A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer.

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

[Pathogenesis of benign prostatic hyperplasia from the perspective of syndrome differentiation of viscera based on the neuro-endocrine-immune network].

According to the theory of traditional Chinese medicine (TCM), benign prostatic hyperplasia (BPH) belongs to the category of "Jing Long". Clinical management of BPH in TCM is root-aimed and kidney-targeted, in combination with the treatment of other viscera based on the syndrome differentiation of zang-fu organs. The neuro-endocrine-immune network of modern medicine is similar to the holistic concept of TCM. Based on the study of the neuro-endocrine-immune network, with kidney deficiency as the root of pathogenesis, and starting from the classification of viscera, this review elucidates the etiologic mechanisms of BHP from the perspective of Chinese and Western medicine and provides some reference for medication.

Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

Research progress of acupuncture and moxibustion for the enhanced synergism of chemotherapy. / é’ˆç¸ååŒåŒ–ç–—å®žçŽ°å¢žæ•ˆçš„ç ”ç©¶è¿›å±•.

The application of acupuncture and moxibustion in alleviating the adverse effects of chemotherapy drugs has been widely recognized at home and abroad, but the studies have been rarely summarized for the enhanced anti-tumor effect and its mechanism of acupuncture and moxibustion to synergize the chemotherapy drugs. This paper reviewed the clinical and basic studies on the synergism of chemotherapy with acupuncture and moxibustion in recent years. It was found that chemotherapy synergized with acupuncture and moxibustion can suppress cancer to a certain extent and improve the quality of life in patients. The effect mechanism of acupuncture and moxibustion combined with chemotherapy drugs is related to promoting tumor cell apoptosis, improving the immune and vascular microenvironment, and advancing chemotherapy drug enrichment on the affected area. It provides the evidences and ideas for enhancing the effect of chemotherapy by delivering acupuncture and moxibustion as an adjuvant therapy.

Evaluation of the therapeutic effect of Sacha inchi oil in atopic dermatitis mice.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition characterized by a multifaceted pathogenesis, which encompasses immune system signaling dysregulation, compromised skin barrier function, and genetic influencers. Sacha inchi (Plukenetia volubilis L.) oil (SIO) has demonstrated potent anti-inflammatory and antioxidant properties, however, the mechanism underlying the beneficial effects of SIO on AD remains unclear. This study aims to investigate the anti-AD effect of SIO and its possible molecular mechanism in mice with AD. The results demonstrated that SIO significantly reduced the degree of skin lesions and scratching, and improved the skin thickness and mast cell infiltration in AD mice. Furthermore, SIO significantly reduced the levels of immunoglobulin E, histamine and thymic stromal lymphopoietin in serum of AD mice. Additionally, it inhibited the expression of tumor necrosis factor-γ, interferon-γ, interleukin-2, interleukin-4, interleukin 1ß and other inflammatory cytokines in the lesions skin of mice. The Western blotting analysis revealed that SIO exhibited an upregulatory effect on the protein expression of filaggrin and loricrin, while concurrently exerting inhibitory effects on the protein expression and phosphorylation levels of P38, ERK, NF-κB, and IκBα within their respective signaling pathways. Consequently, it can be inferred that SIO exerts a significant anti-atopic dermatitis effect by modulating the P38, ERK, NF-κB, and IκBα signaling pathways. This study contributes to expand the research and development potential of SIO, and provides novel insights and potential therapeutic strategies for AD treatment.

