Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Objective:To investigate the efficacy of acupuncture therapy combined with rhubarb applied to the umbilicus in the treatment of constipation in patients with stage IV-V diabetic nephropathy.Methods:Ninety stage IV-V diabetic nephropathy patients with constipation, who received treatment in Wenzhou Hospital of Traditional Chinese Medicine from December 2019 to December 2020, were included in this study. They were randomly assigned to receive either routine treatment (control group, n = 45) or routine treatment plus acupuncture therapy combined with rhubarb applied to the umbilicus (study group, n = 45). Serum motilin, gastrin, and somatostatin levels and orocecal transit time pre- and post-treatment were compared between the two groups. The constipation severity was evaluated using the Constipation Severity Scale (CSS). Quality of life was evaluated using the Patient Assessment of Constipation Quality of Life Questionnaire. Clinical efficacy was compared between the two groups. Results:The somatostatin level and orocecal transit time post-treatment in the study group were (13.66 ± 4.24) ng/L and (80.58 ± 10.11) minutes, respectively, which were significantly lower than those in the control group [(19.31 ± 6.13) ng/L, (87.16 ± 12.04) minutes, t = 5.08, 2.80, both P < 0.05]. Serum motilin and gastrin levels post-treatment in the study group were (281.07 ± 41.16) ng/L and (181.07 ± 35.16) ng/L, respectively, which were significantly higher than those in the control group [(259.64 ± 39.83) ng/L, (162.65 ± 32.83) ng/L, t = 2.51, 2.56, both P < 0.05]. The scores of the Constipation Severity Scale and the Patient Assessment of Constipation Quality of Life Questionnaire post-treatment in the study group were (10.66 ± 3.14) points and (60.14 ± 13.64) points, respectively, which were significantly lower than those in the control group [ (15.31 ± 4.13) points, (71.61 ± 14.72) points, t = 6.01, 3.83, both P < 0.05). Total response rate was significantly higher in the study group than in the control group (97.78% vs. 80.00%, χ2 = 5.51, P < 0.05). Conclusion:Acupuncture therapy combined with rhubarb applied to the umbilicus can be used to treat constipation in patients with stage IV-V diabetic nephropathy. The combined therapy can adjust the secretion of gastrointestinal tract-related hormones, shorten orocecal transit time, improve clinical symptoms, and improve clinical efficacy and quality of life.

OBJECTIVE: To analyze the effects of alterations in the expressions of methyltransferase on protein expression profiles in human nasopharyngeal carcinoma (NPC) cells and enrich the differential signaling pathways. METHODS: The total protein was extracted from -knockout cell line CNE1 and the wild-type cell line CNE1, and the differentially expressed proteins were screened by tandem mass tag (TMT) labeled protein quantification technique and tandem mass spectrometry. GO analysis was used to annotate and enrich the differentially expressed proteins, and the KEGG database was used to enrich and analyze the pathways of the differential proteins. RESULTS: With a fold change (FC)≥1.2 and < 0.05 as the screening standard, 2049 differentially expressed proteins were identified in CNE1 cells, among which 904 were up-regulated and 1145 were down-regulated. GO functional annotation results indicated that knockout caused characteristic changes in multiple biological processes (cell processes and regulation, cell movement, metabolic processes, and biosynthesis of cellular components), molecular functions (catalytic activity and molecular binding, transcription factor activity), and cellular components (cell membrane, organelle, macromolecular complex). KEGG analysis showed that the differentially expressed proteins were involved in an array of signaling pathways closely related to tumors, including MAPK, PI3K-Akt, Ras, Rap1, mTOR, Hippo, HIF-1, Wnt, AMPK, FoxO, ErbB, P53 and JAK-STAT. CONCLUSIONS knockout significantly changes the protein expression characteristics of NPC cells and affects a number of signal pathways closely related to tumors. The results provide evidence for investigation of the pathogenesis and therapeutic target screening of NPC.

Objective To detect the role of PAR2-PKA/PKCε signaling pathway in periphery neurons in the tran-sition from acute to chronic pain,and investigate the possible approach to prevent both acute and chronic pain simultane-ously. Methods SD rats were randomly divided into control group,sham model group,model group,iPAR2-1 group and iPAR2-2 group. The hyperalgesia priming model was established by injection of carrageenan and PGE2 into the left hind-paw except control and sham model group. PGE2 was administrated at 7 days after carrageenan injection. The PAR2 inhibi-tor was administrated before and after PGE2 injection separately in the iPAR2-1 group and iPAR2-2 group. The paw with-drawal thresholds(PWTs)of rats in each group was detected before and at 5 h,3 d,6 d,7 d 0.5 h,7 d 4 h,7 d 24 h after carrageenan injection. The expression level of PAR2, PKA and PKCε proteins in the dorsal root ganglion(DRG) were detected at 24 h after carrageenan injection. Results The hyperalgesia priming model was successfully generated. When PGE2 was administrated at 7 days after carrageenan injection, the hyperalgesia induced by PGE2 was significantly prolonged. The PWTs of rats in the model group were significantly lower than that of the control and sham model groups(P<0.01),though the PWTs of sham model group had no significant difference with the control on 7 d 24 h after carrageenan injection(P>0.05). The expression level of PAR2 and PKCε in the ipsilateral DRG neurons were significantly increased on 7 d 24 h after carrageenan injection,when compared with the control and sham model groups(P<0.05). PAR2 inhibi-tor prevented the prolonged hyperalgesia induced by PGE2(P<0.05)and decreased the PKCε expression in DRG neurons whenever it was given(P<0.05). However,PAR2 inhibitor did not regulate the acute inflammatory pain of PGE2 and the expression of PKA in DRG neurons(P>0.05). Conclusions Inhibition of the expression of PAR2 can prevent the tran-sition from acute to chronic pain. This effect may be related with the inhibitory effect on the activation of PAR2-PKCε sig-naling pathway in DRG neurons. However,inhibition of PAR2 can not regulate the acute pain. These may because of that the PAR2-PKA signaling pathway does not play a role in acute pain.

