1.Construction of mouse intestinal organoid inflammation model
Hao CHEN ; Rui LI ; Fei YI ; Li ZHOU ; Jiaqi CHEN ; Fan ZHU ; Chengyan GUAN ; Na WU
Tianjin Medical Journal 2024;52(1):16-21
Objective To establish in vitro the small intestinal organoid culture system and to investigate the effect of lipopolysaccharide(LPS)on the growth of small intestinal organoids and the secretion of inflammatory factors.Methods In vitro,the small intestinal crypt cell mass of C57BL/6 mice was aseptically isolated,collected and embedded in organoid matrix.Under the support of complete medium,the small intestinal organoids with three-dimensional multi-leaf structure with small intestinal epithelioid structure were formed.The small intestinal organoids were subcultured after 5-7 d culture.On the third day after passage,the small intestinal organoids were randomly divided into different mass concentrations of LPS groups(0,150,175,200,225,250,275 and 300 mg/L).After 24 h and 48 h of LPS induction,morphological changes of small intestinal organoid growth and differentiation were observed.CCK-8 method was used to detect the effect of different time points and mass concentrations of LPS on the proliferative activity of small intestinal organoids after induction of inflammation.The effects of four different mass concentrations of LPS(0,175,200 and 225 mg/L)on expression levels of granulocyte-macrophage colony stimulating factor(GM-CSF),interleukin(IL)-1α,IL-6 and IL-10 in organoid culture supernatant at different times were detected by enzyme-linked immunosorbent assay(ELISA).Results The mouse small intestinal organoid culture system was preliminarily constructed.After different time and mass concentration of LPS induced inflammation of small intestinal organoids,it was observed by morphology that small intestinal organoids would have different degrees of expansion and apoptosis in lumen.The proliferation,differentiation and budding of damaged intestinal epithelial crypts or intestinal stem cells were also inhibited to varying degrees,indicating that the growth of small intestinal organoids would be limited to varying degrees after induced inflammation.The proliferation activity of small intestinal organoids decreased to varying degrees after 24 h and 48 h of LPS induction at 175-225 mg/L(P<0.05),but the cell viability was still greater than 50%.The levels of IL-1α,IL-6 and GM-CSF partially increased after induction with 200 mg/L and 225 mg/L LPS for 24 h and 48 h(P<0.05).The level of IL-10 decreased after induction with 200 mg/L LPS for 24 h and 48 h(P<0.05).Conclusion In this study,a model of intestinal inflammatory injury in vitro induced by LPS with different mass concentrations and time points is preliminarily constructed,which provides a more reliable research platform for the mechanism research of intestinal diseases and the screening of effective drugs in the future.
2.Role of uropathogenic Escherichia coli virulence factor TcpC in immune evasion and its pathogenic mechanism
Weiyu JIANG ; Jiaying FAN ; Liming FAN ; Jiadong WANG ; Ziyan JIANG ; Ziyu GUAN ; Qian OU ; Jiaqi FANG
Chinese Journal of Microbiology and Immunology 2024;44(3):198-204
Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in immune evasion, and analyze its related pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 colony-forming unit of wild-type (CFT073 wt) or tcpc gene-knockout (CFT073 Δ tcpc) UPEC CFT073 strains from urethra into bladder to construct a mouse model of pyelonephritis. These mice were sacrificed 5 d after infection and their kidneys were taken to observe the gross pathological changes. Hematoxylin-eosin staining was used to observe histopathological changes in kidney tissues and immunohistochemistry was performed to locate TcpC in kidney tissues. The bacterial loads in urine samples of UPEC infected-mice were counted by ten-fold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from CFT073-infected mouse kidney or urine samples was measured by PCR. The expression of TcpC at mRNA level was detected by qRT-PCR after infecting dendritic cells with CFT073 wt strains. The influences of UPEC infection on the activation of NF-κB signaling pathway and the secretion of proinflammatory factors by dendritic cells were analyzed by Western blot and ELISA, respectively. The viability of UPEC strains in dendritic cells were observed by laser confocal microscope. Results:Compared with the CFT073 Δ tcpc group, the mice in the CFT073 wt group had obvious abscess in the kidneys as well as massive neutrophil infiltration and abundant TcpC in kidney tissues. The bacterial loads in the urine of CFT073 wt-infected mice were significantly higher than those in the urine of CFT073 Δ tcpc mice. PCR results showed that tcpc gene was successfully amplified from mouse kidney and urine samples. Increased expression of TcpC at both mRNA and protein levels was detected in CFT073 wt-infected dendritic cells. CFT073 wt infection inhibited the phosphorylation of NF-κB p50 and the production of proinflammatory factors in dendritic cells. TcpC promoted the survival of CFT073 wt in dendritic cells. Conclusions:TcpC expression increases significantly during CFT073 wt infection or in mice with CFT073 wt-induced pyelonephritis. It promotes the survival of CFT073 wt in dendritic cells by inhibiting the activation of NF-κB signaling pathway and reducing the secretion of pro-inflammatory cytokines. TcpC is involved in the pathogenesis of UPEC and immune evasion.
