 , 2. Although estrogen therapy is the mainstay of the management of menopausal syndrome, its efficacy in improving psychiatric symptoms is limited and even controversial; long-term estrogen therapy even increases the risk of breast and ovarian cancer, stroke, and cardiovascular disease 3. Therefore, the development of novel treatment strategies for menopausal women is greatly desired. Jie-Yu Pill JYP , consisting of 10 herbal materials Table 1 , is a proprietary agent which was initially developed from classic Chinese medicine formulae to treat menstrual cycle related mood symptoms 4 , 5. Clinical studies have shown the effectiveness of JYP in the treatment of depressive and anxiety disorders, including climacteric depression, postpartum depression, generalized anxiety disorder, and psychosomatic disorders 4 , 6. A series of previous studies have confirmed anxiolytic and antidepressant effects of JYP in normal rodents and its modulatory effects on the hypothalamic-pituitary-adrenal HPA axis and monoamine neurotransmitters in the prefrontal cortex, hippocampus, and hypothalamus, the three brain regions that play key roles in the development of menopausal psychiatric disorders 7 — Individual Medicinal materials of the JYP formula a. On the other hand, one herbal medicine formula derived from JYP's two herbal materials, paeoniae radix and glycyrrhizae radix, could normalize dopamine hyperactivity induced female sex hormone dysfunction Several constituents contained in JYP, such as paeoniflorin 14 , saikosaponin A 15 , and polysaccharides of lily bulb Lilium lancifolium Thunb. Total polysaccharides of lily bulb and estrogen therapy exerted differential modulatory effects on different neurotrophins and estrogen receptor subtypes in the uterus and brain regions 16 , Brain neurotrophins modulate estrogen-associated learning, memory, and the underlying neuroplasticity 21 , We therefore hypothesized that JYP could produce comparable efficacy in alleviating menopause-related psychiatric disorders compared to estrogen therapy in association with differential mechanisms at peripheral reproductive organs and the brain. Ovariectomized OVX animals are often used as a model of estrogen deprivation as it is well-validated to represent most estrogen deprivation-associated clinical features in the adult human We have modified this model by exposing the OVX mice to chronic unpredictable mild stress CUMS to facilitate the development of mood disorder-like behavior and cognitive impairment 16 , The experimental time course is illustrated in Figure 1. After 1 week of acclimatization, animals received OVX or sham surgery and were allowed for 2 weeks of recovery. Our preliminary study found that OVX itself could not consistently evoke remarkable psychiatric disorder-like behavior. Chronic unpredictable mild stress CUMS procedure was then added to accelerate the development of mood disorder-like behavior and cognitive impairment. Multiple behavioral tests were carried out at 4 weeks post-OVX. Treatment started at 1 day after OVX and throughout 36 days. Experimental time course. Following small bilateral dorsal flank incisions, bilateral ovaries were removed immediately. An additional group of mice who received sham surgery with similar incisions but without ovary removal served as control. The animals received only one stressor per day and the same stressor was applied for no more than 2 consecutive days such that animals could not predict the occurrence of future stressor events. Our previous studies have confirmed that the addition of CUMS could better mimic distress experienced during menopause transition 16 , There were five treatment groups. The control group with sham surgery received vehicle treatment. All agents were delivered via oral gavage on a daily basis for 36 days. For estrogen treatment, E 2 Sigma-Aldrich, St. The dose of 0. JYP has been approved for marketing in China in The quality control of JYP adhered to the specifications and test procedures according to the internal standard. The two doses of JYP 2. Cognitive performance was measured using Morris water maze. Each mouse was placed on the surrounding zone and allowed to explore freely for 5 min under white fluorescent light from above. The total distance moved was analyzed to evaluate locomotor activity. The time spent in and number of entries into the central zone were obtained to evaluate the extent of anxiety. The maze is elevated to a height of 70 cm from the floor. The mouse was placed in the center area of the maze with its head directed toward an open arm and was then allowed to explore the maze freely for 5 min. Any subsequent visit to one of the four arms was counted when all four paws of a mouse entered. The time spent in and number of entries into the open arms were obtained to evaluate the extent of anxiety. On day 3, the position of the two bottles was switched for 24 h. At the end of the adaptation period, mice were deprived from food and water for 22 h. To prevent side preference in drinking behavior, the position of the two bottles was switched in the middle of testing. Water and sucrose consumption were measured as changes in weight