OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy， and ensure the safety of drug use in patients. METHODS SWOT （strength， weakness， opportunity， threat） analysis method was used to analyze the internal strengths and weaknesses， as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital， and propose improvement strategies. RESULTS & CONCLUSIONS A refined， full-process， closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established， which is traceable in origin， trackable in destination， and accountable in responsibility. After the application of this system， the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020， the inventory volume decreased by 29.50% compared to the first quarter of 2020， the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020； the average workload per post in the same period of 2023 increased by 49.09% compared to 2019， the dispensing accuracy rate reached 100%， and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

The emergence of teeth is a complex physiological process characterized by the formation of the tooth crown, its movement towards the occlusal plane, and subsequent penetration through the alveolar bone and oral mucosa to achieve functional positioning for contact with opposing teeth. Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are critical regulators of calcium and phosphorus metabolism in the body, playing significant roles in tooth emergence. Their regulatory functions exhibit intricate temporal and spatial dynamics, with underlying mechanisms that remain incompletely understood. In recent years, an increasing number of researchers both domestically and internationally have investigated the role and mechanisms of PTH/PTHrP in tooth emergence, primarily focusing on aspects such as dental sac formation, basal alveolar bone development, coronal alveolar bone resorption, root formation, and periodontal ligament development. Literature reviews indicate that PTH and PTHrP regulate bone metabolism, coordinate various signaling pathways including OPG/RANK/RANKL, cAMP/PKA, and Wnt/β-catenin, and are allosterically modulated by Ca2+ and ATP. These processes contribute to the development of dental sacs, which transmit signals to recruit osteoclasts and promote the resorption of crown alveolar bone, thereby forming an eruption pathway. Additionally, PTH/PTHrP plays a role in the formation of basal alveolar bone, root development, and the periodontal ligament, generating the force necessary for tooth eruption. Through precise spatiotemporal regulation and coordinated efforts, alveolar bone remodeling is achieved, facilitating the intricate process of tooth eruption. Through stringent temporal regulation and multi-faceted cooperation, remodeling of the alveolar bone occurs to complete this intricate developmental process of tooth emergence. Future research should further elucidate the mechanisms underlying PTH/PTHrP actions while also considering optimal dosage regimens regarding timing and frequency for therapeutic applications.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.

Objective:To study the quality and stability of commercial ready-to-use tryptone soya agar(TSA)after storing at 2-25 ℃ for different storage duration under dark condition in order to discuss a determination method of validity period for medium.Methods:Three consecutive batches of ready-to-use TSA medium from two manufac-turers were selected and stored at 2-25 ℃ under dark conditions for 30,90 and 180 days,respectively.The appearance,pH,medium suitability and sterility of the medium were tested.Results:The results of appearance,pH,suitability and sterility of TSA medium from two manufacturers for each batch under different storage duration all met the requirements of the Chinese Pharmacopoeia 2020 Volume IV on the quality control of medium.Conclusion:The TSA medium from two manufacturers all met the requirements when stored for 180 days at 2-25 ℃ under dark condition,indicating that the validity period of TSA medium from two manufacturers can reach 180 days.

In order to investigate the regulatory effect of Codonopsis saponins on the immunosup-pression caused by H9N2 subtype avian influenza virus(AIV)infection,rat pulmonary microvas-cular endothelial cells(RPMECs)were incubated with different concentrations of Codonopsis sap-onins(5,10 and 20 mg/L).The expression level of PD-L1 was detected by RT-PCR and flow cy-tometry,and the contents of TNF-α,IFN-y and IL-10 in supernatant were detected by ELISA kit.The titer of H9N2 AIV in supernatant was detected by plaque method.Then,a co-culture system of RPMECs and T cells was established using a Transwell plate with an aperture of 8 μm to mimic the migration of circulating T cells across microvessels to the site of viral infection.RPMECs were cultured in the upper chamber of Transwell,inoculated with H9N2 AIV,supplemented with 20 mg/L Codonopsis saponins 1 h later,and T cells 36 h later.After 8 h of treatment,T cells in the lower compartment were collected and the proportions of CD4+T cells and CD8+T cells were detected by flow cytometry,the expression levels of IL-2,IFN-y and granzyme B in the superna-tant were detected by ELISA,and the proportions of perforin-1 positive T cells were detected by flow cytometry.The proliferation activity of T cells was detected with the MTT cell proliferation and cytotoxicity assay kit,and the percentage of apoptotic cells was detected by flow cytometry af-ter staining of T cells with Annexin V-FITC/PI.The experimental results showed that Codonopsis saponins could significantly reduce the expression level of PD-L1,IL-10 and TNF-α in RPMECs in-duced by H9N2 AIV infection,and reduce the apoptosis rate of T cells.However,the expression levels of IL-2,IFN-y,perforin-1 and granzyme B in transendothelial migration T cells and the pro-liferation activity of T cells were significantly increased.In this study,Codonopsis saponins can sig-nificantly inhibit the expression of H9N2 AIV-induced PD-L1 in RPMECs,enhance the antiviral function of T cells migrating across the endothelial layer,and enhance the resistance of host to H9N2 AIV.