Unlocking the anticancer activity of gambogic acid: a shift towards ferroptosis via a GSH/Trx dual antioxidant system.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in ferroptosis by regulating the cellular antioxidant response and maintaining redox balance. However, compounds that induce ferroptosis through dual antioxidant pathways based on Nrf2 have not been fully explored. In our study, we investigated the impact of Gambogic acid (GA) on MCF-7 cells and HepG2 cells in vitro. The cytotoxicity, colony formation assay and cell cycle assay demonstrated potent tumor-killing ability of GA, while its effect was rescued by ferroptosis inhibitors. Furthermore, RNA sequencing revealed the enrichment of ferroptosis pathway mediated by GA. In terms of ferroptosis indicators detection, evidences for GA were provided including reactive oxygen species (ROS) accumulation, alteration in mitochondrial membrane potential (MMP), disappearance of mitochondrial cristae, lipid peroxidation induction, malondialdehyde (MDA) accumulation promotion, iron ion accumulation as well as glutathione (GSH)/thioredoxin (Trx) depletion. Notably, Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) successfully rescued GA-induced MDA accumulation. In terms of mechanism, Nrf2 was found to play a pivotal role in GA-induced ferroptosis by inducing protein alterations through the iron metabolism pathway and GSH/Trx dual antioxidant pathway. Furthermore, GA exerted good antitumor activity in vivo through GSH/Trx dual antioxidant pathway, and Fer-1 significantly attenuated its efficacy. In conclusion, our findings first provided new evidence for GA as an inducer of ferroptosis, and Nrf2-mediated GSH/Trx dual antioxidant system played an important role in GA-induced ferroptosis.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Excess Mortality for Femoral Intertrochanteric Fracture Patients Aged 50 Years and Older Treated Surgically and Conservatively in Tianjin, China: A Cohort Study.

OBJECTIVE: Intertrochanteric fracture is one type of hip fracture, which is the most serious consequence of osteoporosis. Along with the growing elderly population, intertrochanteric fracture is expected to rise increasingly. The aim of this study was to assess excess mortality after intertrochanteric fractures and to identify the predictors of long-term mortality by therapy among patients aged 50 years and older in Tianjin. METHODS: This is a retrospective cohort study on mortality for 3029 patients aged 50 years and older in Tianjin experiencing an intertrochanteric fracture between December 26, 2014 and December 31, 2018. Data were from Tianjin Hospital Hip Fracture (THHF) cohort. Follow-up period was until March 31, 2022. Mortality, excess mortality, and comorbidities were analyzed and stratified by therapy and gender. Time dependent Cox models were performed to estimate the effects of the variables. RESULTS: Absolute mortality for all the patients was 5.90% at 3 months, 12.55% at 12 months, 19.92% at 24 months and 27.28% at 36 months. Absolute mortality for surgical group was 1.57% at 3 months, 4.77% at 12 months, 8.49% at 24 months and 12.07% at 36 months, significantly lower than conservative group: 10.50% at 3 months, 20.73% at 12 months, 31.96% at 24 months and 43.04% at 36 months. We found a substantially lower mortality (hazard ratio [HR] 0.34, 95% confidence internal, [CI]: 0.23-0.52, p = 0.000) among patients undergoing surgical therapy than those undergoing conservative therapy, even when controlled for gender, age, the length of hospital stay, and all the comorbidities. Female patients (HR 0.68, 95% CI: 0.58-0.79, p = 0.000) were less likely to die than male patients after an intertrochanteric fracture. Patients treated by the two methods were both found to have excess mortality rates compared to the general population, although in different levels. The excess mortality rates for patients in the conservative therapy group were 14.46% in males and 17.93% in females, while in the surgical therapy group, 2.78% in females and 4.37% in males. The comorbidities moderate or severe renal disease (HR 2.19, 95% CI: 1.61-2.98, p = 0.000), metastatic solid tumor (HR 6.35, 95% CI: 1.56-25.85, p = 0.010), hypoproteinemia (HR 1.22, 95% CI: 1.01-1.47, p = 0.034), and older age (HR 1.89, 95% CI: 1.73-2.08, p = 0.000) were also risk factors on mortality. A worse-case analysis for the primary outcome were performed as sensitivity analysis and it was consistent with the original conclusion. CONCLUSION: Intertrochanteric factures for people aged 50 years older were found to have excess mortality compared to the general population in Tianjin city, and preventing the fractures in the hip for elderly people was imperative. After controlling tfor comorbidities and age, female gender and surgical therapy were protective factors for the death after fractures, which could provide strong evidence for patients and surgeons to make decisions.