of fluid consumed. A polycarbonate cylinder 30 cm in height and 20 cm in diameter was used for FST. A mouse was placed in the cylinder for 6 min and its movement was recorded on videotape. Immobility time, defined as the absence of all movements except for motions required to maintain the head above the water, was obtained from the last 4 min of the trial with EthoVision XT7 software. The test was conducted in a specially manufactured tail suspension box. Each mouse was suspended 50 cm above the floor of the box by fixing its tail tip 1 cm in length with adhesive tape. Immobility time, defined as the absence of any movements of limbs and trunk except for whisker movement and respiration, was recorded on videotape over 6 min of testing and analyzed with EthoVision XT7 software. The pool was conceptually divided into four quadrants, and a hidden platform 6 cm in diameter and 39 cm in height was placed in one of the quadrants and submerged 1 cm beneath the water surface. The test was divided into the two phases: 6 days of acquisition trials and 1 day of probe trial. For acquisition trials, at Day 1 the mice were allowed to freely swim in clear water with the visual cues on the hidden platform. During the subsequent 5 days, the mice were given four training trials per day in the milky water by placing titanium dioxide into the water. Different starting points were used on each of the five daily trials and the order of starting point was random. If a mouse located the platform, it was allowed to remain on the platform for 10 s. If a mouse failed to locate the platform within 60 s, it was placed on the platform for 10 s. The mice were towel-dried and returned to their home cage after each trial. The latency to the hidden platform was recorded from each training trial and averaged across the four training trials each day for data analysis. One mouse of the 5 JYP group died at Day 2 during the acquisition trials. The probe trial was conducted at Day 7. The platform was removed from the pool and a mouse was placed onto the pool and allowed to search the platform for 60 s. The total swimming distance was calculated to evaluate the locomotor activity. The latency to the target zone, the duration spent in the target zone, and the crossing number into the target zone were obtained to measure the spatial memory. A volume of 0. The uterus and whole brains were removed. The prefrontal cortex, hippocampus, and hypothalamus were dissected from the brains for Western blot analysis see below. Estradiol E 2 Cat No. The mobile phase consisted of acetonitrile A and 0. The flow rate was kept at 0. All tissues were centrifuged at 13, rpm for 20 min. The supernatant was collected and their protein concentration were measured with the Bradford method using Coomassie brilliant blue G Bio-Rad Laboratories Inc. The intensity of the bands was quantified by scanning densitometry using Image Lab 5. The mean value of the intensity was obtained from at least three independent experiments. Two-way repeated measure analysis of variance ANOVA was used to detect the effects of JYP on the latency to the hidden platform over acquisition trials. Between-group differences were further analyzed using Student—Newman—Keuls test. All statistical analysis was conducted with SAS version 9. Effects of 2. In the probe trial, representative individual swim paths from each group are shown in Figures 5B—F. E 2 treatment completely reversed OVX-induced changes in levels of the three hormones. JYP at 2. The contents of glutamate in the hypothalamus failed to be detected. The main purpose of this study was to evaluate the therapeutic effects of JYP as a novel therapy in improving mood and cognitive symptoms associated with menopause. In previous studies, we found that OVX alone could not constantly evoke anxiety- and mood disorder-like behavior; the addition of CUMS exposure however augmented aberrant behaviors 16 , This combination model also has been well-validated in several recent studies 28 — Indeed, in this study, OVX mice exposed to CUMS showed remarkable anxiety-like behavior, manifesting as marked decrease in time spent and number of entry in central zone of the open field and in open arms of EPM compared to the control group. The combination of OVX and CUMS further impaired spatial learning and memory ability, evidenced by strikingly longer latency in finding the platform in training trials and in reaching the target zone in the probe trial, and less duration and number of entry in the target zone than the control group in water maze test. These results, once again, confirm that OVX mice with stress exposure is a valid model in mimicking estrogen deprivation-induced psychiatric disorders. Treatment with JYP in particularly higher dose, however, suppressed anxiety- and depression-like behavior and prevent spatial learning and memory to a similar degree as did E 2 , suggesting comparable efficacy of JYP in the treatment of estrogen deprivation induced psychiatric disorders. This is also highly consistent with anxiolytic and antidepressant effects of JYP observed in male rodents with 10 , 11 and without exposure to CUMS 7 , 8. This study further