Human midbrain organoids: a powerful tool for advanced Parkinson's disease modeling and therapy exploration.

Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra. Despite progress, the pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as a promising model for studying PD, drug screening, and potential treatments. This review discusses the development of hMLOs, their application in PD research, and current challenges in organoid construction, highlighting possible optimization strategies.

4,5-Diamino-2-Thiouracil-Powered Dual-Mode Biosensor for Sensitive, Nonenzymatic Determination of Saliva Uric Acid Levels.

Nonenzymatic and rapid monitoring of uric acid levels is of great value for early diagnosis, prevention, and management of oxidative stress-associated diseases. However, fast, convenient, and low-cost uric acid detection remains challenging, especially in resource-limited settings. In this study, a novel and rapid biosensing approach was developed for the simultaneous visualization and quantification of uric acid levels by using the unique surface plasmon resonance and photothermal property of 4,5-diamino-2-thiouracil (DT)-capped gold nanoparticles (AuNPs). With the presence of uric acid, DT-capped AuNPs rapidly aggregated, and a visible color/photothermal change was used for uric acid quantification within 15 min. The limit of detection was determined to be 11.3 and 6.6 µM for the dual-mode biosensor, leveraging the unique structure of DT to optimize reaction kinetics. Moreover, the sensor exhibited excellent anti-interference capabilities and demonstrated potential for detecting a wide range of uric acid concentrations in complex samples, thereby reducing the need for extensive sample dilution and complex material synthesis procedures. Furthermore, validation against gold standard testing indicates that this biosensor could serve as a highly sensitive assay for quantifying uric acid levels in point-of-care applications, particularly in resource-limited settings.

Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis.

The prevalence of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.

Bright Nanocomposites based on Quantum Dot-Initiated Photocatalysis.

Integrating quantum dots (QDs) into polymer matrix to form nanocomposites without compromising the QD photoluminescence (PL) is crucial to emerging QD light-emitting and solar energy conversion fields. However, the most widely-used bulk polymerization technique, where monomers serve as the QD solvent, usually leads to QD PL quenching caused by radical initiators. Here we demonstrate high-brightness nanocomposites with near-unity PL quantum yield (QY), through a novel QDs-catalyzed (-initiated) bulk polymerization without using any radical initiators. Different from previous reports where QDs were designed as photo-sensitizers/catalysts (always with cocatalysts) and hence non-emissive in catalytic conditions, our QDs combine high brightness with highly effective catalysis, a combination that was previously considered to be hardly possible. In our case, apart from emitting light (at a large probability), the photoexcited QDs act as 'overall reaction' catalysts by simultaneously employing photoexcited electrons and holes to produce active radicals without the need of any sacrificial agents. These active radicals, though with a small amount, are sufficient to initiate effective chain reaction-dominated bulk polymerization, eliminating the requirement of extra radical initiators. This study provides new insights for understanding and development of QDs for energy applications.

Improving the sulfite-detection performance of a fluorescent probe via post-synthetic modification with a metal-organic framework.

In this work, a post-synthetic modification strategy was attempted to improve the performance of the probe for sulfite detection. The assembled platform UiO-66-NH-DQA, which was acquired by anchoring the sulfite-response fluorescent probe DQA onto the surface of UiO-66-NH2via amide covalent bonds, exhibited enhanced fluorescence intensity and practical intracellular imaging capability. In spite of the structural similarity, as verified by characterization tests, the conversion rate of post-synthetic modification was calculated as 35%, equaling an approximate assembly ratio of 1 : 2 between UiO-66-NH2 and DQA. Most significantly, conversion into UiO-66-NH-DQA led to a 5.6-fold enhancement in the reporting signal with a red shift of 20 nm. For sulfite detection, the linear range was 0-150 µM, with a limit of detection value of 0.025 µM. UiO-66-NH-DQA retained advantages including high stability (within pH 5.0-9.0), rapid response (within 15 min) and high selectivity. Based on low cytotoxicity and relatively rapid cellular uptake, UiO-66-NH-DQA achieved the imaging of both the exogenous and endogenous sulfite levels in living cells. In particular, its rapid cell-permeating capability was guaranteed during the modification. The post-synthetic modification strategy reported herein has potential for improving the practical properties of fluorescent monitoring materials.