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.

BACKGROUND: Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. METHODS: The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. RESULTS: CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. CONCLUSIONS: Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Relationship between inferior mesenteric artery diameter and rectal cancer.

Introduction: A dilated inferior mesenteric vein has been reported in rectal cancer patients. However, no study has yet reported inferior mesenteric artery (IMA) enlargement in rectal cancer. We aimed to assess the relationship between the IMA diameter and rectal cancer. Material and methods: Patients diagnosed with rectal cancer and a control group of 42 patients in our hospital from July 2017 to June 2019 were evaluated. The IMA diameter was independently measured by two observers on axial computed tomography images. Results: The mean IMA diameter was wider in rectal cancer patients (2.49 ±0.53 mm) than in the control group (2.20 ±0.47 mm, p < 0.001). The IMA diameter of patients with stage I, stage II, stage III, and stage IV cancers was 2.24 ±0.36 mm, 2.45 ±0.39 mm, 2.80 ±0.55 mm, and 2.85 ±0.51 mm, respectively (p < 0.001). The IMA diameter correlated positively and moderately with TNM stage (r = 0.519, p < 0.001). The IMA diameter of patients with T1, T2, T3, and T4 tumors was 2.18 ±0.31 mm, 2.39 ±0.50 mm, 2.55 ±0.48 mm, and 2.73 ±0.51 mm, respectively (p < 0.001). The IMA diameter also correlated positively and moderately with T stage (r = 0.457, p < 0.001). The IMA diameter of patients with N0, N1, and N2 tumors was 2.37 ±0.39 mm, 2.83 ±0.60 mm, and 2.71 ±0.40 mm, respectively (p < 0.001); however, the IMA diameter did not correlate with N stage (r = 0.166, p = 0.077). Patients with M1 tumors had a wider IMA diameter than patients with M0 tumors (p = 0.011). Conclusions: The IMA in rectal cancer patients enlarges as the TNM stage gets higher. The IMA diameter can be accepted as a possibly important marker for the staging of rectal cancer.

Changes in intracellular calcium concentration level accompany age-related inhibitions of long-term potentiation in hippocampus induced by extremely low frequency electromagnetic fields.

Extremely low frequency electromagnetic fields (ELF-EMFs) have received increasing attention and in-depth research due to their ability to affect learning and memory functions. However, its regulation and intrinsic mechanism at different ages in early developmental stages remains unclear. In this article, the regulation of 15 Hz/2 mT ELF-EMFs on long-term potentiation (LTP) persistence in the hippocampal CA1 region of Sprague-Dawley (SD) rats at early developmental stages (8-, 15-, 22-, and 29-day-old) are investigated by electrophysiological techniques. The results show that ELF-EMFs differentially inhibit LTP persistence due to age difference, and the younger the age, the more significant the inhibitory effect. Second, the inhibitory effect of ELF-EMFs on LTP persistence disappeared after the addition of 2-aminoethoxydiphenyl borate (2-APB) to block inositol-1,4,5-trisphosphate receptors (IP3 Rs) localized to intracellular calcium stores to reduce the intracellular calcium concentration ([Ca2+ ]i ), proving that the LTP persistence regulated by ELF-EMFs is associated with the IP3 Rs-mediated intracellular calcium stores. Finally, the level of [Ca2+ ]i was intervened by adjusting the extracellular calcium concentration([Ca2+ ]e ). Interestingly, the inhibitory effect of ELF-EMFs on LTP persistence in the 15-day-old group disappeared by increasing [Ca2+ ]e , whereas the inhibitory effect of ELF-EMFs on LTP persistence in the 29-day-old group appeared by decreasing [Ca2+ ]e . Our findings reveal the underlying mechanism of the effect of ELF-EMFs on synaptic plasticity in hippocampal CA1 area at early developmental stages and provide new insights into more rational application and protection of ELF-EMFs.

Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Probiotic fermentation is a mild and safe biological method to boost the performance of herbs. Portulaca oleracea L. (PO), with folklore records of purgative, anti-dermatological and anti-epidemic effects, has been demonstrated to possess anti-inflammatory, immunomodulatory, and antioxidant properties. However, the potential of PO for the treatment of atopic dermatitis (AD) has not been sufficiently explored. AIM OF STUDY: This study aimed to evaluate the therapeutic benefits of PO and fermented Portulaca oleracea L. (FPO) and explore their intrinsic mechanisms. METHODS: By utilizing 2,4-dinitrofluorobenzene-induced AD mice as a model, the histopathology of the lesions was observed using H&E and toluidine blue staining methods; the levels of immunoglobulin E (Ig E), histamine (HIS), and thymic stromal lymphopoietin (TSLP) in serum were measured using ELISA, whereas, the expression of inflammatory cytokines in skin lesion was measured using ELISA and immunohistochemistry experiments. The expression of tumor necrosis factor-α (TNF-α), IKKα, NF-κB mRNA was measured using qPCR; and the expression of TNF-α、p-IKKα, p-IκBα, p-NF-κB was measured using western blotting. RESULTS: Both 20 mg/mL PO and FPO alleviated mast cell infiltration and lesion pathology, reduced serum levels of Ig E, HIS and TSLP, down-regulated the expression of AD-related inflammatory cytokines, such as, TNF-α, interferon-γ, and interleukin-4, and increased filaggrin expression. Furthermore, they inhibited the expression of TNF-α, IKKα, and NF-κB genes and TNF-α, p-IKKα, p-NF-κB and p-IκBα proteins associated with the NF-κB signaling pathway. CONCLUSIONS: PO and FPO has a positive therapeutic potential on AD, indicating that it may be employed as alternative therapies for AD.

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma.

NTRK fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in NTRK-positive solid tumors. Although some NTRK fusion partners have been identified in thyroid cancer, the spectrum of NTRK fusion is not fully characterized. In this study, a dual NTRK3 fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between NTRK3 exon 13 and AJUBA exon 2, co-existing with a known in-frame fusion between ETV6 exon 4 and NTRK3 exon 14. The dual NTRK3 fusion was validated by Sanger sequencing and fluorescence in situ hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer. These findings extend the spectrum of translocation partners in NTRK3 fusion, and the effect of dual NTRK3 fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.

Peripheral blood T-lymphocyte subsets are potential biomarkers of disease severity and clinical outcomes in patients with ulcerative colitis: a retrospective study.

