Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.

Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.

OBJECTIVE: To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells. METHODS: Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting. RESULTS: The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P < 0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P < 0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P < 0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P < 0.05), and HSDL2 silencing produced the opposite effects (P < 0.05). CONCLUSION The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.
Humans ; CA-19-9 Antigen ; Ki-67 Antigen/metabolism* ; Prospective Studies ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Rectal Neoplasms/genetics* ; Cell Cycle ; Gene Expression Regulation, Neoplastic ; Hydroxysteroid Dehydrogenases/metabolism*

Relativity between prescription and syndrome is a theory of clinical syndrome differentiation by exploring the inherent laws between prescriptions and diseases， and it is also a unique syndrome differentiation thoughts， which is the core and essence of syndrome differentiation and treatment. Relativity between prescription and syndrome was initially recorded in Treatise on Febrile Diseases（《伤寒论》）. Prescriptions include empirical prescription， classic prescription， and current prescription. Syndrome is symptom， but also pathogenesis. Relativity between prescription and syndrome means that the prescription corresponds to pathogenesis. The disease manifests itself differently in different patients， meanwhile the symptom changes at different stages. Therefore， simply applying the original classic prescription cannot better reflect the syndrome differentiation principle of “changing treatment with syndromes”， nor does it solve complex clinical problems. Mastering the principle of relativity between prescription and syndrome can improve the accuracy of the syndrome differentiation and understand the constant changes， thus grasping the core and essence of the syndrome differentiation. The classic prescription and its syndrome have the most fixed relationship， so that the classic prescription can be used as a typical representative to explore the relativity between prescription and syndrome. Based on Treatise on Febrile Diseases， this paper summarized the relativity between prescription and syndrome into nine principles， including using medical classics to classify syndromes， using prescriptions to classify syndromes， focusing on the main syndromes， changing prescriptions when the main syndromes change， changing medicines with syndrome changing， modifying prescriptions according to syndromes， changing dosage according to syndromes， syndrome differentiation according to pulse， and syndrome differentiation according to time. Through analyzing the content in Treatise on Febrile Diseases， this paper described the application of the nine principles to explore the scientific connotation and improve the accuracy of syndrome differentiation， thereby expanding the range of classic prescription applications and providing references for the flexibly application of classic prescriptions and improvement of clinical efficacy.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Objective:To investigate the level of trimethylamine N-oxide (TMAO), one of gut metabolites, in patients undergoing maintenance hemodialysis (MHD) accompanied by congestive heart failure (HF) and its influencing factors.Methods:Those patients of 18-75 years old who received three or more times of hemodialysis sessions per week for three months or longer during Nov 2018 and Mar 2019 were enrolled. Those attended health checkup at the same time without obvious kidney abnormality served as non-kidney disease controls. Serum TMAO concentrations were measured using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). The levels of TMAO were compared between patients on hemodialysis and controls, between those with heart failure and without heart failure using logrithmically transformed TMAO (lnTMAO). Linear regression analysis was performed to investigate factors influencing TMAO levels.Results:A total of 195 patients undergoing MHD and 40 controls were enrolled. Among them, 30 hemodialysis cases (15.4%) manifested as heart failure symptoms and/or left ventricular ejection fraction less than 50%. Males accounted for 67.2% in patients on hemodialysis and 37.5% in controls ( χ2=12.426, P<0.001) respectively, while the median ages in both groups were 62.0(48.0, 71.0), 45.0(33.3, 55.0) years old respectively ( Z=5.685, P<0.001). TMAO concentrations were significantly higher in patients on hemodialysis than controls [5.54(3.84, 8.91) mg/L vs 0.17(0.11, 0.30) mg/L, after log transformed, t=21.687, P<0.001]. However, there was no statistically significant difference between those with heat failure and those without in male [63.3% vs 67.9%, χ2=0.238, P=0.626], age [64.5(56.8, 71.0) years old vs 61.0(47.0, 72.0) years old, Z=0.894, P=0.372] and TMAO [5.17(3.30, 9.46) mg/L vs 5.57(3.87, 8.95) mg/L, after log transformed, t=-1.537, P=0.135]. Multivariate linear regression analysis demonstrated that in all the participants, serum urea was the main risk factor for TMAO [standardized coefficient ( SB)=0.483]. lnTMAO=0.078×[serum urea(mmol/L)]+0.001×[serum creatinine (μmol/L)]-0.002×[serum uric acid (μmol/L)]-0.003×[platelet (×10 9/L)]+0.014×[age (years old)]+0.344 (if diabetic)-1.266. While in those undergoing MHD, ultrafiltration volume had the most significant effect on TMAO levels ( SB=0.279). lnTMAO=0.249×[ultrafiltration volume(L)]+0.059×[serum albumin (g/L)]+0.008×[age (years old)-0.526 (if heart failure existed)-1.865. Conclusions:MHD patients have gut dysbiosis, while those hemodialysis patients accompanied by heart failure may have peculiar gut microbiota which induces lower serum TMAO levels than those without heart failure after adjusting for multiple related factors. Serum TMAO levels may be associated with ultrafiltration volume and nutrition status etc.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
Animals ; Cell Death ; Cell Line, Tumor ; Ferroptosis ; Lung Neoplasms/drug therapy* ; Mice ; Orlistat

