1.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
2.Stimulation mechanism of osteoblast proliferation and differentiation by Duzhong Decoction-containing serum through L-VGCCs.
Ze-Bin CHEN ; Lan-Lan LUO ; Xin-Yi SHI ; Rui-Tong ZHAO ; Cai-Xian HU ; Yun-Ying FU ; Su-Zhen CHAO ; Bo LIU
China Journal of Chinese Materia Medica 2025;50(12):3335-3345
This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals
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Osteoblasts/metabolism*
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Cell Proliferation/drug effects*
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Cell Differentiation/drug effects*
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Mice
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Drugs, Chinese Herbal/pharmacology*
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Calcium Channels, L-Type/genetics*
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Alkaline Phosphatase/genetics*
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Serum/chemistry*
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Cell Line
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Osteogenesis/drug effects*
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Bone Morphogenetic Protein 2/genetics*
3.Impacts of delivery techniques,treatment sites and dose-volume algorithms on results of three-dimensional dosimetric verification for intensity-modulated radiation therapy plans
Xian-Cheng PENG ; Yan-Ming LIU ; Wen-Li LU ; Han-Yin ZHANG ; Ying LI ; Xin YI
Chinese Medical Equipment Journal 2024;45(11):54-59
Objective To investigate the influence of different delivery techniques,treatment sites and dose-volume algorithms on the results of three-dimensional dosimetric verification for intensity-modulated radiation therapy(IMRT)plans and the importance of individualized quality assurance(QA)evaluation standard for radiotherapy plans.Methods Totally 350 tumor patients receiving radiotherapy at some hospital from January 2017 to February 2022 had their three-dimensional dosimetric verification results of IMRT plans selected retrospectively and underwent data collection with COMPASS system,and then were grouped in terms of delivery technique(fixed-beam IMRT and volumetric modulated arc therapy),treatment site(neck,chest and abdomen)and dose-volume algorithm(anisotropic analytical algorithm and collapsed cone convolution algorithm).All the groups were compared based on the 3%/2 mm criterion with regard to the Gamma pass rate of 10%prescription dose area(GP10%),Gamma pass rate(GP50%)and mean Gamma index(μGI5o%)of 50%prescription dose area,dose of 95%target volume(D95%)and its mean dose(Dmean),parotid gland mean dose(Dmean),dose of 1%spinal cord volume(D1%),dose of 1%brain stem volume(D1%)of head and neck radiotherapy plan,heart and lung mean dose(Dmean)and dose of 1%spinal cord volume(D1%)of chest radiotherapy plan and bladder,rectum and femur mean dose of abdomen radiotherapy plan(Dmean).SPSS 26.0 software was used for statistical analysis.Results For different delivery techniques,significant differences were found in all the QA results except GP50%of abdomen radiotherapy plan(P<0.05).For different treatment sites,the differences were statistically significant between the QA results of head and neck radiotherapy plan and abdomen plan and between those of chest radio-therapy plan and abdomen radiotherapy plan(P<0.05),while were not significant between the QA results of head and neck radiotherapy plan and chest radiotherapy plan(P>0.05).For different dose-volume algorithms,the QA results had significant differences except D5%of abdomen radiotherapy planning target volume and Dmean and D1%of chest radiotherapy PTV(P<0.05).Conclusion Dosimetric verification results vary depending on the delivery technique,treatment site and dose-volume algorithm.Statistical process control recommended by AAPM TG-218 report may be involved in to establish individualized QA standard for radiotherapy plans in case universal action limits are not appropriate.[Chinese Medical Equipment Journal,2024,45(11):54-59]
4.Research status of self-disclosure in gynecological cancer patients
Xin LI ; Qingzhao XIAN ; Sisi CHEN ; Ying WANG ; Hongyan SUN ; Xiaoping LEI
Chinese Journal of Practical Nursing 2024;40(18):1431-1436
Based on the domestic and foreign research on the application of self-disclosure in gynecological cancer patients, the relevant concepts, main modes of self-disclosure, measuring tools, research status and influencing factors of self-disclosure in gynecological cancer patients are reviewed. In order to provide a reference for the research on self-disclosure of gynecological cancer population, and promote the development of self-disclosure.