BACKGROUND: Ulcerative colitis (UC) is considered an immune-mediated disease. The disorder of T-lymphocyte subsets plays an important role in the pathogenesis of UC. The aim of this study was to evaluate the significance of peripheral blood T-lymphocyte subsets in assessing disease severity and predicting clinical outcomes in UC patients. METHODS: The retrospective case-control study was performed in 116 UC patients with active disease and 90 healthy controls (HC). The UC patients included were followed up for 180 days. Analyses of t-test, Spearman's correlation coefficient, multivariable Cox regression analysis, receiver operating characteristic (ROC) curves and cumulative survival analysis were done. RESULTS: The UC patients had lower proportions of CD4+T cells (42.85%±9.77% vs 45.71%±7.94%, P=0.021) and higher proportion of CD8+T cells (27.88%±8.86% vs 25.00%±6.47%, P=0.008) than HC. The severely active UC patients had higher proportion of CD3+HLA-DR+ T cells (8.83%±6.55% vs 2.80%±1.55%, P<0.001; 8.83%±6.55% vs 4.06%±5.01%, P<0.001) and CD8+T cells (31.35%±8.49% vs 26.98%±7.98%, P=0.029; 31.35%±8.49% vs 25.46%±9.15%, P=0.003) than mild and moderate group, whereas lower proportion of CD4+CD25+T cells (2.86%±1.35% vs 3.46%±1.07%, P=0.034) than mild group and CD4+T cells (40.40%±9.36% vs 44.73%±10.39%, P=0.049) than moderate group. The area under the curve (AUC) of CD3+HLA-DR+ T cells for assessing severely active UC was 0.885, with the cut-off value of 5.33%. The sensitivity was 76.32% and specificity was 89.74%. The combination of CD3+HLA-DR+ T cells and CRP had stronger assessment value with AUC of 0.929. The AUC of CD8+T cells, CD4+/CD8+ ratio and CD4+CD25+T cells for assessing disease severity was 0.677, 0.669 and 0.631 respectively. Within the 180 days follow-up, 24 patients (20.69%) had UC-related readmission or surgery, with higher proportion of CD3+HLA-DR+ T cells (10.66%±9.52% vs 3.88%±2.56%, P=0.003) and CD8+T cells (31.19%±10.59% vs 27.01%±8.20%, P=0.039) than those without readmission and surgery. The proportion of CD3+HLA-DR+ T cells was the independent predictor of UC-related readmission or surgery (HR=1.109, P=0.002). The AUC of CD3+HLA-DR+ T cells for predicting readmission or surgery was 0.796 with the cut-off value of 5.38%. UC patients with CD3+HLA-DR+T cells proportion>5.38% had a shorter time to readmission or surgery (log-rank test, P<0.001). CONCLUSIONS: The combination of CD3+HLA-DR+T cells and CRP may be potential biomarker of disease severity in UC patients. The high proportion of CD3+HLA-DR+T cells may be associated with an increased risk of readmission or surgery in UC patients.

Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.

Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.

Causal association between colorectal cancer and Alzheimer's disease: a bidirectional two-sample mendelian randomization study.

Background: Colorectal cancer and Alzheimer's disease are both common life-threatening diseases in the elderly population. Some studies suggest a possible inverse relationship between colorectal cancer and Alzheimer's disease, but real-world research is subject to many biases. We hope to clarify the causal relationship between the two through a bidirectional two-sample Mendelian randomization study. Methods: In our study, we used genetic summary data from large-scale genome-wide association studies to investigate the relationship between colorectal cancer and Alzheimer's disease. Our primary analysis employed the inverse-variance weighted method and we also used complementary techniques, including MR-Egger, weighted median estimator, and Maximum likelihood. We applied simex adjustment to the MR-Egger results. We also utilized the MRlap package to detect potential sample overlap and its impact on the bias of the results. In addition, we performed several sensitivity and heterogeneity analyses, to ensure the reliability of our results. Results: The combined effect size results of the inverse-variance weighted method indicate that colorectal cancer may decrease the incidence of Alzheimer's disease, with an odds ratio (OR) of 0.846 (95% CI: 0.762-0.929). Similar results were observed using other methods such as MR-Egger, weighted median estimator, and Maximum likelihood. On the other hand, Alzheimer's disease may slightly increase the incidence of colorectal cancer, with an OR of 1.014 (95% CI: 1.001-1.027). However, the results of one subgroup were not significant, and the results from MRlap indicated that sample overlap introduced bias into the results. Therefore, the results of the reverse validation are not reliable. The F-statistic for all SNPs was greater than 20. Four SNPs related to the outcome were excluded using Phenoscanner website but the adjustment did not affect the overall direction of the results. The results of these statistics were further validated by MR-PRESSO, funnel plots, leave-one-out analyses, Cochran's Q, demonstrating the reliability of the findings. Conclusion: According to the findings of this Mendelian randomization study, there appears to be a causal association between colorectal cancer and Alzheimer's disease. These results could have important implications for clinical practice in terms of how colorectal cancer and Alzheimer's disease are treated. To better understand the relationship between these two diseases, more research and screening are needed in clinical settings.