Single-cell sequencing insights into the transcriptional landscape of Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, with an unknown etiology and no specific treatment. Emerging single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have become instrumental in unravelling cellular heterogeneity and characterizing molecular signatures at single-cell resolution. Single-cell T cell receptor sequencing (scTCR-seq) and single-cell B cell receptor sequencing (scBCR-seq) technologies provide unprecedented opportunities to explore the immune repertoire diversity. These state-of-the-art technologies have been increasingly applied in PD research in the last five years, offering novel insights into the cellular susceptibilities and complex molecular mechanisms underlying PD pathogenesis. Herein we review recent advances in the applications of sc/snRNA-seq, scTCR-seq and scBCR-seq technologies in various PD models. Moreover, we focus on degenerative neurons, activated neuroglial cells, as well as pro-inflammatory immune cells, exploring their unique transcriptional landscapes in PD, as revealed by single-cell sequencing technologies. Finally, we highlight important challenges and the future directions of single-cell experiments in PD research.

Baicalein Ameliorates Insulin Resistance of HFD/STZ Mice Through Activating PI3K/AKT Signal Pathway of Liver and Skeletal Muscle in a GLP-1R-Dependent Manner.

Insulin resistance (IR) is the principal pathophysiological change occurring in diabetes mellitus (DM). Baicalein, a bioactive flavonoid primarily extracted from the medicinal plant Scutellaria baicalensis Georgi, has been shown in our previous research to be a potential natural glucagon-like peptide-1 receptor (GLP-1R) agonist. However, the exact therapeutic effect of baicalein on DM and its underlying mechanisms remain elusive. In this study, we investigated the therapeutic effects of baicalein on diabetes and sought to clarify its underlying molecular mechanisms. Our results demonstrated that baicalein improves hyperglycemic, hyperinsulinemic, and glucometabolic disorders in mice with induced diabetes via GLP-1R. This was confirmed by the finding that baicalein's effects on improving IR were largely diminished in mice with whole-body Glp1r ablation. Complementarily, network pharmacology analysis highlighted the pivotal involvement of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) insulin signaling pathway in the therapeutic actions of baicalein on IR. Our mechanism research significantly confirmed that baicalein mitigates hepatic and muscular IR through the PI3K/AKT signal pathway, both in vitro and in vivo. Furthermore, we demonstrated that baicalein enhances glucose uptake in skeletal muscle cells under IR conditions through the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-adenosine 5'-monophosphate-activated protein kinase (AMPK)-glucose transporter 4 (GLUT4) signaling pathway in a GLP-1R-dependent manner. In conclusion, our findings confirm the therapeutic effects of baicalein on IR and reveal that it improves IR in liver and muscle tissues through the PI3K/AKT insulin signaling pathway in a GLP-1R dependent manner. Moreover, we clarified that baicalein enhances the glucose uptake in skeletal muscle tissue through the Ca2+/CaMKII-AMPK-GLUT4 signal pathway.

Ultrasound elastography: a brief clinical history of an evolving technique.

The history of the emerging elastographic technique is presented. Ultrasound imaging of elasticity and tissue strain has gained clinical acceptance as an established technique useful in routine daily clinical practice.

Automatic tumor segmentation and lymph node metastasis prediction in papillary thyroid carcinoma using ultrasound keyframes.

