Objective:To investigate the correlation between serum prostaglandin E2 (PGE2), heat-shock protein 70 (HSP-70) and the severity of bleeding in patients with peptic ulcer bleeding (PUB).Methods:A total of 122 patients with peptic ulcer (PU) admitted to Chang'an Hospital from March 2021 to March 2024 were retrospectively collected and divided into simple PU group (50 cases) and PUB group (72 cases) according to whether PUB occurred. Serum levels of PGE2 and HSP-70 were determined by enzyme-linked immunosorbent assay (ELISA). Spearman test was used to analyze the correlation between serum PGE2, HSP-70 levels and bleeding severity in PUB patients. Logistic regression was used to analyze the risk factors of PUB, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PGE2 and HSP-70 levels on the bleeding degree of PUB patients.Results:The proportion of non-steroidal anti-inflammatory drugsnon-ster (NSAID) used and Helicobacter pylori (Hp) infection, thromboplastin time (APTT) and prothrombin time (PT) in the PUB group were higher than those in the PU group: 42.00%(21/50) vs. 25.00%(18/72), 36.00%(18/50) vs. 58.33%(42/72), (28.78 ± 3.24) s vs. (26.72 ± 3.89) s, (13.14 ± 2.56) s vs. (11.26 ± 2.15) s, and the serum levels of PGE2 and HSP-70 were lower than those in the PU group: (174.25 ± 18.21) ng/L vs. (236.44 ± 24.52) ng/L, (0.78 ± 0.22) μg/L vs. (1.24 ± 0.38) μg/L, there were statistical significances ( P<0.05). The serum levels of PGE2 and HSP-70 in PUB patients decreased gradually with the severity of hemorrhage ( P<0.05). Spearman test showed that serum PGE2 and HSP-70 levels were negatively correlated with the severity of bleeding in PUB patients ( r = - 0.720, - 0.586, P<0.01). Logistic regression analysis showed that serum PGE2 and HSP-70 levels were protective factors for PUB ( P<0.05), while NSAID used, Hp infection, APTT and PT were risk factors for PUB ( P<0.05). ROC curve analysis results showed that the area under the curve of serum PGE2 and HSP-70 combined to predict the severity of bleeding in PUB patients was 0.935, which was higher than that predicted by the two indexes alone. Conclusions:The expression of serum PGE2 and HSP-70 are down regulated in PUB patients, and have correlated with the severity of bleeding. The joint detection of two indicators is more conductive to predicting the degree of bleeding in PUB patients.

Objective To establish a brucellosis monitoring and testing technique applicable for the rapid field screening of natural epidemic diseases.Methods A rapid testing technique for Brucella was developed based on a double-antibody sandwich testing model using gradient-variant quantum dots as fluorescent tracers.The sensitivity,linearity,precision,and specificity of the technique were evaluated using suspensions of standard Brucella strains.Methodological comparisons across different sample types were conducted to assess the consistency of the test results.Results The gradient-variant quantum dots detection method was evaluated with standard Brucella strains,exhibiting a sensitivity of 1×103 CFU/mL and a linear correlation coefficient(r)of 0.994(95%CI,0.933-1.055).The maximum coefficient of variation was 12.94%in repeated tests,showing good specificity.A comparative assessment of 305 clinical samples was conducted using the Brucella gradient-variant quantum dots detection method,the Rose Bengal plate agglutination test(RBT),and the serum agglutination test(SAT),yielding a Kappa value of 0.95,indicating almost perfect agreement.Additionally,a comparative assessment of 110 environmental samples collected on-site was conducted using the Brucella gradient-variant quantum dots detection method and quantitative real-time PCR(qPCR).The Kappa values for aerosol collection fluid,surface wipes,and wool samples were all above 0.83,demonstrating near-perfect agreement.For fecal and soil samples,the Kappa values were above 0.62,indicating substantial agreement.Conclusion The Brucella detection method based on gradient-variant quantum dots technology is simple and can be conducted rapidly.The detection method demonstrates high sensitivity,linearity,precision,and specificity.It shows consistent performance in clinical sample testing.It is well-suited for field rapid screening of natural epidemic diseases in field settings and shows good application prospects in the monitoring,prevention,and rapid detection of zoonotic diseases.

