Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation.

Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results: We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion: We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted.

Investigation of Tongxie-Yaofang formula in treating ulcerative colitis based on network pharmacology via regulating MAPK/AKT signaling pathway.

BACKGROUND: Ulcerative colitis (UC) is a subtype of inflammatory bowel disease, which often leads to bloody diarrhea and abdominal pain. In this study, the function mechanism of Tongxie-Yaofang formula (TXYF) on UC was investigated. METHODS: Action targets of TXYF were obtained by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) databases. The targets of UC were screened in Gene Cards and Online Mendelian Inheritance in Man (OMIM) databases. The network pharmacology of active ingredient targets was established via Cytoscape. RESULTS: A total of 42 chemical components and 5806 disease targets were obtained. The GO functional analysis showed that biological processes such as oxidative stress and molecular response to bacteria, molecular function such as protein and nucleic acid binding activity were significantly enriched. The top 20 KEGG enriched signal pathways indicated that the targets were mainly linked with IL-17, TNF, HIF-1. Molecular docking results showed that naringenin had good binding activity between naringin and MAPK, albiflorin and SRC. The activity of MPO, the concentration of HIF-1, IL-17 and TNF-α were significantly decreased after TXYF treatment. The characteristics of UC such as crypt distortion, crypt atrophy, and increased basal plasmacytosis were also less observed with the treatment of TXYF. What's more, TXYF suppresses the phosphorylation of SRC, MAPK and AKT1 in UC. CONCLUSIONS: TXYF showed treatment effect on UC through multiple components and multiple targets, which lays a foundation for further study of UC treatment.

A novel fluorescent sensor with an overtone peak reference for highly sensitive detection of mercury (II) ions and hydrogen sulfide: Mechanisms and applications in environmental monitoring and bioanalysis.

The present study introduces a novel fluorescent sensor with an overtone peak reference designed for the detection of mercury (Ⅱ) ions (Hg2+) and hydrogen sulfide (H2S). The study proposes two novel response mechanisms that hinges on the synergistic effect of cation exchange dissociation (CED) and photo-induced electron transfer (PET). This sensor exhibits a remarkable detection limit of 2.9 nM for Hg2+. Additionally, the sensor reacts with H2S to generate nickel sulfide (NiS) semiconductor nanoparticles, which amplify the fluorescence signal and enable a detection limit of 3.1 nM for H2S. The detection limit for H2S is further improved to 29.1 pM through the surface functionalization of the nanomaterial with pyridine groups (increasing reactivity) and chelation of gold nanoparticles (AuNPs), which enhances the sensor's specificity. This improvement is primarily due to the surface plasmon resonance (SPR) of AuNPs and their affinity for H2S. The single-emission strategy can yield skewed results due to environmental changes, whereas the overtone peak reference strategy enhances result accuracy and reliability by detecting environmental interference through reference emission peaks. In another observation, the low-toxicity dihydropyrene-bipyridine nanorods (TPP-BPY) has been successfully utilized for both endogenous and exogenous H2S detection in vivo using a mouse model. The successful development of TPP-BPY is expected to provide an effective tool for studying the role of H2S in biomedical systems.

Comparison of high or modified low tie of the inferior mesenteric artery in laparoscopic rectal cancer surgery: A meta-analysis.

OBJECTIVE: The purpose of this study was to perform a meta-analysis comparing the oncological, intraoperative and safety outcomes in laparoscopic rectal cancer surgery with and without preservation of the left colic artery (LCA). METHOD: We searched several databases including PubMed, Web of Science, Cochrane Library, and Embase databases. This meta-analysis included randomized clinical trials, prospective, and retrospective comparative studies regarding high- or modified low-tie ligation of the inferior mesenteric artery in laparoscopic rectal cancer surgery. RESULTS: Of 641 potentially eligible articles, 16 studies with 3050 participants met the eligibility criteria and were included in the meta-analysis. There was no significant difference in estimated blood loss (WMD -2.63, 95% CI -5.69 to 0.43; P = .09), the number of harvested lymph nodes (WMD -0.35, 95% CI -1.60 to 0.20; P = .50), the number of apical lymph node yield (WMD -0.19, 95% CI -0.52 to 0.13; P = .24), the number of apical lymph node metastasis (OR 0.76, 95% CI 0.40 to 1.45; P = .40), rate of conversion to open surgery (OR 0.74, 95% CI 0.50 to 1.09; P = .513), rate of urinary dysfunction (OR 1.39, 95% CI 0.71 to 2.74; P = .34), rate of recurrence and metastasis (OR 1.10, 95% CI 0.75 to 1.61; P = .64), 5-year survival rate (OR 0.89, 95% CI 0.67 to 1.18; P = .42). However, this meta-analysis demonstrated a statistically significant difference in operating time (WMD -9.92, 95% CI -15.49 to -5.84; P = .0005), rate of diverting stom (OR 1.42, 95% CI 1.06 to 1.92; P = .02), rate of anastomotic leakage (OR 2.673, 95% CI 1.91 to 3.62; P < .00001), time to first flatus (WMD 0.29, 95% CI 0.11 to 0.48; P = .002), time of hospitalization (WMD 0.64, 95% CI 0.14 to 1.15; P = .01) between the 2 surgical techniques. COCLUSION: The available evidence suggests that preserving the left colic artery is a safe, effective technique for patients with laparoscopic rectal cancer. nique for patients with laparoscopic rectal cancer.