revealed that the OVX mice exposed to stress displayed large weight gain and uterine shrinkage. Weight gain and shrinkage of the urogenital organs are the two major physical changes occurring during menopausal transition 31 , Such side effect has been widely observed in hormone replacement therapy in menopause women It seems that JYP has minor or even no effects on the uterus. It appears that, while JYP had comparable efficacy in improving estrogen deprivation-induced psychiatric symptoms, JYP may possess a better safety profile than estrogen therapy. In this study, we found that ovarian hormone deprivation evoked strikingly elevated serum levels of FSH and LH, which are indicative of ovarian failure, but exhausted blood estradiol level and hypothalamic GABA contents. OVX mice with stress exposure also exhibited markedly elevated serum levels of corticosterone CORT and ACTH, the two key stress hormones that play the crucial roles in the pathogenesis of menopausal anxiety and mood symptoms 19 , These results support the notion that estrogen deprivation caused anxiety and mood disorders may be derived from fluctuations in female sex hormones that result in altered GABAergic regulation of the HPA axis 19 , 37 , However, unlike E2, JYP did not affect blood estradiol level. GABA and glutamate are two key neurotransmitters that work together to maintain a balance between excitatory and inhibitory transmission in the brain Dramatic fluctuations in the levels of ovarian hormones during menopause transition profoundly disturbs this functional balance, causing pathological anxiety, mood, and cognitive disorders This study revealed that, in addition to the hypothalamic GABA, ovarian hormone deprivation plus stress exposure also exhausted GABA contents in the hippocampus and prefrontal cortex, but largely restored the glutamate contents and expression of its receptor NMDR1 in the two brain regions, probably causing an imbalance of opposite effects of the two amino acid transmitters. It seems that JYP may dominantly modulate glutamatergic neuronal functions in the brain regions associated with learning and memory. Neurotrophins play the crucial roles in the survival, maintenance, and regeneration of specific neurons as well as uterine growth and proliferation 41 — It therefore seems that increased risk of breast and endometrial cancer often occurred in estrogen therapy may be related to its enhancement effects on peripheral neurotrophins 48 , 49 , and the potential better safety profile of JYP observed in this study is, at least in part, derived from it tissue-specific effects on neurotrophins, particularly without effects on uterine neurotrophins. The two subtypes have distinct anatomical distribution patterns, different physiological processes in the brain and peripheral organs, and even counteract each other 53 , There have been contradictory studies on the effects of OVX on the expression of estrogen receptors in different brain regions 54 — In this study, we revealed that the removal of the ovaries caused a widespread suppression of the expression of the two receptor subtypes across the brain regions examined and the uterus. These results demonstrated that, like the tissue-specific effects of JYP on neurotrophins, the effects of JYP on the estrogen receptors also seem to be tissue-specific, i. The aberrant expression of estrogen receptors has been suggested to be associated with ovarian cancer, breast cancer, and other human cancers 57 — Therefore, the minor and even no effects of JYP on uterine estrogen receptors may be an additional factor contributing to the potential better safety profile of JYP observed in this study. Several limitations of this study should be considered. First, JYP as a whole preparation was evaluated in this study. We were unable to determine which individual materials or constituents play the principal roles in the psychotropic effects of JYP observed in this study. Further characterization of bioactive constituents of JYP could help better understand a phytochemical profile of this herbal agent, probably resulting in the discovery of novel constituents for treating estrogen deprivation-association disorders in particular psychiatric symptoms. Second, this study did not directly examine the beneficial effects of JYP in improving other estrogen deprivation-related symptoms, such as hot flush and night sweats. Previous studies have revealed the benefits of several herbal preparations in reducing hot flush in menopausal women 5. Finally, we did not consider the effects of the ovarian cycle in the sham mice as control group. Nevertheless, one recent study has shown that there were only differences in the severity of anxiety- and depression-like behavior in female C57BL mice across the estrous cycle Collectively, JYP has comparable efficacy in reducing psychiatric disorders observed in OVX mice exposed to stress with a better safe profile. The therapeutic advantages of JYP may be associated with certain uterus-brain mechanisms distinct from estrogen therapy. It deserves a clinical assessment as an alternative therapy in menopausal women with apparent psychiatric symptoms. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. X-DZ and Z-JZ were involved in the conception and design of the study, data analysis, and preparation of the manuscript. WS provided consultants and technical support. GC provided critical consultants on experiments and critical comments on the manuscript. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Front Psychiatry. Find articles by Xi-Dan Zhou. Find articles by Xin-Jing Yang. Find articles by Yu Zheng. Find articles by Zong-Shi Qin. Find articles by Wei Sha. Find articles by Gang Chen. Find articles by Zhang-Jin Zhang. Received Jul 4; Accepted Sep 29; Collection date Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. 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Buying Ecstasy online in Zhengzhou