Objective:To investigate the correlation between serum prostaglandin E2 (PGE2), heat-shock protein 70 (HSP-70) and the severity of bleeding in patients with peptic ulcer bleeding (PUB).Methods:A total of 122 patients with peptic ulcer (PU) admitted to Chang'an Hospital from March 2021 to March 2024 were retrospectively collected and divided into simple PU group (50 cases) and PUB group (72 cases) according to whether PUB occurred. Serum levels of PGE2 and HSP-70 were determined by enzyme-linked immunosorbent assay (ELISA). Spearman test was used to analyze the correlation between serum PGE2, HSP-70 levels and bleeding severity in PUB patients. Logistic regression was used to analyze the risk factors of PUB, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PGE2 and HSP-70 levels on the bleeding degree of PUB patients.Results:The proportion of non-steroidal anti-inflammatory drugsnon-ster (NSAID) used and Helicobacter pylori (Hp) infection, thromboplastin time (APTT) and prothrombin time (PT) in the PUB group were higher than those in the PU group: 42.00%(21/50) vs. 25.00%(18/72), 36.00%(18/50) vs. 58.33%(42/72), (28.78 ± 3.24) s vs. (26.72 ± 3.89) s, (13.14 ± 2.56) s vs. (11.26 ± 2.15) s, and the serum levels of PGE2 and HSP-70 were lower than those in the PU group: (174.25 ± 18.21) ng/L vs. (236.44 ± 24.52) ng/L, (0.78 ± 0.22) μg/L vs. (1.24 ± 0.38) μg/L, there were statistical significances ( P<0.05). The serum levels of PGE2 and HSP-70 in PUB patients decreased gradually with the severity of hemorrhage ( P<0.05). Spearman test showed that serum PGE2 and HSP-70 levels were negatively correlated with the severity of bleeding in PUB patients ( r = - 0.720, - 0.586, P<0.01). Logistic regression analysis showed that serum PGE2 and HSP-70 levels were protective factors for PUB ( P<0.05), while NSAID used, Hp infection, APTT and PT were risk factors for PUB ( P<0.05). ROC curve analysis results showed that the area under the curve of serum PGE2 and HSP-70 combined to predict the severity of bleeding in PUB patients was 0.935, which was higher than that predicted by the two indexes alone. Conclusions:The expression of serum PGE2 and HSP-70 are down regulated in PUB patients, and have correlated with the severity of bleeding. The joint detection of two indicators is more conductive to predicting the degree of bleeding in PUB patients.

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Background/Aims: The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism. Methods: The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo. Results: Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo. Conclusions Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance.

Objective:To explore the role of N 6-methyladenosine (m6A) and its regulator METTL3 in the non-coding RNA of endometrial cancer.Methods:The expression levels of m6A and METTL3 were quantified in 20 paired carcinoma and adjacent clinical tissue samples from patients at from Jul. 2016 to Dec. 2020. HEC-1-A cell lines were constructed with METTL3 overexpression and knockdown. Western blot was used to detect the phosphorylation levels of key molecules in METTL3 and Akt/mTOR. The quantitative detection of mRNA levels were used qRT-PCR. The binding level of m6A to its receptor DGCR8 was determined by RNA immunoprecipitation.Results:The results of the m6A RNA methylation quantification kit showed that m6A (1.0±0.15) vs (1.7±0.34) ( P<0.01) and METTL3 levels were elevated in endometrial cancer cells, and METTL3 (1.0±0.13) vs (2.5±0.45) ( P<0.05) levels were elevated in endometrial cancer cells. Western blot and qRT-PCR detection of miR-17-92 cell clusters overexpressing METTL3, METTL3 overexpression significantly increased m6A modification on pri-miR-17-92 ( P<0.05) . Phosphorylation levels of AKT/mTOR pathway-related proteins were upregulated. In addition, RIP test results indicated that the binding of DGCR8 to pri-miR-17-92 was significantly facilitated. Conclusion:METTL3 modification of m6A facilitates the processing of pri-miR-1792 into the miR-17-92 clusters via m6A/DGCR8-dependent mechanism, which in turn activated the AKT/mTOR pathway.

