ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

BACKGROUND:Liver organoids are of great significance to elucidate the exact pathological mechanism of liver diseases and the treatment of liver diseases. OBJECTIVE:To summarize the basic research in this field at home and abroad,review the important research progress in the construction of liver organoids,disease modeling and transplantation therapy,and discuss the application prospect of combined tissue engineering technology of liver organoids. METHODS:The relevant articles included in PubMed and CNKI databases were searched.The English and Chinese search terms were"liver,organoids,liver diseases."The main search time was from April 2018 to April 2024.Duplicate literature was excluded by manual reading.Finally,94 articles were included for review and analysis. RESULTS AND CONCLUSION:The seed cells constructed by liver organoids are mainly concentrated in adult cells and pluripotent stem cells,which promote the generation of organoids by assisting various cytokines to participate in signal guidance and providing 3D microenvironment by extracellular matrix.However,the overall maturity is not high,which is expected to improve this problem by combining tissue engineering technology.In vitro disease modeling is mainly studied in the field of simple diseases and single-gene genetic diseases.Organoids highly retain patient genetic characteristics,and it is expected to simulate more complex liver diseases and clarify deeper pathological mechanisms by combining CRISPR-Cas9 gene correction and other emerging technologies.In vivo transplantation treatment,liver organoids can be safely and effectively implanted,showing amazing liver function replacement potential,tissue regeneration ability,and may also be combined with other tissue engineering materials to achieve therapeutic purposes.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P<0.05). The serum Vit A(0.34±0.18 μmol/L)and bFGF(0.44±0.18 ng/L)levels in stage 3-5 ROP group were lower than those in the group without ROP(P<0.05). The serum Vit A and bFGF levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(P<0.05). At 35d postnatal, the serum Vit A(0.33±0.19 μmol/L)and bFGF(0.39±0.19 ng/L)levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(0.43±0.16 μmol/L and 0.48±0.17 ng/L; all P<0.05). According to the ROC curve drawn by serum Vit A, the AUC value was 0.853, the maximum Youden index was 0.68, the best sensitivity was 73%, and the best specificity was 95%. According to the ROC curve drawn by serum bFGF, the AUC value was 0.828, the maximum Youden index was 0.58, the best sensitivity was 90%, and the best specificity was 68%. According to the ROC curve drawn by serum Vit A combined with bFGF, the AUC value was 0.917, the maximum Youden index was 0.70, the best sensitivity was 70%, and the best specificity was 100%.CONCLUSION: Serum Vit A and bFGF levels are sensitive and effective indicators for predicting ROP. If the serum Vit A or bFGF levels are lower in premature infants or low birth weight infants, it may indicate the higher probability of ROP and its pathological stages. In addition, the clinica value of serum Vit A combined with bFGF in the diagnosis of ROP is higher than that of Vit A or bFGF alone, and the misdiagnosis rate is reduced.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Huangqin Decoction is a classic formula published in the Catalogue of Ancient Classical Famous Prescriptions(the Sec-ond Batch).This paper systematically collates,researches and analyzes the ancient and modern clinical literature that records Huan-gqin Decoction,sorts out key issues such as the prescription origin,composition,medicine origin,processing method,usage and dos-age,efficacy and indications of Huangqin Decoction,and performs predictive analysis on its quality markers(Q-Marker)to provide lit-erature and theoretical support for the clinical application and preparation development of Huangqin Decoction from the entire process of textual research-preparation development-quality evaluation.After analysis and research,it is found that Huangqin Decoction is de-rived from Zhang Zhongjing's Treatise on Cold Damage.It consists of Scutellaria baicalensis,Radix Paeoniae Alba,and Glycyrrhiza,with Jujube serving as the guiding herb.The medicine origin follows the 2020 edition of the Chinese Pharmacopoeia.Scutellaria ba-icalensis and Radix Paeoniae Alba are taken in the raw form;Glycyrrhiza is lightly fried and Jujubes with sliced pieces.The doasge of medicine is 11.19 of Scutellaria baicalensis,7.46 g of Radix Paeoniae Alba and Glycyrrhiza,and jujubes are added or subtracted ac-cording to the situation.The method of preparation and administration is that all herbs are added with 2 000 mL of water,decocting to 600 mL.The decoction can be consumed warm 3 times a day at any suitable time.The formula was commonly used in ancient times for dysentery,but now it is also used for other digestive system diseases such as ulcerative colitis and chronic colitis,which are mainly characterized by diarrhea.The suggested Q-markers for Huangqin Decoction are baicalin,baicalein,wogonin,paeoniflorin,glycyrrhi-zin and glycyrrhizic acid.

Objective:To analyze the spatial-temporal distribution of etiologically positive pulmonary tuberculosis (PTB) at the county (city, district) unit in Jiangsu Province from 2011 to 2021 to provide evidence for the implementation and adjustment of prevention and control strategies of PTB in Jiangsu Province.Methods:The registration data of etiologically positive PTB patients in Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System in the China Information System of Disease Control and Prevention. Data on the permanent population were from the statistical yearbook of each county (city, district) in Jiangsu Province. Geoda 1.18.0 software was used to analyze the global and local spatial autocorrelation and explore the spatial clustering. SaTScan 10.1 software was used to analyze the spatial-temporal clusters, and ArcGIS 10.7 software was used to visualize the spatial-temporal clusters.Results:A total of 128 240 etiological positive PTB cases were registered in Jiangsu Province from 2011 to 2021, with an average annual registration rate of 13.99/100 000. The registration rate showed an overall upward trend (trend χ2=63.49, P<0.001) after 2017, and the etiologically positive rate showed an overall upward trend (trend χ2=3 710.86, P<0.001). The annual Moran's I values ranged from 0.107 to 0.343, which showed a spatial clustering distribution. The results of local spatial autocorrelation analysis showed that there were "high-high" clustering areas in Jiangsu Province each year, showing a dynamic distribution, and most of the areas were distributed in the central and southern regions of Jiangsu Province, with the largest number (7) in 2015 and the smallest number (1) in 2011. A total of 4 spatial-temporal clustering areas were explored by spatial-temporal scanning analysis (all P<0.001), among which the first-level clustering area covered 3 counties (cities, districts), namely Changshu, Taicang, and Xiangcheng District of Suzhou, and the clustering time was from 2011 to 2015. The secondary clustering areas covered 24 counties (cities, districts), mainly covering Jiangsu's central and northern regions, such as Huai'an, Suqian, and Yancheng. The third-level clustering areas covered 26 counties (cities, districts); the fourth-level clustering area was the Gaochun District of Nanjing, with the clustering period from 2017 to 2021. Conclusions:From 2011 to 2021, the etiologically positive PTB registration rate at the county (city, district) level in Jiangsu Province had obvious spatial-temporal clustering characteristics. The clustering areas included the northern areas with relatively backward economies and the southern areas with better economic development. Multiple measures should be taken to prevent and control PTB according to the specific situation in different regions.