Objective: The problems and challenges encountered by Chinese medical institutions in implementing the national centralized drug procurement was investigated and analyzed in order to provide reference for the regulatory agencies to formulate policies. Methods: A questionnaire survey was conducted to collect the problems encountered by Chinese medical institutions in implementing the national centralized drug procurement and the corresponding suggestions provided by relevant experts. Statistical analysis was performed to identify differences in the themes and the number of collected problems, further revealing the relevance to the region in which the medical institutions is located. Result: problems and suggestions were collected from Chinese medical institutions that located in North Furthermore, the content of gathered problems and suggestions involves in 15 themes including system construction, organizational system and work responsibilities, reasonable measurement and reporting of procurement volume et al. Conclusion: Chinese medical institutions are facing great challenges in implementing the national centralized drug procurement. The scientific study and judgment of the current situation and the construction of corresponding solution require a precise classification of the problems encountered by medical institutions in the process of implementing the national centralized drug procurement policy, which is of great practical significance for deepening the reform of the medical and health system. Increasing pharmaceutical expenditures is plaguing many countries worldwide Lopez Bastida et al. In order to reduce the pharmaceutical expenditures and standardize drug circulation, the Chinese government has implemented national centralized drug procurement NCDP since Moreover, national centralized drug procurement is being optimized and improved, gradually including the basic medical insurance drugs with bulk usage and procurement-volume and all types of clinical essential medicines with reliable quality Chinese Government. Public medical institutions are required to participate in the national centralized drug procurement and prioritize the use of drugs with national centralized procurement DNCP in accordance with clinical demands Gong et al. The application of NCDP has brought significant economic and social benefits and enhanced the rational use of clinical drugs, playing a positive effect on healthcare reform in China Chen et al. For instance, pharmaceutical expenditures and irrational clinical use rate were reduced comparison before and after NCDP policy Hu et al. Meanwhile, drug utilization and substitution rate of generic drugs significantly increased after policy intervention Xie et al. However, some problems have been disclosed in practicing NCDP by medical institutions, which significantly affected the effects of NCDP implementation. For example, lacking scientific estimation system resulted in large discrepancies between procurement volume and usage volume by medical institutions Xu. Due to the difficulty of securing drug supply in primary medical institutions, some drugs with national centralized procurement are in shortage or even out of supply, thus affecting clinical use of drugs Guo et al. Therefore, it is necessary and urgent to comprehensively understand the difficulties encountered by medical institutions in implementing the NCDP and provide corresponding solutions to promote the in-depth implementation of the national centralized drug procurement policy. To further improve the standardization of NCDP policy at medical institution level, several provinces and autonomous regions have issued expert consensus or recommendations on the implementation of NCDP in Chinese medical institutions Chen et al. This study aims to comprehensively reveal the problems encountered by Chinese medical institutions during implementing of NCDP policy and provide relevant recommendations given by experts, which is an important reference for the development of relevant policies. This study conducted a targeted survey of Chinese public medical institutions from 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government excluding Hong Kong, Macao and Taiwan. These medical institutions include provincial or university-affiliated hospitals, municipal, county and community health service centers. Meanwhile, participants, which belong to multiple