1.Icariin pretreatment enhances effect of human periodontal stem cells on M1-type macrophages
Ting YU ; Dongmei LYU ; Hao DENG ; Tao SUN ; Qian CHENG
Chinese Journal of Tissue Engineering Research 2025;29(7):1328-1335
BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.
2.Effect of Biyan Jiedu Capsules on proliferation and apoptosis of nasopharyngeal carcinoma cells based on PI3K/Akt pathway.
Ting LIN ; Yang-Yang TAO ; Ying-Gang TANG ; Ju YUAN ; Hui-Ping DU ; Lin-Yu DENG ; Fang-Liang ZHOU ; Ying-Chun HE
China Journal of Chinese Materia Medica 2025;50(7):1920-1927
To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans
;
Apoptosis/drug effects*
;
Cell Proliferation/drug effects*
;
Nasopharyngeal Carcinoma
;
Nasopharyngeal Neoplasms/physiopathology*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Cell Line, Tumor
;
Drugs, Chinese Herbal/pharmacology*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Signal Transduction/drug effects*
;
Capsules
;
Carcinoma/drug therapy*
3.Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury.
Jiang-Tao WANG ; Chun-Bao LI ; Jia-Ting ZHANG ; Ming-Yang AN ; Gang ZHAO ; Yu-Jie LIU
Chinese Journal of Traumatology 2025;28(3):187-192
PURPOSE:
The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair.
METHODS:
Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference.
RESULTS:
AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively).
CONCLUSION
In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals
;
Rats, Sprague-Dawley
;
Rotator Cuff Injuries/surgery*
;
Amnion/transplantation*
;
Rats
;
Wound Healing
;
Rotator Cuff/surgery*
;
Male
;
X-Ray Microtomography
;
Tendons/surgery*
;
Biomechanical Phenomena
4.Corrigendum to "Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury" Chinese J Traumatol 28 (2025) 187-192.
Jiang-Tao WANG ; Chun-Bao LI ; Jia-Ting ZHANG ; Ming-Yang AN ; Gang ZHAO ; Yu-Jie LIU
Chinese Journal of Traumatology 2025;28(6):518-518
5.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
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*
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Humans
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Organ Transplantation
;
Immunosuppressive Agents/administration & dosage*
;
Delphi Technique
6.Dorsal CA1 NECTIN3 Reduction Mediates Early-Life Stress-Induced Object Recognition Memory Deficits in Adolescent Female Mice.
Yu-Nu MA ; Chen-Chen ZHANG ; Ya-Xin SUN ; Xiao LIU ; Xue-Xin LI ; Han WANG ; Ting WANG ; Xiao-Dong WANG ; Yun-Ai SU ; Ji-Tao LI ; Tian-Mei SI
Neuroscience Bulletin 2025;41(2):243-260
Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals
;
Female
;
Mice
;
CA1 Region, Hippocampal/metabolism*
;
Cell Adhesion Molecules/metabolism*
;
CRF Receptor, Type 1/metabolism*
;
Memory Disorders/etiology*
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Mice, Inbred C57BL
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Nectins/genetics*
;
Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors*
;
Recognition, Psychology/physiology*
;
Stress, Psychological/complications*
7.Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly.
Ya-Ting AI ; Shi ZHOU ; Ming WANG ; Tao-Yun ZHENG ; Hui HU ; Yun-Cui WANG ; Yu-Can LI ; Xiao-Tong WANG ; Peng-Jun ZHOU
Journal of Integrative Medicine 2025;23(4):390-397
OBJECTIVE:
As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS).
METHODS:
This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA).
RESULTS:
The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS.
CONCLUSION
The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans
;
Cognitive Dysfunction/diagnosis*
;
Aged
;
Male
;
Female
;
Machine Learning
;
Spleen
;
Aged, 80 and over
;
Kidney
;
Medicine, Chinese Traditional
8.Longitudinal Associations between Vitamin D Status and Systemic Inflammation Markers among Early Adolescents.
Ting TANG ; Xin Hui WANG ; Xue WEN ; Min LI ; Meng Yuan YUAN ; Yong Han LI ; Xiao Qin ZHONG ; Fang Biao TAO ; Pu Yu SU ; Xi Hua YU ; Geng Fu WANG
Biomedical and Environmental Sciences 2025;38(1):94-99
9.Analysis of inorganic elements in different batches of earthworm polypeptides by ICP-MS combined with chemometrics technology
Hong-liu YANG ; Wei-ting ZHONG ; Yu-shi GUO ; Shu-qi LI ; Jin-chai QI ; Yong-gang LIU ; Tao MA
Acta Pharmaceutica Sinica 2024;59(4):1040-1047
To establish a method for determining 26 inorganic elements in earthworm polypeptide and determine the elemental content in different batches of earthworm polypeptide, microwave digestion method was used to pre-treat the samples, and ICP-MS method was used to determine the content of 26 elements in different batches of earthworm polypeptide. The linear relationships of 26 elements were good in the range of 0-1 000 μg·L-1, with
10.Study on Evidence-Based Decision-Making of Acupuncture for Post-Prostatectomy Urinary Incontinence: based on TOPSIS Combined with Entropy Method
Zhiwei DONG ; Junlan WANG ; Tao XIE ; Yanying YE ; Ting LI ; Cong YU ; Ning TIAN
Journal of Traditional Chinese Medicine 2024;65(23):2434-2441
ObjectiveTo screen optimized protocol of acupuncture for post-prostatectomy urinary incontinence (PPUI) patients, and to provide evidence for clinical practice. MethodsMEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, WanFang and VIP databases were searched to collect randomized controlled trials of acupuncture for PPUI. The search was conducted from the establishment of the database to February 1, 2024, and the quality of the literature was evaluated to exclude the studies with a high risk of overall bias or modified Jadad <3, and constructed acupuncture protocol and performed meta-analysis. We used International Consultation on Urinary Incontinence Short Form (ICI-Q-SF) scores, quality of life scores, overall effective rate, and modified Jadad scores as beneficial indicators, and the number of acupoints selected, stimulation duration, the number of acupuncture, and the duration of the treatment course as costly indicators, to derive the standardized protocol matrix, and used the entropy method to determine the weights of the different decision-making indicators, and finally combined with the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation. ResultsNine studies met the criteria, and the acupuncture treatments involved were constructed as six protocols including electrical acupoint stimulation with low-frequency, electroacupuncture at four acupoints of sacral region, replenishing qi and tonifying kidney acupuncture, body acupuncture plus pelvic floor muscle training, auricular acupuncture, and electroacupuncture plus pelvic floor muscle training. The ICI-Q-SF, number of acupuncture sessions, and total effectiveness rate were given higher weights in the decision-making indexes, while the stimulation duration and the duration of treatment course were given lower weights; the entropy method of TOPSIS was used for the evaluation and proved that the best protocol was the electroacupuncture at four acupoints of sacral region which used continuous-wave electroacupuncture with a frequency of 2 Hz for 60 min each time, and required the needle sensation to radiate to the root of the penis, with the advantages of streamlined selection of acupoints, a significant reduction in ICI-Q-SF, and an increase in the effectiveness rate. ConclusionThe final optimized protocol was electroacupuncture at four acupoints of sacral region, which can provide an evidence-based basis for clinical decision-making and guideline development.

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