Cancer stem cells (CSCs), a small subset of cells in the tumor bulk with the ability of self-renewal and differentiation, are the key to tumor occurrence, metastasis, drug resistance and relapse. CSCs are resided in a specific microenvironment, and their number maintenance, self-renewal and differentiation are precisely regulated by the microenvironment, and the immune microenvironment is one of the most critical microenvironments for CSCs. In recent years, tumor immunotherapy has achieved great success, but drug resistance and recurrence are frequently occurred after immunotherapy. Compared with non-CSC tumor cells, CSCs harbor stronger immune escape ability, and their roles in tumor immune escape are increasingly followed. In this review, we described the discovery history and lineage sources of CSCs, focused on immune cells in the CSC microenvironment, such as tumor-infiltrating lymphocytes, tumor-associated macrophages, and tumor-associated dendritic cells, and analyzed the mechanism of CSC-immune cell interaction. Intervention strategies targeting CSCs and their immune microenvironment are also described. With the development and application of advanced technologies such as CSC-immune cell co-culture, single-cell sequencing and lineage tracing, the immune escape of CSCs can be suppressed by targeting the interaction between CSCs and immune cells or reversing the immunosuppressive microenvironment, which is expected to provide potential solutions to the problems of drug resistance and relapse in tumor immunotherapy.

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Rats ; Animals ; Parkinson Disease ; Rats, Sprague-Dawley ; AMP-Activated Protein Kinases ; Diabetes Mellitus, Type 2 ; Autophagy-Related Protein-1 Homolog

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence

Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg

Objective: To investigate the prevalence of Calodium hepaticum (C. hepaticum) in rodents and insectivores from Wuhan section of the Yangtze River in China, and to provide evidence for the prevention and treatment of hepatic Calodium infection. Methods: Rodents and insectivores were captured from three selected Yangtze River beaches using mousetraps. The three survey sites were divided into six areas according to natural conditions, with 60 mousetraps placed in each area. The liver lesions in the captured rodents were observed by the naked eye and the eggs in the liver tissue were observed by microscopic examination. Results: A total of 1 080 mousetraps were placed, and 1 075 mousetraps were retrieved, with the retrieve rate as 99.5%. A total of 101 Apodemus agrarius, 12 Rattus norvegicus, and 9 Crocidura attenuata were caught. The average density of rodents and insectivores was 10.5% and 0.8%, respectively. DNA of egg nodules from infected rodents showed 98% similarity with that of C. hepaticum 18S rRNA (LC425008.1). One Rattus norvegicus was infected with C. hepaticum, with an infection rate of 3.23% in the Erqi river beach; the other two beaches did not show the incidence of C. hepaticum. Conclusions: The monitoring of C. hepaticum in the Yangtze River beaches should be strengthened to reduce the risk of human C. hepaticum infection. Zhou Shui-Mao 1 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Jin Xian-Ling 2 Wuhan Xinzhou Schistosomiasis Control Institute, Wuhan 430015 Wang Hao 3 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Luo Hua-Tang 4 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Jia Xi-Shuai 5 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Wang ZQ, Lin XM, Wang Y, Cui J. The emerging but neglected hepatic capillariasis in China. Asian Pac J Trop Biomed 2013; 3(2): 146-147. Shen LJ, Luo ZY, Li W, Li ZH, Gao C, Yang WB, et al. Investigation on rats infected with Capillaria hepatica in Da li. Chin J Parasit Dis Con 2003; 16(5): 296-298. Fischer K, Gankpala A, Gankpala L, Bolay FK, Curtis KC, Weil GJ, et al. Capillaria ova and diagnosis of Trichuris trichiura infection in humans by Kato-Katz smear, Liberia. Emerg Infect Dis 2018; 24(8): 1551-1554. Fuehrer HP. An overview of the host spectrum and distribution of Calodium hepaticum (syn. Capillaria hepatica): Part 1-Muroidea. Parasitol Res 2014; 113(2): 619-640. Lin XM, Xu BL, ZHao XD, Li H, Huang Q, Deng Y, et al. Epidemiological investigation on Capillaria hepatica infection among little animal in Henan Province. J Pathogen Bio 2007; 2(1): 44-46. Ling HB, Pan CW, Yi WP, Huang HC, Liu QZ, Zheng XY, et al. Epidemiological and biological studies of Capillaria hepatica of rodents in Wenzhou district. J Wenzhou Med Col 2000; 30(1): 13-15. Fuehrer HP, Igel P, Auer H. Capillaria hepatica in man-an overview of hepatic capillariosis and spurious infections. Parasitol Res 2011; 109(4): 969-979. Simoes RO, Luque JL, Faro MJ, Motta E, Maldonado JR. Prevalence of Calodium hepaticum (syn. Capillaria hepatica) in Rattus norvegicus in the urban area of Rio de Janeiro, Brazil. Rev Inst Med Trop Sao Paulo 2014; 56(5): 455-457. Wang ZQ, Cui J, Wang Y. Persistent febrile hepatomegaly with eosinophilia due to hepatic capillariasis in Central China. Ann Trop Med Parasitol 2011; 105(6): 469-472. Klenzak J, Mattia A, Valenti A, Goldberg J. Hepatic capillariasis in Maine presenting as a hepatic mass. Am J Trop Med Hyg 2005; 72(5): 651-653.