Objective:To evaluate the effectiveness and safety of Chinese herbal medicines (CHMs) for incomplete immune reconstruction in patients with HIV/AIDS.Methods:Eight electronic databases were searched for randomized controlled trials (RCTs) on the use of CHM for patients with HIV/AIDS with incomplete immune reconstruction.Outcomes included CD4+ cell count,quality of life,and adverse events/effects.The Cochrane Risk of Bias was employed to evaluate the methodological quality of the included RCTs.Results:We identified 13 eligible RCTs,with an overall high risk of bias,on 10 different CHMs.There was a significant increase in CD4+ cell count after the use of Jianpi Yiqi medicinal paste for 3 months;tripterygium glycosides tablets (TGTs) for 3 months (mean difference[MD]52.63 cells/μL,95％ confidence interval[CI,46.98,58.28]),6,9,and 12 months;Wenshen Jianpi granules for 6 months;Shenling Fuzheng capsules for 6 months (MD 49.53 cells/μL,95％ CI[8.45,90.61]) and 12 months;Aikeqing granules for 9 months (MD 61.51 cells/μL,95％ Cl[16.25,106.77]) and 12 months;Guipi decoction for 12 months;Mianyi No.2 granules (JT) for 12 and 18 months;and Chinese medicine granules for 18 months.The increase in the mean difference ofCD4+ cell count from 6 to 18 months was larger in Chinese medicine granules and Mianyi No.2 granules (JT).Guipi decoction and Jianpi Qushi decoction improved the Karnofsky score.Four RCTs reported the outcome of adverse events/effects,while four cases of minor adverse effects were reported in the TGTs group.Conclusion:Jianpi Yiqi medicinal paste,Wenshen Jianpi granules,Shenling Fuzheng capsules,Aikeqing granules,Guipi decoction,and TGTs may be effective in increasing CD4+ within 12 months,and Mianyi No.2 granules (JT) and Chinese medicine granules may show long-term effects.High-quality large RCTs on the effectiveness and safety of CHMs are still warranted.

Objective To investigate the causes of misdiagnosis related to rheumatism diseasecases.Methods A search was performed in database WanFang to identify the misdiagnosed clinical cases reports which were published in Chinese Journal and a retrospective analysis was conducted.All data were analyzed by chi-square test and Fisher's exact test.Results We screened 705 citations and identified 215 articles on the rheumatic diseases,finally,187 reports and 195 cases in total with definite diagnosis were included,accounting for 25.5％ of the total number of misdiagnosed cases.Primary vasculitis (72 cases),rheumatoid arthritis (25 cases),spondyloarthropathy (17 cases),polymyositis (14 cases),systemic lupus erythematosus (13 cases) and Sj(o)gren's syndrome (SS) (12 cases) were amongst the top misdiagnosed rheumatic diseases.There was no difference between 1998-2006 and 2007-2015 in the overall misdiagnosis cases.Single disease comparison,polymyositis,spondyloarthropathy and IgG4 related disease were increased (P=0.002;P=0.034;P=0.060;respectively),while polymyositis was delayed (P=0.002).Rheumatism misdiagnosed cases reported mainly came from tertiary hospitals and the department of rheumatology.Conclusion Misdiagnosed rheumatism are common in clinic.Strengthen the physicians' continuous education,the validity of clinical thinking mode and rational use of diagnostic criteria are important to make correct diagnosis.

OBJECTIVETo evaluate and compare the value of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder.

METHODSFrom September 2014 to July 2015, a prospective controlled trial was carried out in Chengdu Anorectal Hospital. A total of 32 patients met the inclusion criteria of functional defecation disorder simultaneously underwent pelvic four-contrast defecography and dynamic multiple pelvic angiography. The diagnostic results of these two methods were compared.

RESULTSThe absolute values of anorectal angle and level of perineum, peritoneum and bladder from rest to defecation were (29.6±13.6)°, (26.2±14.2) mm, (55.5±25.6) mm and (28.9±16.5) mm in dynamic multiple pelvic angiography, and (24.6±5.8)° (18.7±10.6) mm, (34.5±18.4) mm and (19.2±11.8) mm in pelvic four-contrast defecography respectively, whose differences were statistically significant (P = 0.026, 0.022, 0.000, 0.011 respectively). The diagnostic rate of pelvic peritoneal hernia was 93.8%(30/32) and 68.8%(22/32) in dynamic multiple pelvic angiography and pelvic four-contrast defecography respectively with significant difference(P=0.011).

CONCLUSIONDynamic multiple pelvic angiography has significant advantage in the diagnosis of pelvic peritoneal hernia, and can provide a more objective basis for the diagnosis of functional defecation disorder.

Angiography ; methods ; Constipation ; diagnosis ; Defecation ; Defecography ; methods ; Humans ; Pelvis ; Perineum ; Prospective Studies