BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Gastric cancer is one of the major types of cancer threatening human health worldwide. Its pathogenesis has not been fully elucidated, and patients are often diagnosed at an advanced stage. The oral cavity is the second largest microbial pool after the intestine in the human body, and thus the relationship between oral bacteria and human health is attracting increasing interest. Oral bacteria are closely related to gastric cancer and potentially serve as noninvasive diagnostic screening biomarkers for the disease. Imbalance in and displacement of these bacteria can promote the occurrence and development of gastric cancer. Hence, this article reviews the association between oral bacteria and gastric cancer, aiming to provide a basis for further elucidating the pathogenesis of gastric cancer and screening it early through noninvasive methods and serve as a reference for subsequent related research.

Objective:To evaluate the influence of Helicobacter pylori ( H. pylori) infection on anxiety and depression in patients with chronic gastritis. Methods:From December 1 2020 to June 30 2021, 387 patients with chronic gastritis who visited the outpatient Department of Gastroenterology, the First Hospital Affiliated to Air Force Medical University were continuously recruited. According to the status of current H. pylori infection, the patients were divided into H. pylori uninfected group and H. pylori infected group. The general demographic information of patients was collected. Hamilton anxiety scale, Hamilton depression rating scale-24, Pittsburgh sleep quality index (PSQI) and gastrointestinal symptom rating scale (GSRS) were filled in. The detection rates of anxiety and depression were compared between the H. pylori uninfected group and the H. pylori infected group according to demographic characteristics. Chi-square test and multiple logistic regression analysis were used for statistical analysis. Results:Finally, 360 patients with chronic gastritis were enrolled, including 200 patients in H. pylori uninfected group and 160 patients in H. pylori infected group. The detection rates of anxiety and depression of the H. pylori infected group were both higher than those of the H. pylori uninfected group (48.1%, 77/160 vs. 30.0%, 60/200; 25.0%, 40/160 vs. 12.5%, 25/200), and the differences were statistically significant ( χ2=12.39 and 9.39, P<0.001 and=0.002). The detection rate of anxiety of male patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (45.1%, 32/71 vs. 24.5%, 27/110); the detection rate of depression of female patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (30.3%, 27/89 vs. 11.1%, 10/90), and the differences were statistically significant ( χ2=8.27 and 10.09, P=0.004 and 0.001). The detection rates of anxiety and depression of patients less than 48 years old in the H. pylori infected group were both higher than those in the H. pylori uninfected group (46.2%, 37/80 vs. 21.9%, 21/96; 20.0%, 16/80 vs. 7.3%, 7/96), and the differences were statistically significant ( χ2=11.73 and 6.20, P=0.001 and 0.013). The detection rates of anxiety and depression of the patients with high school education and below in the H. pylori infected group were higher than those in the H. pylori uninfected group (56.5%, 48/85 vs. 31.7%, 38/120; 32.9%, 28/85 vs. 14.2%, 17/120), and the differences were statistically significant ( χ2=12.57 and 10.24, P<0.001 and =0.001). The results of multivariate analysis showed that H. pylori infection, history of hypertension, PSQI score ≥8, GSRS score ≥7, chronic superficial gastritis and chronic atrophic gastritis were independent risk factors of anxiety in patients with chronic gastritis( P<0.001, =0.013, =0.001, <0.001, =0.036, =0.021), and the risk of anxiety of patients with H. pylori infection was 2.509 times as much as that in uninfected patients (95% confidence interval 1.512 to 4.163). H. pylori infection, PSQI score ≥8, GSRS score≥7, and having overnight dish ≥3 times per week all were independent risk factors of depression in patients with chronic gastritis( P=0.004, =0.002, <0.001, =0.001). The risk of depression in patients with H. pylori infection was 2.563 times as much as that in uninfected patients (95% confidence interval 1.356 to 4.846). Conclusion:H. pylori infection is correlated to anxiety and depression in patients with chronic gastritis, and it is an independent risk factor of anxiety and depression in patients with chronic gastritis.

Humans ; Bile Reflux/complications* ; Cross-Sectional Studies ; Risk Factors ; Gastric Mucosa