Objective To detect the expression level of aquaporin 8 (AQP8) in patients with functional constipation(FC) or constipated irritable bowel syndrome (IBS-C),and the correlation between the expression of AQP8 and clinical features.Methods From March to December 2014,a total of 16 patients with IBS-C and 19 patients with FC met Rome Ⅲ criteria were collected,and nine healthy individuals were assigned to control group at the same period.The ascending and decending colonic tissues mucosa of FC,IBS-C and control group were taken under endoscope.The expression of AQP8 at mRNA and protein level was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).The differences in AQP8 mRNA expression and AQP8 relative area were analyzed by Kruskal-Wallis test among groups,and Pearson correlation coefficient was performed for correlation analysis between the expression and clinical features.Results The relative expressions of AQP8 mRNA of ascending colon and descending colon of FC patients (1.38,0.61 to 4.09;2.65,0.82 to 7.52) and IBS-C patients (2.23,0.82 to 4.67;1.35,0.51 to 2.03) were higher than those of control group (0.56,0.19 to 0.97;0.38,0.21 to 1.19),and the differences were statistically significant (ZFc =-2.435,-3.149,ZIBS-C =-2.690,-2.152;all P＜0.05).AQP8 mRNA expression of descending colon in patients with FC was higher than that of patients with IBS-C,and the difference was statistically significant (Z =-2.003,P =0.045).The expression of AQP8 in patients with FC and IBS-C was positively correlated with disease course (ascending colon r=0.57 and 0.53;descending colon r=0.49 and 0.54,all P＜0.05),and was negatively correlated with frequency of defecation (ascending colon r=-0.82 and-0.61;descending colon r=-0.49 and-0.53,all P＜0.05).There was no correlation between the expression of AQP8 and age,gender,onset age,presence of abdominal symptoms of the patients (all P＞ 0.05).Most of AQP8 of FC group was expressed in cytoplasm of colonic mucosa epithelial cells,while that of IBS-C group and control group was mostly expressed at apical membrane and basal membrane of epithelial cells.The results of semi-quantification demonstrated that AQP8 relative area of descending colon of FC and IBS-C group increased compared with that of control group (3.42％ (1.24％ to 5.61％),2.45％(1.72％ to 4.27％) vs 1.18％ (0.35％ to 2.81％);Z=-2.534,-2.151,both P＜0.05).Meanwhile,AQP8 relative area of ascending colon of FC group increased compared with that of control group (2.46％(1.48％ to 4.18％) vs 1.14％(1.29％ to 2.15％) Z=-2.041,P＜0.05).Conclusion There are differences in AQP8 expression quantity and location in cells of descending colon between patients with FC and patients with IBS-C,which is a way for differentiation these two diseases.

To determine the relevance between MDCT features and anatomic-pathological basis of lymphoid neoplasm in cervico-thoracic junctional region, we performed a retrospective analysis of 69 patients with lymphoid neoplasm (lymphoma: 41 patients; metastatic tumor: 28 patients) involving the cervico-thoracic junctional region for MDCT features and distribution of lesions. The relevance between MDCT features and the anatomic-pathological basis in this region were evaluated. Among all the 41 patients with lymphoma, 29 with NHL (70.7%), 12 with HD (29.3%). The lymphomatous lymphadenopathy mainly located in superficial lateral cervix (51.2%, 21/41) ,deep jugular chain (65.9%, 27/41), supraclavicular fossa (75.6%, 31/41), paratrachea space in anterior mediastinum (46.3%, 19/41), around aortic arch (56.1%, 23/41), aortopulmonary window (53.7%, 22/41), upper anterior mediastinum (41.5%, 17/41), subcarinal space (26.8%, 11/41) and paraesophageal space (17.1%, 7/41). 28 patients had metastatic lymphoid tumor. The primary tumor were nasopharynx tumor (5 patients), thyroid cancer (7 patients), lung cancer (10 patients), and esophageal cancer (6 patients). Most metastasis took stage by stage in the way of lymphatic return, but a minority of cases migrated jumpily. The main metastatic sites were: beside jugular chain (82.1%), supraclavicular fossa (75%), paratracheal in anterior mediastinum (60.7%), upper anterior mediastinum (64.3%), beside aortic arch (35.7%), aortopulmonary window (39.2%), and paraesophageal space (28.6%). So lymphoid neoplasms in cervico-thoracic junctional region were involving both lower cervix and upper thorax simultaneously. The MDCT features and main distribution of lesions correlated with the anatomic-pathological characteristics in this region.
Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; diagnostic imaging ; Lymphoma ; diagnostic imaging ; Male ; Middle Aged ; Multidetector Computed Tomography ; Neck ; Thorax ; Young Adult