Correlation between TCM Constitutional Types and Lung Carcinoma in Various Geographical Areas: A Systematic Review and Meta-Analysis.

Background: Lung carcinoma is a serious disorder that negatively influences the quality of life of sufferers. Despite the growing number of investigations into the management and prognosis of lung carcinoma, few research studies have been conducted to demonstrate the association between TCM constitution and lung carcinoma. Methods: We searched PubMed, EMBASE, Science Net, Cochrane Library, China National Knowledge Infrastructure, VIP database, Wanfang database, and China Biomedical Literature Database for Chinese and English versions until January 31, 2021. We also manually searched for Chinese lung cancer, Chinese physical medicine, Chinese medical trial registries, and unpublished surveys or references. The literature was screened against inclusive and exclusive criteria, and two investigators' results were independently summarized. The primary outcome was a ratio of body type. Single-group rates were meta-analyzed using Stata 14.0 statistical software, bias was estimated by funnel plotting, and sources of heterogeneity were evaluated by subgroup and sensitivity examinations. Results: 18 randomized controlled trials were totally included to compare the single-group ratio and 95% confidence interval of nine constitution types of lung cancer, namely, mild constitution (ES = 0.12, 95% CI (0.08, 0.15), P < 0.0001), Qi deficiency constitution (ES = 0.20, 95% CI (0.15, 0.26), P < 0.0001), Qi depression constitution (ES = 0.09, 95% CI (0.07, 0.12), P < 0.0001), damp-heat constitution (ES = 0.05, 95% CI (0.03, -0.06), P < 0.0001), phlegm dampness constitution (ES = 0.05, 95% CI (0.03, -0.06), P < 0.0001), special constitution (ES = 0.01, 95% CI (0.01, 0.02), P=0.993), blood stasis constitution (ES = 0.05, 95% CI (0.04, 0.07), P < 0.0001), Yang deficiency constitution (ES = 0.16, 95% CI (0.12, 0.19), P < 0.0001), and Yin deficiency constitution (MD = 0.15, 95% CI (0.11, 0.18), P < 0.0001). Conclusion: This study showed that Qi deficiency, Yang deficiency, and Yin vacuity were the predominant types of physical conditions of lung cancer cases.

LAP+CD4+T cells regulate the anti-tumor role of CIK cells in colorectal cancer through IL-10 and TGF-ß.

The rate of colorectal cancer (CRC) is increasing. Adoptive immune cell therapy (ACT) is a research hotspot in CRC treatment, and the common adoptive cells are cytokine-induced killer cells (CIK). The problem of ACT is that some regulatory T cells (Treg) will affect the efficacy. Latent associated polypeptide (LAP)+CD4+T is a new Treg, and its immunosuppressive effect is much higher than that of traditional Tregs. This research mainly explored the influence of LAP+CD4+T cells on anti-tumor lethality of CIK cells, so as to fill this gap. The LAP+CD4+T CIK cells and LAP-CD4+T CIK cells were sorted by immunomagnetic beads. LAP+CD4+T cells were expanded in vitro, and high expression cytokine genes were screened by RT-qPCR. LAP+CD4+T and LAP-CD4+T CIK cells were co-cultured to test cyto-activity. Transplanted tumor models of CRC were established in nude mice, which were randomized into a control group (CG), CIK group, LAP (-) group, LAP (+) group, IL-10 siRNA group, and TGF-siRNA group, and the tumor growth in each group was observed. The research results revealed that interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) were highly expressed in LAP+CD4+T cells. LAP+CD4+T could effectively suppress CIK cell proliferation and activity. LAP-CD4+T could suppress IL-10 and TGF-ß, and inhibit CIK cell apoptosis, proliferation, and tumor growth, thus improving their anti-tumor lethality. LAP+CD4+T cells regulate the anti-tumor role of CIK cells in CRC through IL-10 and TGF-ß.

LigaSure hemorrhoidectomy versus the procedure for prolapse and hemorrhoids: A meta-analysis of randomized controlled trials.