Objective:To observe the clinical efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)in the treatment of adult acute myeloid leukemia(AML)patients who are unfit for intensive chemotherapy.Methods:The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected,and the efficacy and safety were analyzed retrospectively.Results:After one course of treatment with VEN and AZA,16 out of 21 unfit AML patients reached complete remission(CR)/CR with incomplete hematologic recovery(CRi),2 patients reached partial remission(PR),the overall response rate(ORR)was 85.7％.Among the 16 patients with CR/CRi,13 achieved minimal residual disease(MRD)negativity.Among the 11 patients with adverse prognosis,8 achieved CR/CRi.By the deadline of follow-up,the median overall suivival(OS)of the entire cohort was not reached,with 1-year OS rate of 61.7％.The main adverse events of VEN combined with AZA were myelosuppression,gastrointestinal reactions and infections.There were 13 cases of leukopenia,7 cases of neutropenia,7 cases of anemia,4 cases of thrombocytopenia,and these hematologic adverse events were all grade 3-4.There were 11 cases with gastrointestinal reactions and 7 cases with infections.The above adverse events were controllable and tolerable.No tumor lysis syndrome or infection related death occurred.Conclusion:VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML,and it shows a good safety profile.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P＞0.05)or intraoperative blood loss(200 ml vs 150 ml,P＞0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P＜0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P＜0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0％[9/15]vs 64.0％[16/25],P＞0.05)or at 1 month(80.0％[12/15])vs(76.0％[19/25],P＞0.05),3 months(93.3％[14/15])vs(92.0％[23/25],P＞0.05)and 6 months postoperatively(100％[15/15])vs(96％[24/25],P＞0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.

Objective:To explore the current status of lipid-lowering therapy, the distribution of low-density lipoprotein cholesterol (LDL-C) levels and the risk assessment of cardiovascular events recurrence in patients with coronary heart disease (CHD) complicated by hypertension.Methods:This was a cross-sectional study. Patients with CHD combined with hypertension were hospitalized in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from August 5, 2008 to July 22, 2018 were included, and were divided into standard group and substandard group according to whether LDL-C reached the standard. Study data were obtained from inpatient coronary angiography records and electronic medical records database of Department of Cardiology, General Hospital of Chinese People′s Liberation Army, who used data from the first diagnosis of CHD. Clinical data of the selected patients were collected. Multivariate logistic regression model was used to analyze the associated factors of whether LDL-C reached the standard in CHD patients with hypertension.Results:A total of 18 800 patients were selected from 31 provinces/autonomous regions/municipalities directly under the central government in China, with Beijing accounting for the largest proportion (5 692 patients (30.28%)), followed by Hebei (3 621 patients (19.26%)), Henan (1 837 patients (9.77%)), and Shandong (1 618 patients (8.61%)). Among the selected patients, 1 493 had LDL-C<1.4 mmol/L (standard group), and 17 307 had LDL-C&ge;1.4 mmol/L (substandard group). Only 1 493 patients (7.94%) had LDL-C<1.4 mmol/L. There were 4 518 patients (24.03%), 4 366 patients (23.22%), 6 924 patients (36.83%) and 1 499 patients (7.97%) with LDL-C for 1.4-<2.0, 2.0-<2.5, 2.5-<3.8 and&ge;3.8 mmol/L levels, respectively. 17 855 patients (95.15%) were treated with statins, but only 1 334 patients (7.10%) were treated with statins and ezetimibe. Of the selected patients, 4 986 patients (26.52%) were at low risk, 6 515 patients (34.65%) were at intermediate risk, and 7 299 patients (38.82%) were at high risk. The combined lipid-lowering treatment rates of statin and ezetimibe in the middle-and high-risk patients were 7.43% (484/6 515) and 7.48% (546/7 299), respectively. The results of multivariate logistic regression analysis showed that increasing age, male, diabetes mellitus, stroke, and history of percutaneous coronary intervention (PCI) were positively associated with LDL-C standards in patients with CHD and hypertension, whereas obesity and acute myocardial infarction (AMI) were negatively associated with LDL-C standards (all P<0.01). Conclusions:The rate of achieving the standard LDL-C in patients with CHD combined with hypertension was low in China. Although the majority of patients had received moderate-intensity statin therapy, the proportion of statin-treated patients combined with ezetimibe was extremely low. The proportion of high-risk patients with recurrent cardiovascular events was higher in patients with CHD and hypertension in China, whereas the proportion of such patients receiving statin combined with ezetimibe lipid-lowering therapy was lower. This study also found that increasing age, male, diabetes mellitus, stroke, and history of PCI were positively associated with LDL-C standards, while obesity and AMI were negatively associated with LDL-C standards in patients with CHD and hypertension.