Objective:To study the efficacy and drug-related adverse reactions of long-term appli-cation of biological anti-rheumatic drugs (bDMARDs) to patients with ankylosing spondylitis (AS), and provide reference for clinical diagnosis and treatment.Methods:We retrospectively analyzed the clinical data of AS patients who were followed-up for more than 5 years in the Department of Rheumatology and Immunology of Peking University Shenzhen Hospital. The patients treated with bDMARDs alone or combined with traditional antirheumatic drugs were included as the treatment group, while those who did not receive biological or non-biological antirheumatic therapy were included as the control group. The data collected included clinical sym-ptoms, inflammatory biomarkers, imaging results, drug applications and drug-related adverse reactions, etc. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by Mann-Whitney U test. Paired test was used for statistical processing before and after treatment. Results:We collected the data of 114 eligible patients, including 64 in the treatment group and 50 in the control group. There were no significant differences in baseline data between the 2 groups, including mean follow-up time, course of disease, age, sex ratio, HLA-B27 positive rate, morning stiffness duration, night pain, peripheral arthritis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging. After 5 years, patients in the treatment group had shorter morning stiffness [(3±7) min vs (26±37) min, t=4.827, P<0.01], lower nighttime pain rates [(3/64, 4.8%) vs (29/50,58.0%), χ2=38.329, P<0.01], lower ESR level [(14±14) mm/1 h vs (20±18) mm/1 h, t=2.102, P=0.038], lower CRP level [(7±8) mg/L vs (14±19) mg/L, t=2.431, P=0.017], and lower progression rate of sacroiliac arthritis [(18/64, 28.1%) vs (35/50, 70.0%), χ2=19.786, P<0.01], than the control group. The main drug-related adverse reactions in the treatment groupincluded reversible leucopenia, elevated transaminase level, redness and swelling at the injection site. Conclusion:Biologics treatment for more than 3 consecutive years can effectively control the clinical symptoms of most AS patients, reduce inflammatory indicators and delay the imaging progression of the sacroiliac joint. Without treatment, the imaging progress of the sacroiliac joint in AS patients could be 70% after 5 years.

Objective:To investigate the effect of Astragaloside Ⅳ-mediated Endothelial progenitor cells derived exosomes (EPC-Exos) on the biological function of EPC-Exos damaged by high glicose.Methods:EPCs from human umbilical cord blood were isolated and cultured in vitro. the EPC-Exos secreted by EPCs were extracted by ultracentrifugation combined with ultrafiltration, and identified by specific markers CD9, CD63 and CD81, respectively. After the cells were cultured for 24 hours with AS-IV at 100 mg/L and PBS at the same volume, the morphological characteristics of EPC-Exos were observed by transmission electron microscope. Human endothelial cells were isolated, cultured and identified in vitro. The identified endothelial cells were pretreated with 30 mmol/L glucose for 120 h and randomly divided into experimental group and control group, at the same time set the normal group. The cells were cultured for 24 hours, the effects of EPC-Exos on proliferation, adhesion, migration and angiogenesis of endothelial cells damaged by high glucose were observed by using cell counting kit-8 (CCK-8) Cell Proliferation Assay Kit, cell scratch test, adhesion assay and in vitro angiogenesis assay by Matrigel. Results:Compared with the normal group, the proliferation, migration, adhesion and tubulogenesis of human endothelial cells in the control group were significantly lower ( t=24.35, 6.80, 10.65, 9.62, P<0.05). Compared with the control group, the proliferation, adhesion, migration and tubulogenesis of human endothelial cells in the experimental group were significantly enhanced ( t=30.68, 5.99, 5.40, 8.25, P<0.05). Conclusions:EPC-Exos mediated by AS-Ⅳ can significantly improve the biological function of human endothelial cells damaged by high glucose and has the potential to modulate endothelial neovascularization in diabetic rats.