3.Four Cases of Atypical Teratoid/Rhabdoid Tumor of Lateral Ventricles in Children
Jiaqi FENG ; Xinyao WANG ; Lei BAO ; Wenbin GUAN ; Yabing ZHOU ; Xiaoqiang WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(3):655-660
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy located primarily in infratentorial or subcortical areas with a poor prognosis, and rarely in the lateral ventricle with a very poor prognosis. So far, only 6 cases of AT/RT in lateral ventricle have been reported in China. This article reports the diagnosis and treatment of four children with AT/RT in the lateral ventricle, and discusses the clinical manifestations, differentiation and diagnosis, treatment and prognosis of the disease through literature review, in order to improve clinicians' understanding of the disease and reduce missed diagnosis and misdiagnosis.
4.Clinical efficacy and safety of kyphoplasty for the treatment of osteoporotic vertebral compression fractures at different surgical timings based on the theory of “dynamic-static integration”
Zunwang Li ; Jiang Chen ; Dekui Li ; Jiayu Yang ; Jiaqi Qin ; Yuqing Guan
Journal of Traditional Chinese Medical Sciences 2024;11(1):86-92
Objective:
To investigate the clinical efficacy and safety of percutaneous kyphoplasty at different surgical timings in the treatment of osteoporotic vertebral compression fracture (OVCF) based on the theory of “dynamic-static integration”.
Methods:
Patients with OVCF who underwent percutaneous kyphoplasty in our hospital were selected and divided into Groups A, B, and C for those undergoing surgery within 7, 7–21, and >21 days of fracture occurrence. The variations in the amount of bone cement injected, pre- and post-operative pain levels, functional activity, deformity correction of the injured vertebrae, bone cement leakage, and vertebral body height loss were compared among the three groups.
Results:
Regarding pain relief and functional activity, the postoperative Visual Analog Scale and Oswestry Disability Index scores of the three groups significantly improved. Furthermore, the deformities of the injured vertebrae in the three groups were significantly corrected, with Groups A and B exhibiting superior correction compared to Group C. Moreover, the bone cement leakage rates in groups A and C were higher than that in Group B. At the 3-month follow-up, the loss of vertebral height in Group C was significantly higher than those in groups A and B.
Conclusion
Kyphoplasty is effective for OVCF treatment. Early surgery can effectively restore the vertebral height of the injured vertebra, reduce kyphosis, and reduce height loss of the injured vertebra after surgery; nevertheless, treatment within 1–3 weeks of the fracture can reduce the occurrence of bone cement leakage, making the surgery safer. Therefore, surgical treatment within 1–3 weeks of fracture is safer and can achieve satisfactory therapeutic effects. From the perspective of traditional Chinese medicine, PKP surgery can transform the fracture end from a micromotion state to a fixed state, which fully embodies the theory of “dynamic-static integration”.