5.Recent Progress in Detection Techniques of Thyroglobulin
Yue WU ; Yong-Jie SHAN ; Shou-Ji CAO ; Shi-Qi JI ; Bo-Wen CHEN ; Xian-Ying MENG ; Zhen-Xin WANG
Chinese Journal of Analytical Chemistry 2024;52(9):1234-1243
Thyroglobulin(Tg)is a glycoprotein with large molecular weight,which is synthesized and secreted into the bloodstream by thyroid follicular cells.The concentration level of Tg in blood is one of the important biomarkers for diagnosis of thyroid diseases such as differentiated thyroid cancer(DTC),subacute thyroiditis,etc..Radioimmunoassay(RIA),immunoradiometric assay(IRMA),and immunochemiluminescence assay(ICMA)are the main clinical methods for detecting Tg.Recently,for meeting the requirement of detecting low concentration of Tg in blood after thyroid clearance surgery,researchers have developed various high-performance analysis methods for detecting Tg concentration in blood samples,providing new assays for thyroid disease screening and efficacy evaluation.This review summarized the analysis methods of Tg,especially the new progresses in the biosensors for monitoring low concentration of Tg in blood during the past five years.The current technical challenges of these methods in clinical applications were briefly discussed,which might provide useful information for developing new liquid biopsy methods of DTC.
6.Observation on the Curative Effect of PENG's Tendon-Separating Tuina Therapy Combined with Lateral Needling Technique for Meridian Sinew in the Treatment of Acute Scapulohumeral Periarthritis
Juan-Juan ZHU ; Huan-Ying ZHU ; Xiao-Wen ZHANG ; Yao-Min ZHANG ; Xin-Xian LI ; Lin XIAO ; Xu-Ming PENG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2094-2099
Objective To observe the clinical effect of PENG's tendon-separating tuina therapy combined with lateral needling technique for meridian sinew in the treatment of acute scapulohumeral periarthritis(referred to as frozen shoulder),and to provide therapeutic ideas and evidence for the treatment of acute scapulohumeral periarthritis.Methods Sixty patients with acute scapulohumeral periarthritis were randomly divided into treatment group and control group,with 30 cases in each group.The control group was treated with lateral needling technique for meridian sinew,and the treatment group was treated with PENG's tendon-seperating tuina therapy combined with lateral needling technique for meridian sinew.Both groups were treated for once a day,10 times as a course of treatment,and for a total of 2 courses of treatment.The changes of pain Visual Analogue Scale(VAS)score and Constant-Murley Scale(CMS)score of shoulder joint function in the two groups were observed before treatment and after one and two course(s)of treatment.Moreover,the clinical efficacy of the two groups was evaluated.Results(1)After two courses of treatment,the total effective rate of the treatment group was 90.00%(27/30),and that of the control group was 73.30%(22/30).The overall efficacy(tested by rank sum test)and total effective rate(tested by chi-square test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P<0.05).(2)After one and two course(s)of treatment,the VAS scores of pain in the two groups were significantly decreased than those before treatment(P<0.05 or P<0.01);after two courses of treatment,VAS scores in the two groups were significantly lower than those after one course of treatment(P<0.05).The decrease of VAS scores in the treatment group after one and two course(s)of treatment was significantly superior to that in the control group,and the difference were statistically significant(P<0.05 or P<0.01).(3)After one and two course(s)of treatment,the CMS scores of shoulder joint function in the two groups were significantly higher than those before treatment(P<0.01);after two courses of treatment,the CMS scores in the two groups were higher than those after one course of treatment(P<0.05).The increase of CMS scores in the treatment group after one and two course(s)of treatment was significantly superior to that in the control group,and the difference was statistically significant(P<0.01).Conclusion PENG's tendon-separating tuina therapy combined with lateral needling technique for meridian sinew has a definite clinical effect in the treatment of patients with acute scapulohumeral periarthritis,which can effectively relieve the pain and discomfort of shoulder joint and improve the movement function of shoulder joint.
7.Total saponins from Trillium tschonoskii maxim alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis through Keap-1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways
Jian-Hong GAO ; Tian-Ying SONG ; Chao-Xi TIAN ; Fang-Yu ZHAO ; Yi-Duo HE ; Xin LIU ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(10):1850-1857
Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P<0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P<0.01)and increased MDA levels(P<0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P<0.05,P<0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.
