OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

Objective To investigate the role and related mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in radiation-induced lung injury (RILI). Methods Human umbilical cord-derived MSCs were isolated and cultured for the extraction and identification of exosomes. Eighteen male SD rats were randomly divided into Control group, RILI group and RILI + exosomes group (EXO group), with 6 rats in each group. Except for Control group, the other groups received a single X-ray dose of 30 Gy to the right lung. Immediately after irradiation, the EXO group was administered 2 × 10⁹ exosomes/kg via tail vein injection. Control group and RILI group were given the same volume of normal saline. Eight weeks post-irradiation, the rats were sacrificed, lung tissue and peripheral venous blood were collected. HE and Masson staining were employed to observe the pathological and fibrotic changes of lung tissue. The levels of serum inflammatory factors IL-6, IFN-γ, TNF-α, and IL-10 were detected by ELISA. RT-qPCR was used to assess the mRNA levels of IL-1β, IL-6, Cdh1, and Col1a1 in lung tissue. The expression levels of Vimentin and TGF-β1 in lung tissue were measured by immunohistochemical staining. The expression levels of AMPK, p-AMPK, and TGF-β1 in lung tissue were detected by Western blot. Results MSC-derived exosomes were successfully extracted and identified. Compared with RILI group, EXO group showed significantly reduced pathological changes of lung inflammation and collagen deposition. The levels of serum inflammatory factors IL-6, INF-γ, and TNF-α were significantly decreased (P < 0.05), and the level of anti-inflammatory factor IL-10 was significantly increased (P < 0.05). The mRNA levels of IL-1β, IL-6, and Col1a1 in lung tissue were significantly decreased (P < 0.05 or P < 0.01), and the mRNA level of Cdh1 was significantly increased (P < 0.05 or P < 0.01). The levels of Vimentin and TGF-β1 in lung tissue were significantly reduced, while p-AMPK level was significantly up-regulated (P < 0.05). Conclusion Exosomes derived from MSCs may alleviate RILI by inhibiting inflammatory responses and regulating epithelial-mesenchymal transition mediated by AMPK/TGF-β1 signaling pathway.

OBJECTIVE To investigate the effects of parthenolide （PLT） on systemic inflammation and intestinal injury in rats with acute pancreatitis （AP） by regulating the Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor-erythroid-2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution （1 mL/kg） into the biliary pancreatic duct， and modeled rats were divided into AP group， PLT （300 µg/kg） group， dexamethasone （2 mg/kg） group， inhibitor （11 mg/kg Nrf2 inhibitor ML385） group， and PLT+inhibitor group （300 µg/kg PLT+11 mg/kg ML385）， with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h， serum lipase and amylase levels， the levels of oxidative stress index [superoxide dismutase （SOD） and malondialdehyde （MDA）] and inflammatory factors [interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α）] were detected. The histopathological changes in colon mucosa and pancreas were observed， and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1， Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group， there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue， cell shedding or tissue necrosis and severe bleeding； serum levels of lipase， amylase， MDA， IL-1β， IL-6 and TNF-α， Chiu and Schmidt scores， apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated， while SOD level and protein expressions of Nrf2 20230993） and HO-1 were decreased or down-regulated significantly （P＜0.05）. Compared with the AP group， the above indexes in the PLT group and dexamethasone group were significantly improved， while those in the inhibitor group further deteriorated （P＜0.05）. Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats （P＜ 0.05）. CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats， alleviates intestinal damage， and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.

ObjectiveWith the development of society and the increasing demand for pregnancy at an advanced age， diminished ovarian reserve （DOR） has attracted wider attention. This disease affects the normal menstruation of women and poses a threat to their mental health. Current research on DOR is still in the initial stage， and advancing research progress in DOR necessitates the construction of effective and clinically relevant animal models. Building on existing literature and integrating the diagnosis criteria of DOR in traditional Chinese medicine （TCM） and Western medicine， this study summarized， analyzed， and evaluated existing models， providing a reference for optimizing DOR animal models. MethodsA retrospective analysis of literature on DOR-related animal models was conducted， and the diagnostic criteria of DOR in TCM and Western medicine were sorted out. By means of evaluation methods of animal models， the clinical relevance of each model to TCM and Western medicine was assessed. ResultsDOR animal models included those based on natural factors， iatrogenic factors， immune factors， metabolic factors， and environmental factors. Among them， the model based on iatrogenic factors， especially models induced by Tripterygium wilfordii preparations， cyclophosphamide， and cisplatin， had a high degree of relevance to both Western medical diseases and TCM syndromes and was confirmed as the optimal modeling method for studying DOR at present. ConclusionThe existing DOR modeling methods mostly have a high degree of clinical relevance to Western medical diseases， while the number of DOR animal models with clear TCM syndromes is very limited. TCM plays an indispensable role in exploring DOR treatment methods. Therefore， the development of DOR animal models related to TCM syndromes should be strengthened， further exploring the potential of TCM and providing strong theoretical support for the application of TCM in DOR treatment.

ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

Objective:To explore the clinical manifestations, recurrence factors, and outcomes of revision surgery for recurrent thyroglossal duct cysts and fistulas in children. Methods:A retrospective study was conducted on the clinical manifestations, the relationship between cysts/ fistulas and residual hyoid bone of 10 patients with recurrent thyroglossal cysts and fistulas admitted to our hospital from July 2015 to July 2023, as well as the methods and effects of revision surgery. Results:The recurrence time after the initial surgery was between 7 months and 6 years, with an average of 2 years and 1 month.Clinical manifestations: 50%（5 cases） of patients have recurrent cysts near the incision, 40%（4 cases） had recurrent infections at the incision and eventually form fistulas, and 10%（1 case） experienced sleep snoring and pharyngeal trouble, were diagnosed with lingual thyroglossal duct cyst through laryngoscopy. All cysts or fistulas are connected to residual hyoid bodies, and three cases have intact hyoid bodies.Revision surgery: Nine cases underwent modified Sistrunk surgery, removing cysts, fistulas, and residual hyoid bodies. Suspension laryngoscopy and coblation were employed to treat the lingual thyroglossal duct cyst. After the revision surgery, follow-up was conducted for 8 months to 3 years, and no recurrence was found. Conclusion:All recurrences of thyroglossal duct cysts in this study were associated with residual hyoid bodies. Therefore, for thyroglossal duct cysts or fistulas, whether it is the first surgery or a revision surgery, it is recommended to choose the optimized Sistrunk operation, with the key point being complete resection of the hyoid body. Cases with lingual thyroglossal duct cyst can be treated with suspension laryngoscopy by coblation. Whether to remove the residual hyoid body requires further observation.
Humans ; Thyroglossal Cyst/surgery* ; Retrospective Studies ; Recurrence ; Reoperation ; Fistula/surgery* ; Child ; Hyoid Bone/surgery* ; Male ; Female ; Treatment Outcome ; Laryngoscopy ; Child, Preschool

Objective:To explore the clinical efficacy of the coblation resection of lingual thyroglossal duct cysts under self-retaining laryngoscopy. Methods:A retrospective analysis was conducted on the clinical data of 22 patients with lingual thyroglossal duct cysts admitted to our hospital from December 2016 to December 2023. There were 16 males and 6 females, aged 2 years to 12 years and 3 months（mean: 4 years 1 month; median: 3 years 3 months）. The lingual thyroglossal duct cysts were removed by coblation under self-retaining laryngoscopy. If the cysts could not be removed completely, the epithelial cells of the remaining cysts would be ablated. Results:There were 22 cases of lingual thyroglossal duct cysts，13 cases （59.1%） of lingual thyroglossal duct cysts had laryngeal stridor and dyspnea. The postoperative follow-up period is 3 months to 7 years. 11 cases （50.0%） underwent secondary laryngoscopic evaluation.There were 4 cases of recurrence （18.2%）, with no laryngeal obstruction,bleeding, or nerve damage. Conclusion:Laryngeal stridor and dyspnea are the main clinical symptoms of lingual thyroglossal duct cysts in children. The coblation resection of lingual thyroglossal duct cysts under self-retaining laryngoscopy is safe and effective. Cyst recurrence correlates strongly with residual cyst walls, emphasizing the need for enhanced intraoperative visualization and refined surgical precision.
Humans ; Thyroglossal Cyst/surgery* ; Male ; Female ; Child ; Retrospective Studies ; Child, Preschool ; Laryngoscopy/methods* ; Treatment Outcome ; Catheter Ablation/methods*

OBJECTIVES: This study investigated the effects of a polycaprolactone (PCL)-polyethylene glycol (PEG) scaffold incorporated with concentrated growth factor (CGF) on the adhesion, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). METHODS: The PCL-PEG-CGF composite scaffold was fabricated using an immersion and freeze-drying technique. Its microstructure, mechanical properties, and biocompatibility were systematically characterized. The hPDLSCs were isolated through enzymatic digestion, and the hPDLSCs were identified through flow cytometry. Third-passage hPDLSCs were seeded onto the composite scaffolds, and their adhesion, proliferation and osteogenic differentiation were assessed using CCK-8 assays, 4',6-diamidino-2-phenylindole (DAPI) staining, alkaline phosphatase (ALP) staining, alizarin red staining, and Western blot analysis of osteogenesis-related proteins [Runt-related transcription factor 2 (Runx2), ALP, and morphogenetic protein 2 (BMP2)]. RESULTS: Scanning electron microscopy revealed that the PCL-PEG-CGF composite scaffold exhibited a honeycomb-like structure with heterogeneous pore sizes. The composite scaffold exhibited excellent hydrophilicity, as evidenced by a contact angle (θ) approaching 0° within 6 s. Its elastic modulus was measured at (4.590 0±0.149 3) MPa, with comparable hydrophilicity, fracture tensile strength, and fracture elongation to PCL-PEG scaffold. The hPDLSCs exhibited significantly improved adhesion to the PCL-PEG-CGF composite scaffold compared with the PCL-PEG scaffold (P<0.01). Additionally, cell proliferation was markedly improved in all the experimental groups on days 3, 5, and 7 (P<0.01), and statistically significant differences were found between the PCL-PEG-CGF group and other groups (P<0.01). The PCL-PEG-CGF group showed significantly elevated ALP activity (P<0.05), increased mineralization nodule formation, and upregulated expression of osteogenic-related proteins (Runx2, BMP2 and ALP; P<0.05). CONCLUSIONS The PCL-PEG-CGF composite scaffold exhibited excellent mechanical properties and biocompatibility, enhancing the adhesion and proliferation of hPDLSCs and promoting their osteogenic differentiation by upregulating osteogenic-related proteins.
Humans ; Polyesters/chemistry* ; Periodontal Ligament/cytology* ; Polyethylene Glycols/chemistry* ; Stem Cells/cytology* ; Tissue Scaffolds ; Cell Proliferation ; Osteogenesis ; Cell Differentiation ; Cell Adhesion ; Bone Morphogenetic Protein 2/metabolism* ; Cells, Cultured ; Alkaline Phosphatase/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Intercellular Signaling Peptides and Proteins/pharmacology* ; Tissue Engineering/methods*

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.