disciplines or departments including pharmacy department, medical department, clinical department, medical insurance department, and medical quality control department, involved in this survey. After considerable discussion, the outline of the questionnaire was determined by the research committee. As is shown in Supplementary Table S1 , the questionnaire contains 6 primary catalogs which further subdivided into 15 secondary catalogs, involved the whole process of implementation of NCDP in medical institutions. Besides, open-ended questions included in each catalog intentionally, mainly for collection of the problems in the implementation of NCDP and corresponding suggestions. Subsequently, the questionnaires were directly conducted to medical institutions. These collected questions are categorized into 15 secondary categories. Regarding the handling of open-ended questions, they will be grouped under the 15 entries mentioned above. However, in case of disputes they will be further discussed by the research committee. Ultimately, these questionnaire results were further analyzed, summarized, and organized using statistical methods. IBM To examine the status of implementing of national centralized drugs procurement in Chinese medical institutions, this study conducted targeted research on Chinese medical institutions. The regional and hierarchical distribution of medical institutions were taken into full consideration. As shown in Table 1 , the regions of surveyed medical institutions were located North These investigated institutions contain the provincial or university-affiliated medical institutions Of note, a total of participants mainly distributed in department of pharmacy, medical, clinical, medical insurance, and medical treatment control, basically covering the essential departments for implementing national centralized drugs procurement. Among of these participants, pharmacy department presented largest number of personnel Taken together, this research not only reflects the actual situation of implementing of NCDP in different regions and levels of Chinese medical institutions, but also visualizes the problems encountered by the main enforcement departments of NCDP in medical institutions. In order to gain an in-depth understanding of the difficulties faced by Chinese medical institutions in implementation of national centralized drug procurement, the gathered problems and suggestions were further analyzed. As is shown in Table 3 , the content of compiled problems and suggestions could be categorized into 15 aspects covering the whole process of implementing NCDP in medical institutions, which revealed the fact that Chinese medical institutions are facing serious challenges in the implementation of NCDP. Statistical analysis revealed significant differences in the number of relevant problems and suggestions between the 15 categories. To illustrate the problems and suggestions under the various themes, the detailed enumeration of collected problems and suggestions is displayed in Table 4 ; Supplementary Table S2. In this study, questionnaires were distributed to Chinese medical institutions and collected problems and suggestions. Therefore, subsequent policy development and optimization should take regional differences into account. NCDP is a unique form of drug procurement in China, which playing a positive role in Chinese healthcare reform through reducing the prices of medicines and improving the rationality of clinical use of medicines. However, NCDP has gradually highlighted a number of typical problems and contradictions over the years, which have directly led to a reduction in the efficiency of the policy Gong et al. The questionnaires were distributed to Chinese medical institutions from North, Northeast, East, Central, South, Southwest, and Northwest China, which contains provincial, municipal, and community medical institutions. Meanwhile, this survey focused on multidisciplinary medical staff centered on pharmacy staff, which play a key role in the implementation of NCDP in medical institutions. Therefore, this study provides a more comprehensive and in-depth understanding of the current situation of NCDP in Chinese medical institutions. Furthermore, valid questionnaires and problems and suggestions were collected. These problems and suggestions cover the whole process of implementation of NCDP, indicating the Chinese medical institutions is facing great challenges in the execution of NCDP. There was statistically significant difference in the number of problems and suggestions between regions. Of these, the medical institutions coming from Southwest and Northwest regions have the highest average number of opinions and suggestions, probably due to the fact that these regions contain more remote areas, making it more difficult to implement the policy. The most suggested topics involve the clinical rational use of DNCP in medical institutions, including six aspects such as reasonable allocation of contract dosage, monitoring and analysis of completion progress, guarantee measures for clinical priority use, totaling articles In addition, a total of recommendations The results demonstrated