OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Objective: To explore the relationship of sleep quality and emotional regulation difficulties in middle school students, and to analyze its mediating role of daytime dysfunction, social rejection and selfcontrol ability, so as to provide a scientific reference for improving middle school students mental health. Methods: From October to November, 2023, the Pittsburgh Sleep Quality Index, Adolescent Social Rejection Questionnaire, Brief Selfcontrol Scale and Difficulties in Emotion Regulation Scaleshort Form (DERS-16) were used to assess 806 students recruited from four middle schools in Bengbu City by a convenient cluster random sampling method. And model-6 of PROCESS and 5 000 Bootstraps were used to make a chainmediating model analysis. Results: Daytime dysfunction was positively correlated with sleep quality(r=0.57), social rejection(r=0.19), selfcontrol(r=0.29, P＜0.01). Selfcontrol was positively correlated with emotional regulation difficulties(r=0.54, P<0.01).Poor sleep quality showed a significant positive association with on daytime dysfunction, and daytime dysfunction further affected social rejection, selfcontrol ability and emotional regulation difficulties (β=0.86, 0.60, 1.27, 1.56, P<0.05). Meanwhile, daytime dysfunction, social rejection and selfcontrol played a serial mediating role in the relationship between sleep quality and emotional regulation difficulties (Estimate=0.11,95%CI=0.04-0.20,P<0.05). Conclusion The study reveals the complex relationship between sleep quality and emotional regulation difficulties in middle school students and provides a new theoretical basis for adolescent sleep improvement and mental health interventions.

OBJECTIVE To investigate the effect mechanism of andrographolide （Andro） on neuropathic pain （NP） in rats. METHODS Rats were randomly separated into sham operation group， model group， Andro low-dose （1 mg/kg）， Andro medium-dose （5 mg/kg） and Andro high-dose （10 mg/kg） groups， and sodium ferulic acid （150 mg/kg） group， with 12 rats in each group. Except for sham operation group， other groups used the chronic sciatic nerve compression injury method to induce NP model. After modeling， each group was given relevant dose of Andro intrathecally or sodium ferulate intragastrically. The sham operation group and model group were given a constant volume of normal saline once a day for 14 consecutive days. The mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） of rats were detected in each group after 7 and 14 days of administration. After the last medication， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， prostaglandin E2 （PGE2）， and substance P （SP） in rats were detected in each group， and the pathological morphology of spinal cord tissue was observed. mRNA and protein expressions of ionized calcium binding adaptor molecule-1 （Iba-1）， growth arrest specific protein 6 （Gas6）， and Axl in spinal cord tissue were determined. RESULTS Compared with model group， MWT and TWL after 7 and 14 days of the administration， the mRNA and protein expressions of Gas6 and Axl after the last medication were all increased significantly in administration groups （P＜0.05）， while the levels of IL-6， TNF-α， PGE2 and SP， mRNA and protein expressions of Iba-1 were all decreased significantly （P＜0.05）； pathological injuries such as the disordered arrangement of spinal cord neurons and dilation and congestion of capillaries had been alleviated to varying degrees. Compared with sodium ferulic acid group， there was no statistically significant difference in the above indicators in the Andro high-dose group （P＞0.05）. CONCLUSIONS Andro may inhibit inflammatory response by activating the Gas6/Axl signaling axis， thereby alleviating NP.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

BackgroundThe existing tools in China for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint do not sufficiently consider the specialty in psychiatric practice， and the scale items are somewhat cumbersome to use， which together restrict their further promotion and application. Accordingly， there is an urgent need for developing a more scientific assessment tool. ObjectiveTo construct a scale for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint and to verify its reliability and validity， so as to provide a generic tool for the assessment. MethodsBased on the theoretical framework of the knowledge-attitude-practice model， the preliminary scale was formed through systematic literature review， qualitative interview and Delphi method. From July to December 2021， a stratified sampling was utilized to select 729 psychiatric nurses from tertiary， secondary and primary （including unclassified medical institutions and grassroots hospitals） psychiatric hospitals in Guangdong Province. The formal scale was developed through item analysis， exploratory factor analysis and confirmatory factor analysis. The validity of the scale was evaluated by content validity and structure validity， and the reliability was verified by procedures including Cronbach's α coefficient， test-retest reliability， and split-half reliability. ResultsA total of 12 items of three dimensions （knowledge， attitude， practice） were included in the scale for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint. The scale-level content validity index （S-CVI） was 0.941， and the item-level content validity index （I-CVI） ranged from 0.812 to 1.000. Exploratory factor analysis extracted three common factors， and the cumulative variance contribution rate was 62.948%. The confirmatory factor yielded adequate fit. Cronbach's α coefficient was found to be 0.887 for the scale， 0.819 for knowledge dimension， 0.842 for attitude dimension， and 0.831 for practice dimension. The split-half reliability and test-retest reliability for the scale were 0.712 and 0.922， respectively. ConclusionThe scale shows satisfactory reliability and validity， which can be used to assess psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint. ［Funded by Guangdong Clinical Teaching Base Teaching Reform Research Project （number， 2021JD119）］

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.