BACKGROUND: LigaSure hemorrhoidectomy and the procedure for prolapse and hemorrhoids (PPH) are both relatively new treatments for managing symptomatic hemorrhoids. This review aimed to evaluate and compare their short-term outcomes. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the China National Knowledge Infrastructure database for randomized controlled trials comparing the LigaSure procedure and PPH published in any language from 1998 to October 2013. RESULTS: A total of 5 studies involving 397 participants were included in this review. Pooled analysis showed that the LigaSure procedure was associated with significantly lower recurrence rate [relative risk (RR) = 0.21, 95% confidence interval (CI): 0.06 to 0.72, P = .01] and significantly shorter operating time [mean difference (MD) = -6.39, 95% CI: -7.68 to -5.10, P < .001]. The analysis showed no significant difference in postoperative pain between the two techniques (MD = 0.55, 95% CI: -0.15 to 1.25, P = .12] or in time off work or away from normal activity [standard MD = 0.13, 95% CI: -1.80 to 2.06, P = .9]. The two techniques did not show significant differences in postoperative complications or other patient-related outcomes (P > .05). CONCLUSIONS: Our review indicates that both LigaSure hemorrhoidectomy and PPH are safe alternatives for the management of hemorrhoids. Available evidence suggests that the LigaSure technique is associated with shorter operating time and lower hemorrhoid recurrence rate, but these conclusions should be further confirmed in large, multicenter randomized controlled trials with long-term follow-up.

Screening and identification of hub gene and differential gene and mutation sequence analysis of related genes in colorectal cancer based on bioinformatics analysis.

Background: At present, the research of genomics is in ascendency, and using bioinformatics analysis methods to systematically explore the pathogenic genes and their regulatory mechanisms will play a great role in promoting the research of cancer. This study was to search The Cancer Genome Atlas (TCGA) database and extract inflammation-related non-coding RNA to construct a prognosis model of colon cancer and search for new immunotherapeutic targets. Methods: The transcriptome sequencing data and clinical data of 396 colon cancer patients were downloaded from TCGA database, and the inflammation-related non-coding RNA was obtained from the non-coding RNAs in Inflammation (ncRI) database. The prognostic model was constructed by univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression, and the optimal grouping threshold of risk score was determined by X-Tile software. The patients were risk stratified to further explore the differences in immune cell infiltration and biological function between the high- and low-risk groups. Results: The TCGA dataset of colon cancer was included to screen out 120 differentially expressed genes (DEGs) that overlapped in the 2 datasets, among which 29 genes were up-regulated and 91 genes were down-regulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the above 120 DEGs showed that proximal tubule sodium bicarbonate recovery, nitrogen metabolism, pancreatic fluid secretion, and PPAR signaling pathways were closely related to the occurrence of colon cancer. The expression of copper death-related genes was significantly correlated with the correlation coefficient of colon cancer (P<0.01). Gene Ontology analysis showed that the DEGs were mainly enriched in messenger RNA processing, RNA splicing, small G protein-mediated signal transduction, adhesion junction, mitochondrial matrix, mitochondrial protein complex, chromatin binding, small G protein binding, and Ras G protein binding, among others. KEGG analysis showed that the DEGs were enriched in the following pathways: herpes simplex virus type 1 infection, pathways of neurodegenerative diseases, Huntington's disease, prion disease, Parkinson's disease, the Ras signaling pathway, and so on. Conclusions: The key genes closely related to colon cancer were effectively screened by the bioinformatics method, which provided a theoretical basis for further study of its mechanism.

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

[Detection of transforming growth factor-ß1 in colorectal cancer and its clinical significance].

OBJECTIVE: To investigate the role of transforming growth factor ß1 (TGF-ß1) in patients with colorectal cancer. METHODS: Fresh peripheral blood were obtained from 50 patients (before surgery and at least one week after surgery) and 25 healthy donors in the morning. Fresh colorectal cancer tissues and the adjacent tissues (at least 5 cm from the tumor site) were obtained from patients undergoing tumor resection. The expression levels of TGF-ß1 in the blood and tissue specimens were determined using ELISA. RESULTS: The plasma levels of TGF-ß1 in patients with colorectal cancer were significantly higher than those in the healthy donors, and decreased after the surgery (P<0.05). The tumor tissues expressed higher levels of TGF-ß1 than the adjacent tissues from both CEA-negative and -positive patients. The plasma level of TGF-ß1 in the patients were positively correlated with the tumor size and clinical tumor stage (P<0.05). CONCLUSION: TGF-ß1 combined with CEA can provide important information for the diagnosis, prognostic assessment and prediction of recurrence in patients with colorectal cancer, and may provide new insights for anti-TGF-ß1-based tumor immune therapeutic strategies.