that the rational clinical use and security of supply are still the most important concerns of medical institutions in the process of implementing the NCDP policy. Some medical institutions reflected that most varieties of the winning drugs were in short supply at the beginning of national centralized drug procurement and 1 to 2 months before the end of the procurement cycle, resulting in discontinuity of clinical treatment, and even some winning drugs were in short supply for a long time, such as acarbose tablets, celecoxib capsules and tenofovir disoproxil fumarate tablets Xu. Remote areas such as Tibet and Xinjiang lack drug manufacturers, and the vast majority of drugs are transported from the mainland Li, Yan, Bai, Li and Shao. In addition, icy roads in winter make drugs not available in time, which can further cause local drug shortages and stock-outs. At the same time, some drugs are used in remote areas in small quantities and cannot reach the minimum delivery quantity of the manufacturer, which can also lead to abnormal drug supply. These results are mainly the result of three reasons. First of all, there are problems with the production capacity of manufacturers for winning drugs. Some of winning drug manufacturers failed to fully anticipate the inaccuracy of the medical institutions to report the volume or exceed the agreed procurement volume, resulting in an oversupply Liu. Secondly, there are problems with distribution enterprises in the transportation of winning drugs Yang et al. According to the relevant documents, only one distribution enterprise is allowed for the winning drugs, but some of the distribution enterprises are small in scale with narrow distribution network, which affects the stability of the drug supply. Third, drug manufacturers control the sale of drugs in quantity and distribution. Some of the selected drug manufacturers who have completed the quantitative procurement of the winning drugs have controlled the distribution of drugs, resulting in tight supply or even shortage of drugs. In order to avoid the above problems, experts from the participating medical institutions suggest optimizing the management involved in the pre, in and post process. For the pre-event phase, the competent authorities in the tender to fully assess the supply capacity of drug manufacturers. The winning drugs have at least two distribution enterprises for medical institutions to choose. By increasing the supervision of drug distribution enterprises to achieve a smooth interface between the drug manufacturer and the distributor Tan et al. Because primary medical institutions in remote areas have less demand for drug use, which inevitably reduces the motivation of enterprises to distribute, the distribution rate of drugs in remote areas can be included as part of the qualification audit of distribution enterprises. In addition, medical institutions can make appropriate reserves of non-winning drugs before the start of a new batch of centralized procurement, leaving a buffer period of 1—2 months between procurement cycles. For the in-event phase, the competent departments regularly supervise drug manufacturers and distribution enterprises. Medical institutions establish contingency plans for shortages of DNCP, and report the production and distribution of the selected enterprises and distribution enterprises to the management. Collective drug procurement platform records the selected drug shortage information and vouchers, while the temporary procurement quantity is combined into the agreed procurement volume. For the post-event phase, the regulatory authorities can strengthen the monitoring and evaluation of the selected production enterprises, and include their production capacity, ability to guarantee supply and integrity into the assessment system. At the same time, it is recommended that specific penalty regulations be formulated at the national level to punish the consequences of default such as malicious bidding or inability to complete the procurement schedule after winning a bid, and failure to guarantee product quality after winning a bid. Increasing penalties at the national level can guide enterprises to bid wisely and strengthen the contractual spirit. The problems collected in this research cover the whole process of implementing NCDP by medical institutions, and some relatively concentrated problems cannot be solved by medical institutions on their own, which suggests that only continuous summary experience, comparative research and based on national conditions can consolidate and expand the results of NCDP. The deep-seated conflicts in the procurement process should be directly confronted and corresponding solutions proposed in order to achieve meeting the clinical demand for drugs, promoting rational drug management, optimizing hospital management, and forming a market-based price formation mechanism. Only by formulating scientific and reasonable policies, combining and forming synergy from medical insurance, medical treatment, medicine, and patients, can we break through the existing blind spots and blockages, ensure that drug procurement policies are gradually moving on