5.Clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand
Chan ZHU ; Lin HE ; Ting HE ; Ying LIANG ; Bowen ZHANG ; Haiyang ZHAO ; Hao GUAN ; Xuekang YANG ; Dahai HU ; Juntao HAN ; Jiaqi LIU
Chinese Journal of Burns 2024;40(4):365-372
Objective:To explore the clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand.Methods:This study was a retrospective non-randomized controlled study. From February 2015 to February 2023, 24 patients (15 males and 9 females, aged 12-55 years) with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand, who met the inclusion criteria and were repaired with flap transplantation and tendon grafting or tendon anastomosis, were admitted to the First Affiliated Hospital of Air Force Medical University. According to different intervention time for postoperative rehabilitation treatment of patients, the patients were divided into conventional rehabilitation group and early rehabilitation group, with 12 cases in each group. Patients in early rehabilitation group received rehabilitation treatment immediately after surgery under the rehabilitation guidance of specialized rehabilitation physicians based on the characteristics of different postoperative periods. Patients in conventional rehabilitation group began rehabilitation treatment from the third week after surgery, and their rehabilitation treatment was the same as that of patients in early rehabilitation group from the second week after surgery. The patients in 2 groups were treated in the hospital until the sixth week after surgery. The occurrence of flap vascular crisis and tendon rupture were observed within 6 weeks after surgery. After 6 weeks of surgery, the manual muscle test was used to measure the pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, and grip force of the affected hand; the total action motion method was used to evaluate the finger joint range of motion of the affected hand, and the excellent and good ratio was calculated; the Carroll upper extremity function test was used to score and rate the function of the affected hand.Results:Within 6 weeks after surgery, only 1 patient in conventional rehabilitation group suffered from venous crisis, and the flap survived after the second surgical exploration and anastomosis of blood vessels; there was no occurrence of tendon rupture in patients of 2 groups. After 6 weeks of surgery, there were no statistically significant differences in pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, or grip force of the affected hand between the two groups of patients ( P>0.05); the excellent and good ratio of the finger joint range of motion of the affected hand of patients in early rehabilitation group was 11/12, which was higher than 7/12 in conventional rehabilitation group, but there was no statistically significant difference ( P>0.05); the affected hand function score of patients in early rehabilitation group was 90±6, which was significantly higher than 83±8 in conventional rehabilitation group ( t=2.41, P<0.05); the function rating of the affected hand of patients in early rehabilitation group was obviously better than that in conventional rehabilitation group ( Z=2.04, P<0.05). Conclusions:Early rehabilitation treatment for patients with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand after repair surgery can improve hand function, but it would not increase surgery related complications, which is worthy of clinical promotion and application.
6.Prognostic impacts of the estimated dose of radiation to immune cells (EDRIC) on limited-stage small-cell lung cancer with different tumor burdens
Jianian LAI ; Song GUAN ; Meng YAN ; Chunliu MENG ; Zhen ZHANG ; Jiaqi ZHANG ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2023;32(7):584-591
Objective:To investigate the effects of estimated dose of radiation to immune cells (EDRIC) on overall survival (OS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) in limited-stage small-cell lung cancer (LS-SCLC) with different tumor burdens.Methods:Clinical data of 216 patients with LS-SCLC who initially received conventional fractionated radiotherapy of the chest for radical treatment in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were retrospectively analyzed. EDRIC was calculated based on the model developed by Jin et al. and tumor burdens were assessed by gross tumor volume (GTV) or clinical stage. The study endpoints were OS, LPFS and DMFS, which were calculated from the date of diagnosis. The optimal cut-off value of EDRIC was calculated by R language. The correlation between EDRIC and tumor burdens was analyzed using Spearman's correlations. Survival analysis was performed by Cox proportional hazards regression model and Kaplan-Meier curve. Results:The median follow-up time for the whole group was 47.8 months, and the median OS and DMFS was 34.6 months and 18.5 months, respectively, while the median LPFS did not reach. The optimal cut-off value of EDRIC was 6.8 Gy. Cox multivariate analysis showed that EDRIC was an independent prognostic factor affecting OS and DMFS. EDRIC was weakly correlated with GTV or clinical stage. Stratified by the median GTV, OS ( P=0.021) and DMFS ( P=0.030) were significantly shortened and LPFS had a tendency of shortening ( P=0.107) when EDRIC>6.8 Gy compared with those when EDRIC ≤ 6.8 Gy in the GTV ≤ 34.6 cm 3 group; EDRIC had little effect on OS, LPFS, and DMFS ( P=0.133, 0.420, 0.374) in the GTV>34.6 cm 3 group. Stratified by clinical stage, OS ( P=0.003) and DMFS ( P=0.032) were significantly shortened and LPFS ( P=0.125) tended to shorten when EDRIC>6.8 Gy in stage I, II and IIIA groups; EDRIC exerted slight effect on OS, LPFS, and DMFS ( P=0.377, 0.439, 0.484) in stage IIIB and IIIC groups. Conclusion:EDRIC is an important factor affecting prognosis and exerts more significant impact on prognosis in patients with smaller tumor burden.