BACKGROUND: Accurate preoperative prediction of cervical lymph node metastasis (LNM) for papillary thyroid carcinoma (PTC) patients is essential for disease staging and individualized treatment planning, which can improve prognosis and facilitate better management. PURPOSE: To establish a fully automated deep learning-enabled model (FADLM) for automated tumor segmentation and cervical LNM prediction in PTC using ultrasound (US) video keyframes. METHODS: The bicentral study retrospective enrolled 518 PTC patients, who were then randomly divided into the training (Hospital 1, n = 340), internal test (Hospital 1, n = 83), and external test cohorts (Hospital 2, n = 95). The FADLM integrated mask region-based convolutional neural network (Mask R-CNN) for automatic thyroid primary tumor segmentation and ResNet34 with Bayes strategy for cervical LNM diagnosis. A radiomics model (RM) using the same automated segmentation method, a traditional radiomics model (TRM) using manual segmentation, and a clinical-semantic model (CSM) were developed for comparison. The dice similarity coefficient (DSC) was used to evaluate segmentation performance. The prediction performance of the models was validated in terms of discrimination and clinical utility with the area under the receiver operator characteristic curve (AUC), heatmap analysis, and decision curve analysis (DCA). The comparison of the predictive performance among different models was conducted by DeLong test. The performances of two radiologists compared with FADLM and the diagnostic augmentation with FADLM's assistance were analyzed in terms of accuracy, sensitivity and specificity using McNemar's x2 test. The p-value less than 0.05 was defined as a statistically significant difference. The Benjamini-Hochberg procedure was applied for multiple comparisons to deal with Type I error. RESULTS: The FADLM yielded promising segmentation results in training (DSC: 0.88 ± 0.23), internal test (DSC: 0.88 ± 0.23), and external test cohorts (DSC: 0.85 ± 0.24). The AUCs of FADLM for cervical LNM prediction were 0.78 (95% CI: 0.73, 0.83), 0.83 (95% CI: 0.74, 0.92), and 0.83 (95% CI: 0.75, 0.92), respectively. It all significantly outperformed the RM (AUCs: 0.78 vs. 0.72; 0.83 vs. 0.65; 0.83 vs. 0.68, all adjusted p-values < 0.05) and CSM (AUCs: 0.78 vs. 0.71; 0.83 vs. 0.62; 0.83 vs. 0.68, all adjusted p-values < 0.05) across the three cohorts. The RM offered similar performance to that of TRM (AUCs: 0.61 vs. 0.63, adjusted p-value = 0.60) while significantly reducing the segmentation time (3.3 ± 3.8 vs. 14.1 ± 4.2 s, p-value < 0.001). Under the assistance of FADLM, the accuracies of junior and senior radiologists were improved by 18% and 15% (all adjusted p-values < 0.05) and the sensitivities by 25% and 21% (all adjusted p-values < 0.05) in the external test cohort. CONCLUSION: The FADLM with elaborately designed automated strategy using US video keyframes holds good potential to provide an efficient and consistent prediction of cervical LNM in PTC. The FADLM displays superior performance to RM, CSM, and radiologists with promising efficacy.

Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer.

Ovarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum resistance following initial treatment. Despite extensive research on the mechanisms of platinum resistance at the nuclear level, the issue of platinum resistance in ovarian cancer remains largely unresolved. It is noteworthy that mitochondrial DNA (mtDNA) exhibits higher affinity for platinum compared to nuclear DNA (nDNA). Mutations in mtDNA can modulate tumor chemosensitivity through various mechanisms, including DNA damage responses, shifts in energy metabolism, maintenance of Reactive Oxygen Species (ROS) homeostasis, and alterations in mitochondrial dynamics. Concurrently, retrograde signals produced by mtDNA mutations and their subsequent cascades establish communication with the nucleus, leading to the reorganization of the nuclear transcriptome and governing the transcription of genes and signaling pathways associated with chemoresistance. Furthermore, mitochondrial translocation among cells emerges as a crucial factor influencing the effectiveness of chemotherapy in ovarian cancer. This review aims to explore the role and mechanism of mitochondria in platinum resistance, with a specific focus on mtDNA mutations and the resulting metabolic reprogramming, ROS regulation, changes in mitochondrial dynamics, mitochondria-nucleus communication, and mitochondrial transfer.

A Visual Distance-Based Capillary Immunoassay Using Biomimetic Polymer Nanoparticles for Highly Sensitive and Specific C-Reactive Protein Quantification.

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.

Catalytic Asymmetric Hydrogen Atom Transfer Based on a Chiral Hydrogen Atom Donor Generated from TBADT and Chiral BINOL.