a good and correct track, and realize the reform of the medical and health system to benefit the general public. All authors contributed to the article and approved the submitted version. This research was funded by management and service innovation major project of the first affiliated hospital of Wannan medical college Yijishan hospital of Wannan medical college , grant number CX The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Chen, L. The impacts of national centralized drug procurement policy on drug utilization and drug expenditures: the case of shenzhen, China. Public Health 17 24 , Chen, Y. China Med. Chinese Government, General Office of the State Council on promoting the normalization and institutionalization of centralized quantity procurement of drugs \[Jan 28\]. Beijing, China Office of the State Council. Google Scholar. Chinese Government, General Office of the State Council on the issuance of a pilot program for the centralized procurement and use of drugs by state organizations \[ Jan 17\]. Beijing, China: Office of the State Council. Chinese Pharmacists Association Consensus of Chinese experts on the precise management of national centralized drug volume-based procurement in medical institutions. New Drugs 32 3 , — Gong, X. Problems and countermeasures on the centralized drug procurement in large quantities in public hospitals. Guo, Z. A novel platform based on immobilized histidine tagged olfactory receptors, for the amperometric detection of an odorant molecule characteristic of boar taint. Health Policy 8 12 , 1—6. Hu, Q. Clinical application of meropenem and rationality of prescriptions before and after centralized procurement of antibacterial agents. Nosocomiology 32 6 , — Institute Report, Global medicine spending and usage trends outlook to Li, D. Research on the supply problems and countermeasures of national centralized drug procurement. Health Econ. Liu, Y. Problems and discussion on the implementation of national drug centralized procurement policy. China Health Stand. Lopez Bastida, J. Pharmaceutical expenditure in spain: cost and control. Health Serv. Smith, C. Retail prescription drug spending in the national health accounts. Health Aff. Hope 23 1 , — Sun, Q. Investigation on the factors affecting the supply security of bid-winning drugs in national drug volume-based procurement. Tan, Z. Researches on the legal risks of drug supply in public hospitals under the background of drug volume procurement and expansion and its countermeasures. Wan, Q. Influence of the national centralized drug procurement policy on clinical use of three anti-tumor drugs. China Pharm. Wang, Y. Xie, J. The influences of national centralized drug procurement policy on drug price, cost and generic drug substitution: taking the four municipalities data. Xu, Y. Supply status of bid-winning drugsin national volume-based procurement and supporting suggestions. Yang, Z. Establishment and application of dynamic evaluation system for drug distribution enterprises guided by drug adminstration management. Ye, D. Impact of the expert consensus on carbapenem consumption trends and patterns in public healthcare institutes: an interrupted time series analysis, Yuan, J. Lowering drug prices and enhancing pharmaceutical affordability: an analysis of the national volume-based procurement NVBP effect in China. Bmj Glob. Health 6 9 , Zhao, X. Impact of national centralized drug procurement policy on antiviral utilization and expenditure for hepatitis B in China. Hepatology 10 3 , — Zou, D. Analysis of the shortage of drugs in national centralized volume-based procurement and countermeasures and suggestions. Keywords: national centralized drug procurement, medical institutions, problems, challenge, China. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Drugs Outcomes Research and Policies. Problems and challenges encountered by Chinese medical institutions in implementing the national centralized drug procurement. Introduction Increasing pharmaceutical expenditures is plaguing many countries worldwide Lopez Bastida et al. Methods Research subjects This study conducted a targeted survey of Chinese public medical institutions from 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government excluding Hong Kong, Macao and Taiwan. Questionnaire design and data collection After considerable discussion, the outline of the questionnaire was determined by the research committee. Statistical methods IBM Results Characteristics of the surveyed medical institutions and respondents To examine the status of implementing of national centralized drugs procurement in Chinese medical institutions, this study conducted targeted research on Chinese medical institutions. TABLE 1. Characteristics of the medical institutions. TABLE 2. Distribution of the departments of the participants. TABLE 3. Thematic content distribution of problems and suggestions. TABLE 4. The model sample of collected problems and suggestions in major themes. TABLE 5. Regional distribution of collected problems and suggestions. TABLE 6. Regional distribution of problems in the supply of DNCP.

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