7.Research progress on the correlation among fibrinogen ,D‐dimer and cerebral infarction/
Jiaqi LI ; Zhuoya GUAN ; Feng LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2019;28(6):107-110
Cerebral infarction is a frequent type of cerebrovascular disease .It has the characteristics of high morbidi‐ty ,high mortality ,high disability rate and high recurrence rate .Fibrinogen and D‐dimer are closely associated with occurrence ,severity and prognosis of cerebral infarction .The present article summarizes research progress on the correlation among fibrinogen ,D‐dimer and cerebral infarction at home and abroad .
8.Research progress of clinical and imaging study of corpus callosum infarction /
Zhuoya GUAN ; Jiaqi LI ; Wenzhao ZHANG ; Xiaoyue ZHU ; Feng LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2019;28(6):110-113
The corpus callosum is the largest white matter structure in encephalic structure , which mainly provides communication between the hemispheres .Clinical manifestations of its infarction are complex and diverse ,including symptoms such as corpus callosum disconnection syndrome and speech disorders .Due to the lack of exact localization signs ,clinical imaging techniques are often used to improve diagnosis rate .Therefore ,the present article reviews clinical and imaging features of patients with corpus callosum infarction in order to improve the understanding and diagnosis of corpus callosum infarction .
9.Progress on PD-1/PD-L1 Checkpoint Inhibitors in Lung Cancer.
Di ZHANG ; Jiaqi HUANG ; Chufeng ZHANG ; Yan GUAN ; Qisen GUO
Chinese Journal of Lung Cancer 2019;22(6):369-379
In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers.
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Animals
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Antineoplastic Agents, Immunological
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therapeutic use
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B7-H1 Antigen
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antagonists & inhibitors
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genetics
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immunology
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Humans
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Immunotherapy
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Lung Neoplasms
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drug therapy
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genetics
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immunology
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Programmed Cell Death 1 Receptor
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antagonists & inhibitors
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genetics
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metabolism
10.The Zhejiang School of Chinese Medicine:Its Orgin,Development and Academic Characteristics
Journal of Zhejiang Chinese Medical University 2018;42(1):64-67
[Objective]To explore the orgin,development and academic characteristics of the Zhejiang school of Chinese materia medica.[Method]To research literature and inquire historic human heritages of the Zhejiang school of Chinese materia medica,analyze historical figures,sum up the academic ideology. [Result]The history of the Zhejiang school of Chinese materia medica can be up to 8,000 years ago.According to preliminary statistics,the Zhejiang School of Chinese materia medica works are about more than 170.The representatives are Tong Jun,FAN Li,WEI Boyang,CHEN Cangqi,CHEN Shiwen,LU Fu,ZHANG Zhicong,WU Yiluo,ZHAC Xueming,and so on.The academic characteristics of the Zhejiang school are focused on innovation,pragmatism,respect for classics, using fresh and cool medicine.[Conclusion] Zhejiang area is rich in medicinal resources,and Zhejiang has a large numble of talents.Since ancient times, intellectuals of Zhejiang believe that"either to be a good prime minister or to be an excellent doctor".So it has made a great quantity of persons with ability in the Zhejiang school,and an immense number of books,and formed with its own distinctive academic characteristics of Ethnopharmacology which is focused on innovation,pragmatism,respected for classics,using fresh and cool medicine.The Zhejiang school of Chinese materia medica has made an outstanding contribution to the cause of Chinese medicine,and occupied an important position.


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