BACKGROUND: With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS: This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS: A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.
Humans ; Amoxicillin/therapeutic use* ; Helicobacter pylori ; Anti-Bacterial Agents ; Clarithromycin/therapeutic use* ; Rabeprazole/therapeutic use* ; Berberine/therapeutic use* ; Bismuth ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Background:Duodenal neuroendocrine tumors(DNETs)are rare tumors,their disease characteristics are currently not well understood.At present,there are no research data on non-ampullary region DNETs in China.Aims:To analyze the clinical characteristics of patients with non-ampullary region DNETs in order to guide clinical practice.Methods:The clinical data ofnon-ampullary region DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Using the method of retrospective study,analyze the clinical characteristics of patients.Results:Twenty-two non-ampullary region DNETs patients were screened.Among them,8(36.4%)patients'tumor diameter<2 cm,14(63.6%)patients'tumor diameter≥2 cm.When non-ampullary region DNETs were diagnosed,the main clinical symptoms were abdominal distension(59.1%),followed by abdominal pain(41.0%).When diagnosed,half(50%)of patients with non-ampullary DNETs with tumor diameter<2 cm have no clinical symptoms.The clinical symptoms of non-ampullary DNETs patients with tumor diameter≥2 cm were mainly abdominal distension(85.7%),followed by abdominal pain(57.1%),and a few(14.3%)patients had no clinical symptoms.After diagnosed,the survival time of patients with tumor diameter<2 cm was longer than that of patients with tumor diameter≥2 cm(P=0.048).By the end of follow-up,the median survival time of patients with non-ampullary region DNETs was 451.0 months.Six patients had died,all of their tumor diameter were≥2 cm at diagnosis.Three of patients who died had stage Ⅳ at diagnosis,and all had liver metastases.Patients with tumor diameter<2 cm underwent surgical treatment and all survived after surgery.Conclusions:Abdominal distension is the main clinical manifestation of non-ampullary region DNETs patients,and the organ that is more likely to metastasize is the liver.The survival time of patients with non-ampullary region DNETs with tumor diameter<2 cm was longer than that of patients with tumor diameter≥2 cm.

Spasmolytic polypeptide expressing metaplasia(SPEM)is a kind of metaplasia of gastric mucosa.There are three hypotheses of its origin,including chief cell transdifferentiation,stem cell differentiation,and pre-SPEM hypotheses.Currently,animal models are commonly used for the mechanism research.According to results of the researches,SPEM plays a role in the repair of gastric mucosal damage,Helicobacter pylori infection and the development of gastric cancer.This paper provides an overview of the above issues and the multiple ways of modeling the SPEM.

Background:Therapeutic drug monitoring(TDM)has emerged as the important method for managing loss of response to infliximab.The effect of reactive and proactive TDM on clinical outcomes in inflammatory bowel disease(IBD)is uncertain.Aims:To evaluate the effect of proactive and reactive TDM of infliximab on the prognosis of patients with IBD.Methods:Clinical data of 99 IBD patients treated with IFX from January 2017 to October 2021 at the First Affiliated Hospital of Air Force Military Medical University were retrospectively analyzed,including 34 patients with proactive TDM and 65 patients with reactive TDM.The rate of treatment failure,IBD-related surgery or hospitalization were compared between the two groups.Logistic regression analysis was used to determine the independent risk factors of treatment failure.Results:The median follow-up of the patients was 21(13,32)months.The rate of treatment failure,IBD-related hospitalization rate of proactive TDM group were significantly lower than those of reactive TDM group(P<0.05),however,no significant difference in IBD-related surgery rate was found between two groups(P=0.081).Univariate analysis showed that ileocolonic resection before TDM,antibodies to infliximab(ATI)and reactive TDM might be correlated with treatment failure(P<0.05).Logistic regression analysis showed that reactive TDM(OR=5.829,95%CI:1.070-31.754,P=0.042)was the risk factor of treatment failure,and ileocolonic resection before TDM(OR=0.119,95%CI:0.019-0.736,P=0.022)was the protective factor of treatment failure.Conclusions:Compared with reactive TDM group,proactive TDM can significantly decrease the rate of treatment failure and IBD-related hospitalization rate.Reactive TDM is the risk factor of treatment failure,and ileocolonic resection before TDM is the protective factor of treatment failure.

Objective:To investigate the relationship between common functional gastrointestinal diseases symptoms with psychological factors, diet and lifestyles by using the network analysis method which has achieved great success in the field of psychology in recent years.Method:A questionnaire survey was conducted in two military units using the cluster sampling method during July 2020, and a total of 1 805 subjects were included. Functional gastrointestinal disease symptoms were evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). The state, trait anxiety scale and stress response scale were used to evaluate the mental and psychological state by self-evaluation. R was used to build the network and calculate statistical parameters.Results:1 486 of the 1 805 subjects (82.3%) had experienced functional gastrointestinal diseases symptoms within 2 weeks, but most of them were mild. Network analysis shows that there was a strong interaction between digestive system symptoms with different clinical manifestations (Spearman coefficient ranges 0.31-0.56). There was a clear relationship between functional gastrointestinal symptoms and mental and psychological factors (Spearman coefficient ranges 0.16-0.27), but there was no clear interaction with diet, age, education level, body mass index, etc. Functional gastrointestinal diseases symptoms were connected with mental and psychological factors through two nodes: stress and indigestion. The stability coefficient of node strength correlation was 0.75, indicating that the network was stable.Conclusions:The current study revealed the network structure and features of functional gastrointestinal diseases symptoms with mental and psychological factors. The key linking nodes provided potential interfering target for controlling functional gastrointestinal symptoms related to mental and psychological factors.