Prognostic Biomarkers Identification in Esophageal Cancer Based on WGCNA and Single-Cell Analysis.

Background: Esophageal cancer is one of the most common cancers worldwide. Dysregulation of genes plays an important role in cancer. In this study, we aimed to investigate the prognostic biomarkers in esophageal cancer based on comprehensive bioinformatics analysis including WGCNA and single cell analysis. Methods: RNA sequencing data of esophageal cancer was downloaded from GSE75241 dataset in the GEO database. We also selected esophageal cancer patients from public databases (Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA)). WGCNA was used to construct a scale-free coexpression network of genes. Multifactor Cox analysis model was constructed as the prognostic model in esophageal cancer. Furthermore, single-cell gene analysis was used to discover the mechanism of hub genes in esophageal cancer. Results: WGCNA discovered 182 genes for further analysis. Among 182 genes, four genes including ANGPT2, VCAN, MS4A4A, and FOS had significant prognostic value in esophageal cancer. In single cell analysis, seven types of cells subsets were distinguished including T cells, B cells, NK cells, monocytes, macrophages, DCs, neutrophils. The expression of four hub genes (ANGPT2, VCAN, MS4A4A, and FOS) in inflammatory cell subsets was evaluated, respectively. Hub genes were correlated with inflammatory cells in esophageal cancer. In addition, the subgroups of specific inflammatory cells such as macrophages, monocytes, and DCs were analyzed to identify the function of hub genes, either. Hub genes were correlated with differentiation of inflammatory cells including monocytes, macrophages, and DCs in tumor environment. Conclusions: We identified specific hub genes correlated with prognosis of esophageal cancer. These hub genes play critical roles by regulating inflammatory cells status in esophageal cancer.

Development of one-step multiplex RT-PCR assay for rapid simultaneous detection of five RNA viruses and Acidovorax citrulli in major cucurbitaceous crops in China.

Cucurbitaceous fruits and vegetables are important crops. Viral and bacterial diseases cause substantial economic losses to cucurbit crops globally. For rapid detection of these pathogens and improved disease control, a one-step multiplex reverse-transcription polymerase chain reaction (mRT-PCR) system was created. This method allowed for the concurrent detection of Tobacco mosaic virus (TMV), Zucchini yellow mosaic virus (ZYMV), Watermelon mosaic virus (WMV), Cucumber green mottle mosaic virus (CGMMV), Cucumber mosaic virus (CMV), and Acidovorax citrulli. Five pairs of specific primers were created according to the conserved regions around the coat protein (CP) genes of each virus, and one pair was based on the A. citrulli internal transcribed spacer (ITS). To limit false negatives, one pair of primers, created based on the Transcriptional elongation factor 1-α (EF1-α) from the major cucurbitaceous crop species, was put into the mRT-PCR reaction system. Primer concentrations, annealing temperature, extension time, and amplification cycles were optimized. Anticipated fragments of 152 bp (TMV), 205 bp (ZYMV), 318 bp (WMV), 419 bp (CGMMV), 529 bp (CMV), 662 bp (A. citrulli), and 821 bp (EF1-α) were amplified by the multiplex RT-PCR system, and their origin was established via DNA sequencing. This method was successfully used to examine field-collected seed samples of cucurbitaceous crops from China. The results demonstrated that the one-step mRT-PCR technique is a quick, efficient, and sensitive assay for the concurrent detection of six pathogens of cucurbits. It provides a method for monitoring and preventing these diseases.

First Report of Bacterial Canker of Pecan Caused by Pseudomonas syringae pv. syringae in China.