[Observation on clinical effect of ZHUANG medicine mediated thread moxibustion combined with medication for patients with ulcerative colitis].

OBJECTIVE: To observe the clinical effect and safety of Sulfasalazine (SASP) combined with ZHUANG medicine mediated thread moxibustion (ZMMTM) for patients with mild and moderate ulcerative colitis (UC). METHODS: A total of 46 UC patients were randomly and equally divided into moxibustion group (SASP combined with ZMMTM) and SASP medication group. Patients of both groups were treated by oral administration of SASP (1 g, tid) for six weeks. For patients of the moxibustion group, ZMMTM was applied to points Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4), and Dachangshu (BL 25), once a day, for 20 times. The therapeutic effect was assessed according to Schroeder and colleagues' method (1987), scores of Baron' s endoscope scale (0 - 9 scoring standards, 1964), 0 - 3 scoring standards of activity indexes (including 4 items of diarrhea, hemorrhage, mucosal appearance and doctors' evaluation), respectively. RESULTS: Of the two 32 UC patients in the medication and moxibustion groups, 6 and 9 had a complete remission in their symptoms, 6 and 7 experienced a remarkable improvement, 5 and 6 were effective, and 6 and 1 was invalid, with the effective rates being 73.91% and 95.65%, respectively. Following the treatment, both endoscopic score and activity index in the moxibustion group were significantly lower than those of the medication group (P < 0.05). CONCLUSION: ZMMTM combined with medication is significantly superior to simple medication in relieving clinical symptoms of mild and moderate UC patients.

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is the major cause for end-stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. METHODS: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta-analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. RESULTS: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11-1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25-2.21, P = 0.0004). In the sub-group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type-1. CONCLUSIONS: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.

[Observation on therapeutic effect of preoperational catgut implantation at acupoint for hemorrhoid operation-induced pain in patients].

OBJECTIVE: To assess the preemptive analgesia effect of catgut implantation in Chengshan (BL 57) area on hemorrhoid operation-induced pain and the security, so as to find a new method for easing post-operative pain of hemorrhoid. METHODS: A total of 120 cases of mixed hemorrhoids patients were randomly divided into the catgut implantation group and medication group (n=60). In implantation group, a piece of catgut was embedded into bilateral BL 57 acupoint area half an hour before surgery. Patients of the medication group were asked to orally take Tramadol Hydrochloride Capsules (100 mg) after the surgery. The pain score of mixed hemorrhoids patients was evaluated 5, 24, 48, 72 and 96 h after operation by using visual analogue scales (VAS). The complications, analgesics use and adverse reactions were recorded simultaneously. RESULTS: Comparison between two groups showed that the VAS scores of the catgut implantation group at 5, 24, 48, 72 and 96 h after operation were significantly lower than those of the medication group (P < 0.05). The incidence of complications of uroschesis and hydroncus, adverse reactions of nausea, vomiting and vertigo, and the number of patients using Sauteralgyl were significantly lower in the catgut implantation group than in the medication group (P < 0.05). CONCLUSION: Catgut implantation at BL 57 can effectively relieve the postoperative pain, reduce postoperative adverse reactions and complications in mixed hemorrhoids patients.

[Effect of electroacupuncture at Chengshan (BL 57) on postoperative pain of mixed hemorrhoids].

OBJECTIVE: To discuss the effect of electroacupuncture at Chengshan (BL 57) on postoperative pain of mixed hemorrhoids. METHODS: One hundred and twenty cases with postoperative pain of mixed hemorrhoids were divided into an electroacupuncture group (60 cases) and a medication group (60 cases) randomly. The disperse-dense wave in frequency of 2Hz/100Hz at Chengshan (BL 57) were used in the electroacupuncture group. Its first treatment was in 30 min after the operation, and then it was given once a day after hip bath in the morning. 2 tablets of Naproxen Sunstained Release Capsule were taken in 30 min after operation in the medication group, and then it was taken 2 tablets a day before dressing change. After 4 times of treatment, evaluate the changing condition of Visual Analogue Scale (VAS) at 5 h, 24 h, 48 h and 72 h after operation. RESULTS: The VAS at 5 h, 24 h, 48 h and 72 h after operation in the electroacupuncture group (6.78 +/- 2.12, 5.56 +/- 1.87, 4.34 +/- 2.23 and 3.15 +/- 2.11) were all lower than those in the medication group (7.56 +/- 2.01, 6.23 +/- 1.15, 5.57 +/- 2.21 and 4.34 +/- 2.12), and the difference was statistically significant (all P < 0.05). CONCLUSION: Electroacupuncture at Chengshan (BL 57) can reduce the postoperative pain of mixed hemorrhoids.