8.Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels
Ying-Xin LI ; Yi-Dan LI ; Pei WANG ; Hui-Jie JIAO ; Ying LI ; Jing ZHANG ; Xian-Hua YUAN
Journal of Experimental Hematology 2024;32(3):733-741
Objective:To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma(PTCL)patients with different levels of histone deacetylase(HDAC)based on latent class analysis.Methods:112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group.The clinical data of the two groups of patients were compared.Multivariate logistic regression was used to analyze the risk factors for recurrence.Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group.Results:There were 87 patients(77.68%)in recurrence group and 25 patients(22.32%)in non-recurrence group.The result of multivariate logistic regression showed that ECOG score ≥2,Ann Arbor stage Ⅲ-Ⅳ,IPI score>2,bone marrow involvement,elevated serum β2-microglobulin(β2-MG),short-term efficacy not reaching complete remission(CR)or partial remission(PR),and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL(P<0.05).The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels(P<0.05).The results of cluster analysis showed that the risk of recurrence was obviously clustered,and the patients could be divided into high recurrence risk group(HDAC>5 points)and low recurrence risk group(HDAC≤5 points).The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group,compared with the low recurrence risk group(P<0.05).Conclusion:There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.
9.A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers.
Xiao Peng YU ; Jia Lu CHEN ; Yue TANG ; Chen CHEN ; Ying Hong QIU ; Hong WU ; Tian Qiang SONG ; Yu HE ; Xian Hai MAO ; Wen Long ZHAI ; Zhang Jun CHENG ; Xiao LIANG ; Jing Dong LI ; Chuan Dong SUN ; Kai MA ; Rui Xin LIN ; Zhi Min GENG ; Zhao Hui TANG ; Zhi Wei QUAN
Chinese Journal of Surgery 2023;61(4):321-329
Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.
10.Association Between Dietary Knowledge and Food Preferences in Residents Aged 18 and Over in China Based on Latent Class Analysis.
Zhen-Xin MA ; Wei-Ye CHEN ; Yu-Xian KUANG ; Yi-Ying ZHENG ; Ke-Yuan LU ; Gao-Yong ZOU ; Ding ZENG ; Li LIU
Acta Academiae Medicinae Sinicae 2023;45(5):730-736
Objective To investigate the food preferences and explore the potential association between dietary knowledge and food preferences in residents aged 18 and over in China,so as to provide a basis for promoting healthy diets.Methods The latent class analysis was carried out with the 2015 cross-sectional data of China health and nutrition survey to categorize the food preferences among 8 783 residents aged 18 and over.Multinomial Logistic regression was adopted to assess the association between and dietary knowledge and food preferences.Results The food preferences of the residents aged 18 and over in China were classified into preference for less vegetable(3.28%),lack of preference(11.20%),diverse preferences(4.19%),and preference for healthy diets(81.33%).The proportion of the adults with dietary knowledge was 36.87%(3 238/8 783).The dietary knowledge varied in the adults with different food preferences(all P<0.001).After adjusting for gender,age,urban and rural distribution,education background,and annual household income,for each point increase in the dietary knowledge score,there was an estimated reduction of 22% in the probability of preferring less vegetables(OR=0.78,95%CI=0.76-0.80, P<0.001),13% in the probability of lacking preference(OR=0.87,95%CI=0.86-0.89, P<0.001),and 3% in the probability of having diverse preferences(OR=0.97,95%CI=0.94-1.00, P=0.030).Compared with those lacking dietary knowledge,the individuals with dietary knowledge had a 77% less probability of preferring less vegetables(OR=0.23,95%CI=0.16-0.32, P<0.001),a 55% less probability of lacking preference(OR=0.45,95%CI=0.39-0.53, P<0.001),and a 23% less probability of having diverse preferences(OR=0.77,95%CI=0.61-0.96, P=0.023).Conclusions The residents aged 18 and over in China presented four food preferences,including preference for less vegetables,lack of preference,diverse preferences,and preference for healthy diets,the last of which had the highest proportion.The individuals with lower levels of dietary knowledge have higher probability of preferring unhealthy food.
Adult
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Humans
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Adolescent
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Food Preferences
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Latent Class Analysis
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Cross-Sectional Studies
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Diet
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Nutrition Surveys
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China

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