1.Research progresses on the mechanism of macrophages in tendon bone healing.
Liang WANG ; Yinshuan DENG ; Tao QU ; Chaoming DA ; Yunfei HE ; Rui LIU ; Weimin NIU ; Weishun YAN ; Zhen CHEN ; Shuo LI ; Zhiyun YANG ; Binbin GUO ; Xueqian LAI
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):183-187
The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans
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Macrophages/metabolism*
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Wound Healing
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Animals
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Tendons/physiology*
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Bone and Bones/injuries*
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Tendon Injuries
2.Structure of myelin in the central nervous system and another possible driving force for its formation-myelin compaction.
Qi SHAO ; Simin CHEN ; Tian XU ; Yuyu SHI ; Zijin SUN ; Qingguo WANG ; Xueqian WANG ; Fafeng CHENG
Journal of Zhejiang University. Science. B 2025;26(4):303-316
Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism*
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Humans
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Central Nervous System/metabolism*
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Animals
3.A small-molecule anti-cancer drug for long-acting lysosomal damage.
Shulin ZHAO ; Qingjie BAI ; Guimin XUE ; Juan WANG ; Luyao HU ; Xueqian WANG ; Yan LI ; Shuai LU ; Yangang SUN ; Zhiqiang ZHANG ; Yanling MU ; Yanle ZHI ; Qixin CHEN
Acta Pharmaceutica Sinica B 2025;15(11):5867-5879
Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.
4.Liquiritin improves macrophage degradation of engulfed tumour cells by promoting the formation of phagolysosomes via NOX2/gp91phox.
Caiyi YANG ; Kehan CHEN ; Yunliang CHEN ; Xuting XIE ; Pengcheng LI ; Meng ZHAO ; Junjie LIANG ; Xueqian XIE ; Xiaoyun CHEN ; Yanping CAI ; Bo XU ; Qing WANG ; Lian ZHOU ; Xia LUO
Journal of Pharmaceutical Analysis 2025;15(5):101093-101093
The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.
5.Clinical study of electroacupuncture improving sleep electroencephalogram and event-related potential in patients with somatoform disorders
Zhanwen LIU ; Li ZHANG ; Minmin ZHANG ; Xueqian HU ; Xingshi CHEN ; Jie SU ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(1):58-64
Objective:To observe the effects of electroacupuncture(EA)on sleep electroencephalogram(EEG)and event-related potential(ERP)in patients with somatoform disorders(SFD). Methods:Seventy-five SFD patients were recruited as an EA group to receive EA at Shenting(GV24)and Baihui(GV20)once daily,30 min each time,with 6 straight days as a treatment course,and 4 courses were conducted at 1-day intervals.Before treatment,patients underwent a survey using a physical symptom checklist on their primary symptoms.Before and after treatment,their sleep EEG was monitored using Quisi,and the ERP mismatch negativity(MMN)and P300 were detected.The Quisi sleep EEG and ERP were also examined among 40 normal volunteers as the normal group data. Results:During the trial,13 cases were removed from the EA group due to incomplete data,and 62 cases were finally included for statistical analyses.Of the 62 SFD patients,the main disturbing symptoms were cognitive impairments,sleep disorders,respiratory symptoms,digestive symptoms,five-sense organ problems,and cardiovascular symptoms in order.Before treatment,the EA group had increased MMN and P300 latencies and decreased amplitudes compared with the normal control group(P<0.01 or P<0.05);according to Quisi,the EA group also had reduced total sleep time(TST),shorter rapid eye movement sleep(REM)latency(RL)and REM time(RT),smaller number of REM period(NRP),extended sleep latency(SL),longer awaking time(AT),lower sleep efficiency(SE),larger percent of non-rapid eye movement sleep(NREM)stage 1(S1)and smaller percent of NREM stage 2(S2),and the percent of slow wave sleep(SWS),i.e.NREM stage 3(S3)plus stage 4(S4),also went down,all presenting significant differences between groups(P<0.01 or P<0.05).After 4 courses of treatment,the MMN and P300 latencies were reduced,and their amplitudes became larger in the EA group compared with the baseline(P<0.05);they had insignificant differences compared with the normal control group(P>0.05).Quisi showed that the TST and RL increased,and the SL and AT decreased in the EA group,and the predominant change in sleep architecture was reduced S1 percent,increased S2,and improved SE,all showing significant intra-group differences(P<0.01 or P<0.05);however,the intra-group difference in the NRP was statistically insignificant(P>0.05).Except the TST,RT,S1 percent,and SWS,there was no statistical significance in comparing the other Quisi parameters(including RL,NRP,SL,AT,SE,and S2 percent)between the two groups(P>0.05). Conclusion:SFD patients have a variety of clinical symptoms,and most of them show abnormal sleep EEG and ERP;EA can correct abnormal sleep EEG parameters and the MMN and P300 of ERP in SFD patients.
6.Effect of vitamin C on intestinal flora disorders in Cr(VI)-contaminated mice
Limin ZHANG ; Chen LIU ; Yumei LIU ; Xueqian WU ; Ming SHU ; Jian ZHOU ; Dongqun XU ; Qin WANG ; Wanwei LI ; Xiaohong LI
Journal of Environmental and Occupational Medicine 2024;41(7):807-813
Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K2Cr2O7, Cr(VI)], and VC+K2Cr2O7 [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K2Cr2O7 solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K2Cr2O7 solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg−1, and the dose of K2Cr2O7 was 1.25 mg·kg−1. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.
7.Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway
Xueqian XIE ; Pengcheng LI ; Meng ZHAO ; Bo XU ; Guixing ZHANG ; Qing WANG ; Chen NI ; Xia LUO ; Lian ZHOU
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):991-1002
The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2%DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.