Objective:To understand the function of diaphragm and analyze the clinical factors affecting the function of diaphragm by measuring twitch tracheal pressure (TwPtr) in patients with mechanical ventilation and in the weaning phase.Methods:Patients with more than 48 hours of invasive mechanical ventilation admitted to the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2015 to March 2017 were enrolled. After the patient entered the weaning stage, TwPtr of patients was monitored by two-way non repetitive automatic respiratory trigger device, the effects of duration of mechanical ventilation, severe pulmonary infection, sedative application and chronic obstructive pulmonary disease (COPD) on weaning were analyzed.Results:A total of 62 patients were included, of which 45 were male and 17 were female. The average age was (66.8±11.7) years old. Twenty-three cases had severe pneumonia. The absolute value of TwPtr in severe pneumonia group was lower than that in non-severe pneumonia group [cmH 2O (1 cmH 2O = 0.098 kPa): 10.40±5.81 vs. 14.35±5.22, P = 0.021]. However, there was no significant difference in the duration of mechanical ventilation between the severe pneumonia group and non-severe pneumonia group [days: 26 (17, 43) vs. 15 (11, 36), P = 0.091]. In 62 patients with mechanical ventilation, there was a negative correlation between TwPtr and duration of mechanical ventilation ( r = 0.414, P = 0.002), there was also a negative correlation between the duration of mechanical ventilation and TwPtr after the assessment of diaphragm function ( r = 0.277, P = 0.039). There was a linear relationship between TwPtr and sedatives ( r = 0.220, P = 0.040), but there was no correlation between TwPtr and COPD ( r = -0.178, P = 0.166). Conclusions:For patients in the weaning stage of mechanical ventilation, severe pulmonary infection is one of the factors that affect the diaphragm dysfunction. There is a certain correlation between the diaphragm dysfunction and the use of sedatives.

Objective:To observe the long-term effects of conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of ankylosing spondylitis (AS) and drug-related adverse reactions, and provide reference to clinical treatment and assessment.Methods:Retrospective analysis was performed for AS patients with more than 10 years follow-up records in the Department of Rheumatology and Immunology, Peking University Shenzhen Hospital. The AS patients enrolled were treated with cDMARDs, non-steroid anti-inflammatory Drugs (NSAIDs), and glucocorticoidsonl only. The treatment group was treated continuously for at least 3 years, and the control group was untreated or treated for less than 3 months. Clinical symptoms, inflammatory indicators, imaging results and drug-related adverse reactions of all patients were collected for statistical analysis. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by mann-whitney U test. Paired test was used for statistical processing before and after treatment. Results:A total of 166 eligible patients were included, including 111 in the treatment group and 55 in the control group. There were no statistical significant differences between the treatment group and the control group at baseline including the mean follow-up time, symptomatic disease course, age, sex ratio, human lymphocyte antigen (HLA)-B27 positive rate, duration of morning stiffness, pain at night, peripheral arthritis, ESR, CRP and imaging data. After 10 years, the treat-ment group had shorter morning stiffness[(8±18) vs (22±34), U=2 228, P=0.008], less nocturnal pain [(2/1.9%) vs (19/36.5%), χ2=37.037, P<0.01], lower ESR level [(14±13) vs (20±19), t=2.249, P=0.026], lower CRP level [(6±6) vs (10±11), t=2.154, P=0.033], lower incidence of peripheral arthritis [(23/20.7%) vs(25/45.5%), χ2=10.946, P=0.001] and lower sacroiliac arthritis progression rate [(28/25.2% ) vs (46/83.6%), χ2=50.922, P<0.01], and lower spinal progression rate [(8/7.2%) vs (51/92.7%), χ2=117.407, P<0.01] compared with the control group. The differences between the two groups was statistically significant. The main medications and drug proportions in the treatment group were as follows: sulfasalazine (100%), methotrexate (86.5%), NSAIDs (98.2%), glucocorticoid (78.4%) and thalidomide (62.2%). The main drug-related adverse reactions that occurred during the treatment included dizziness, abnormal menstruation, and reversible liver dysfunction. Conclusion:The combination of cDMARDs can effectively control the clinical symptoms of most AS patients, reduce inflammation indicators, delay the progression of sacroiliac joint and spinal damage, and have no serious drug-related adverse reactions. Almost all of the untreated AS patients have radiographic progression of the sacroiliac joint and spine.