OBJECTIVE: To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG). METHODS: A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy. RESULTS: The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P<0.05), while there were no significant differences between the two groups in the proportion of children with improved visual acuity or adverse reactions (P>0.05). No chemotherapy-related death was observed in either group. CONCLUSIONS Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.
Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Carboplatin ; Child ; Humans ; Optic Nerve Glioma ; Retrospective Studies ; Vincristine

As an extension of proteomics, peptidomics has been widely used in medical and biological researches. However, the effect of reproducibility of identification method on peptidomics is not yet clear. In this work, the urine sample of a healthy people was analyzed for seven times in parallel by nano-liquid chromatography-high-resolution tandem mass spectrometry. To illustrate the variability and stability among these experiments, the number of spectra, the utilization of total spectra, the number of identified peptides, the number of proteins, and the ionic strength and retention time of peptides were counted and compared. The average number of peptides was 208 and the standard deviation was 38. 7. After all of data were combined, 426 peptides belonging to 114 proteins were obtained, while only 109 peptides coming from 35 proteins were identified in each experiment, indicating that there were both an randomness and a relative stability for LC-MS analysis. Increasing the number of parallel experiments would expand the data set of peptidomics, but the rate of increase would decrease over 3 or more measurements. Compared with peptides, the results of peptidomics were more stable at protein level, indicating that proteins were more robustly peptidomics biomarker than the peptides.

OBJECTIVETo investigate the mechanism of Mycobacterium tuberculosis invasion to mouse dendritic cells (DC).

METHODSMycobacterium tuberculosis strain H37Rv was co-cultured with mouse DC2.4 cells.The mRNA expression of Toll-like receptor 2/4(TLR2/4) in DC2.4 cells was detected by fluorescent quantitative real-time PCR and the protein expression of nuclear factor κB(NF-κB) was assessed by Western blotting.The extracellular concentration of tumor necrosis factor α(TNF-α) was measured by ELISA methods during Mycobacterium Tuberculosis invasion.Indirect immunofluorescent staining and flow cytometry assay were used to detect the expression of CD80 and CD86 on DC2.4 cells before and after invasion.

RESULTSThe invasion of Mycobacterium tuberculosis in DC2.4 cells was observed after 2 h of co-incubation.The rates of invasion were (37.9±5.6)%,(51.2±7.6)%,(57.2±8.9)% and(63.9±6.8)% at 6,8,10 and 12 h after co-incubation,respectively.The mRNA expression level of TLR2 /4 was significantly increased at 6 h but decreased at 10 h after co-incubation.The expressions of NF-κB p65 and TNF-α were higher in DC2.4 cells after being invaded by 6,8,and 10 h and then gradually decreased.CD80 and CD86 expression were increased on DC2.4 at 6 h after co-incubation.

CONCLUSIONInvasion of Mycobacterium tuberculosis strain H37Rv to DC might enhance its antigen-presenting function through activation of TLR2/4-NF-kB signaling pathway.

Animals ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Cells, Cultured ; Dendritic Cells ; immunology ; metabolism ; Mice ; Mycobacterium tuberculosis ; NF-kappa B ; metabolism ; Signal Transduction ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective: To investigate the mechanism of Mycobacterium tuberculosis invasion to mouse dendritic cells ( DC ) .Methods: Mycobacterium tuberculosis strain H37Rv was co-cultured with mouse DC2.4 cells.The mRNA expression of Toll-like receptor 2/4(TLR2/4) in DC2.4 cells was detected by fluorescent quantitative real-time PCR and the protein expression of nuclear factor κB ( NF-κB ) was assessed by Western blotting .The extracellular concentration of tumor necrosis factor α( TNF-α) was measured by ELISA methods during Mycobacterium Tuberculosis invasion .Indirect immunofluorescent staining and flow cytometry assay were used to detect the expression of CD80 and CD86 on DC2 .4 cells before and after invasion .Results:The invasion of Mycobacterium tuberculosis in DC2.4 cells was observed after 2 h of co-incubation.The rates of invasion were (37.9 ±5.6)%,(51.2 ±7.6)%,(57.2 ±8.9)%and(63.9 ± 6.8)% at 6,8,10 and 12 h after co-incubation,respectively.The mRNA expression level of TLR2 /4 was significantly increased at 6 h but decreased at 10 h after co-incubation.The expressions of NF-κB p65 and TNF-αwere higher in DC2.4 cells after being invaded by 6 , 8 , and 10 h and then gradually decreased .CD80 and CD86 expression were increased on DC 2 .4 at 6 h after co-incubation .Conclusion:Invasion of Mycobacterium tuberculosis strain H37 Rv to DC might enhance its antigen-presenting function through activation of TLR 2/4-NF-kB signaling pathway .