Enantioselective radical reactions mediated by TBADT have seldom been seen due to the inherent challenges. Herein, we disclose a new chiral hydrogen atom transfer (HAT) reagent that was generated easily from 8H-BINOL, potassium carbonate, and TBADT under irradiation. The new complex 8H-BINOL/DTs could be used as a chiral H donor. A series of azaarenes could be converted into the corresponding chiral compounds via radical addition followed by enantioselective HAT.

Astaxanthin attenuates glucose-induced liver injury in largemouth bass: role of p38MAPK and PI3K/Akt signaling pathways.

BACKGROUND: Astaxanthin (ASX) has been documented to exert beneficial influence on various processes in fish. Largemouth bass (Micropterus salmoides) serves as a common model for studying glucose-induced liver disease, making it imperative to investigate the regulatory mechanisms underlying its liver health. METHODS: Largemouth bass were fed with a control diet (CON), a high carbohydrate diet (HC), or a HC diet supplemented astaxanthin (HCA) for 8-weeks, followed by the glucose tolerance test (GTT). Primary hepatocytes were treated with low glucose and high glucose combined with different concentrations of astaxanthin for 48 h. The histopathology, enzymology, transcriptomics, molecular biology and cell biology were combined to investigate the mechanism of liver injury. RESULTS: This study provides evidence for the protective effects of ASX against growth performance reduction and hepatic liver injure in largemouth bass fed HC diet. In GTT, HCA diet exhibited an improvement in glucose tolerance following glucose loading. Although HCA diet did not restore the expression of insulin resistance-related genes in livers at different time during the GTT, the addition of ASX in the long-term HC diet did improve the insulin resistance pathway by regulating the PTP1B/PI3K/Akt signaling pathway. Hepatic transcriptome analyses showed that ASX plays an essential role in the modulation of glucose homeostasis in response to treated with HC diet. In in vitro study, ASX treatment resulted in an exaltation in cell viability and a reduction in the rate of cell apoptosis and reactive oxygen species (ROS). Additionally, astaxanthin was observed to improve apoptosis induced by high-glucose via p38MAPK/bcl-2/caspase-3 signaling pathway. CONCLUSIONS: Astaxanthin exhibited a protective effect against apoptosis by regulating p38MAPK/bcl-2/caspase-3 pathway, and ameliorated insulin resistance by activating the PTP1B/PI3K/Akt pathway. This study elucidated the mechanism of astaxanthin in the liver injury of largemouth bass from a new perspective and provided a new target for the treatment of insulin resistance.

Weyl semimetal/dielectric/Weyl semimetal stack for highly circularly polarized thermal radiation.

Highly circularly polarized (CP) infrared thermal radiation is greatly in demand because of its significant potential in mid-infrared (mid-IR) applications. To exploit the magnitude and quality factor of circular dichroism (CD) simultaneously, a lithography-free platform consisting of a Weyl semimetal (WSM)/dielectric (Ge)/WSM stack sitting on a metallic substrate (Mo) is proposed. A chiral response and varying CD values from -1 to 0.957 have been demonstrated. The numerical results from a generalized 4 × 4 transfer matrix algorithm verify that the chiral structure manifests a remarkably high quality factor (Q-factor) of 605. The effect of the thickness of each layer in the stack on the CD value is investigated. Moreover, it is identified that the design results in an angle-independent performance. A dual-channel chiral absorber operating in the 18-21 µm wavelength range has also been achieved. Our simple yet powerful paradigm could offer a new way of manipulating the Q-factor and resonance wavelength of a chiral absorber while maintaining near-unity CD, offering a new approach for the advancement of more efficient and tunable chiral optical devices. The approach is generally applicable to other planar configurations with different WSMs and can be extended to other wavelengths.

The value of the systemic immune-inflammation index in assessing disease severity in autoimmune encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE. METHODS: Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity. RESULTS: This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis. CONCLUSIONS: Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course.

[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

[Pharmacovigilance guidelines of Chinese patent medicines].

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.