Pecan (Carya illinoinensis) is a world-famous nut tree that is widely cultivated in China, especially in Jiangsu Province (Zhang et al. 2015). In April 2022, cankers on trunks were recorded in pecan (cv. Pawnee) fields located in Taizhou (32°27'58″ N, 120°0'49″ E), Jiangsu. Cankers on the trunks resulted in wilt of the plants. Usually, the color of infected bark on the trunk became darker than the healty bark. When the outer bark was peeled away, the inner tissues were water-soaked, often with reddish streaks. In the surveyed orchards, disease incidence ranged from 10 to 20% among young saplings (about 200 three-year-old trees). While no fungal mycelium or spores were found in the diseased areas by microscope, bacterial colonies were isolated by surface-sterilizing small fragments (25 mm2) of symptomatic tissue in 0.5% NaOCl, rinsing the sections twice in sterilized water, and then streaking them on Luria-Bertani (LB) plates. More than 20 bacterial isolates were obtained and all isolates induced a hypersensitive response on Nicotiana tabacum. All isolates were fluorescent on King's medium B, and were gram-negative based on lysis by KOH. Isolates were positive for levan formation, negative for oxidase and arginine dihydrolase, and did not cause soft rot on potato slices. Based on above information, the isolates thus belonged to Lelliot's LOPAT group 1, P. syringae (Lelliott and Stead 1988). The 16S rRNA sequences of five representative isolates (accession numbers OP175939-OP175943) were amplified by PCR, sequenced, and compared with the NCBI GenBank database (Weisburg et al. 1991; Sarkar and Guttman 2004), finding a 99.92% genetic similarity with a previously reported 16S rRNA sequence of a Pseudomonas syringae pv. syringae (Pss) isolate (accession numbers NW389777). Additional housekeeping genes gap1(accession numbers OP186937-OP186941), rpoD (accession numbers OP186952-OP186956), gyrB (accession numbers OP186947-OP186951), and gltA (accession numbers OP186942-OP186946) were PCR-amplified and sequenced as reported by Hwang et al. (2005), followed by multilocus sequence typing analysis (MLSA). Molecular phylogenetic trees (MEGA vesion 6.0, maximum likelihood with Jukes-Cantor model, 1,000 bootstraps) were generated based on each of these five DNA regions and revealed that all five isolates were clustered together with the strains in P. syringae genomospecies 2, and grouped these isolates with Pss in the PAMDB database (Hwang et al. 2005). As a result, these isolates were identified as Pss. Pathogenicity on pecan (cv. Pawnee) was confirmed by cutting the trunks of two-year-old pecan trees with sterilized blades dipped in cell suspensions containing 107 CFU/ml of each isolate. Plants inoculated in a similar manner with sterile water served as negative controls. The inoculated plants were incubated in a greenhouse maintained at 25°C and 80% relative humidity. After 7 to 8 days, all inoculated plants showed the symptoms of necrosis previously described for the original field plants, while the control plants did not show symptoms. The bacteria reisolated from the inoculated plants were identified as Pss using the LOPAT tests. These results and the sequence analysis of the 16S rRNA and four housekeeping genes described above, fulfilled Koch's postulates. No target bacteria were isolated from the control plants. To our knowledge, this is the first report of Pseudomonas syringae pv. syringaecausing bacterial canker of pecan worldwide. The identification of this pathogen will allow the study of strategies for managing the disease. References: Hwang, M. S., et al. 2005. Applied and Environmental Microbiology, 71:5182-5191. Lelliott, R. A., and Stead, D. E. 1988. Blackwell Scientific, Sussex, UK. Sarkar, S. F., and Guttman, D. S. 2004. Applied and Environmental Microbiology, 70:1999. Weisburg, W. G., et al. 1991. Journal of Bacteriology, 173: 697. Zhang, R., et al. 2015. Scientia Horticulturae, 197: 719-727. The author(s) declare no conflict of interest. Keywords: Carya illinoinensis, Pseudomonas syringae, Canker, Identification †Indicates the corresponding author.Y. Q. Zhao; zhaoyuqiang123@126.com.