8.Exploration on the Chinese Medical Master Wang Qingguo's Medication Law in Treating Insomnia Based on Data Mining
Jiahui CHEN ; Chongyang MA ; Qi SHAO ; Jing JI ; Wenxiu XU ; Fafeng CHENG ; Xueqian WANG ; Qingguo WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):90-95
Objective To explore the medication law of Professor Wang Qingguo for the treatment of insomnia based on data mining technology.Methods Paper-based prescriptions for Professor Wang Qingguo's treatment of insomnia from December 2016 to August 2023 were collected and a database was constructed.The screened prescriptions were subjected to data mining such as frequency statistics,association rule analysis,and clustering analysis.Results Totally 399 effective outpatient prescriptions were screened-out,involving 276 kinds of Chinese materia medica,with a total frequency of 6738 times.There were 38 Chinese materia medica with a frequency of use≥50.The properties were mainly warm,cold and mild,the tastes were mainly sweet,bitter and pungent,and mainly belong to the lung,spleen and heart meridians.Association rule analysis showed that the most commonly used drug combinations were"Fructus Tritici Levis-Scutellariae Radix-Bupleuri Radix","Pericarpium Citri Reticulatae-Scutellariae Radix-Pinelliae Rhizoma",etc.Association rule network analysis obtained a core prescription containing 12 kinds of Chinese materia medica for insomnia.Four new drug combinations were obtained by clustering analysis.Conclusion Professor Wang's treatment of insomnia has the characteristics of following the original meaning of Huang Di Nei Jing and Nan Jing,making good use of the classical prescription,applying combined prescription,flexible use of prescription,combining ancient and modern prescriptions,using specific medicine.It deeply reflects the academic view of"Tongping Zhihe".
9.Diagnostic value of probe-based confocal laser microendoscopy in differential diagnosis of fundic gland polyps
Ziyi WANG ; Jing CHEN ; Xueqian ZHOU ; Jia YANG ; Xiangyong MENG ; Jing WU ; Wensheng CHEN
Journal of Army Medical University 2024;46(10):1150-1157
Objective To explore the value of probe-based confocal laser endomicroscopy(pCLE)in the differential diagnosis of fundic gland polyps.Methods A total of 63 patients who underwent conventional white light image(WLI)and suggested with gastric polyps in our gastroenterology endoscopy center during June and December 2023 were enrolled,and their clinical data,WLI,narrow band images(NBI),pCLE images and postoperative histopathological findings were collected.The characteristics of fundic gland polyps under pCLE were statistically verified,and the sensitivity,specificity,accuracy and consistency of different endoscopic diagnoses were calculated respectively.Results Under pCLE,fundic gland polyps were mainly manifested as elongated gastric pit opening,"hand-in-hand"gastric pit opening,well-arranged blood vessels around the pit opening,and no luciferin oozing.The sensitivity,specificity,accuracy of WLI were 72.73%,75.00%,73.13%and 0.343 for fundic gland polyps,and 81.82%,71.43%,71.64%and 0.354 for hyperplastic polyps,respectively.While,the above values of NBI were 87.27%,83.33%,86.57%and 0.673 for fundic gland polyps,and 81.82%,85.71%,85.07%and 0.554 for hyperplastic polyps;and those of pCLE were 92.73%,91.67%,92.53%and 0.769 for fundic gland polyps,and 90.91%,94.64%,94.03%and 0.797 for hyperplastic polyps pCLE had better sensitivity,specificity and accuracy than WLI and NBI,and had the results consistent with histopathological findings.Conclusion pCLE can be used in the differential diagnosis of fundic gland polyps.
10.Current status and influencing factors of low anterior resection syndrome in rectal cancer patients with sphincter-preserving surgery
Xueqian MA ; Jiaqi XU ; Yanan YANG ; Miao YU ; Hongbo CHEN ; Baohua LI
Chinese Journal of Modern Nursing 2024;30(34):4646-4653
Objective:To explore the incidence of low anterior resection syndrome (LARS) in patients undergoing sphincter-preserving surgery for rectal cancer and analyze related factors.Methods:This study was a cross-sectional survey. From 2021 to 2023, convenience sampling was used to select 195 patients with rectal cancer who underwent sphincter-preserving surgery at Peking University Third Hospital as participants. The patients were surveyed using the General Information Questionnaire, LARS Scale, Visual Analog Score, and Chinese version of Insomnia Severity Index.Results:A total of 195 questionnaires were distributed, and 156 valid questionnaires were collected, with a valid response rate of 80.00% (156/195). The incidence of LARS in 156 rectal cancer patients with sphincter-preserving surgery was 36.54% (57/156), and the incidence of severe LARS was 15.38% (24/156). Binomial Logistic regression analyses showed that gender ( OR=0.445, P=0.034) and preoperative neoadjuvant chemoradiotherapy ( OR=6.343, P<0.01) were influencing factors for the occurrence of LARS in patients with rectal cancer after sphincter-preserving surgery. Preoperative neoadjuvant chemoradiotherapy ( OR=3.322, P=0.047) and intraoperative prophylactic stoma ( OR=4.855, P=0.035) were influencing factors for severe LARS. LARS score was positively correlated with anxiety score ( r=0.238, P=0.003) and total insomnia score ( r=0.168, P=0.036) in patients with rectal cancer who underwent sphincter-preserving surgery. Conclusions:Preoperative neoadjuvant chemoradiotherapy is an independent risk factor for postoperative LARS and severe LARS in rectal cancer patients undergoing sphincter-preserving surgery. LARS is correlated with patients' anxiety and insomnia.

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