A miRNA-disease association prediction model based on tree-path global feature extraction and fully connected artificial neural network with multi-head self-attention mechanism.

BACKGROUND: MicroRNAs (miRNAs) emerge in various organisms, ranging from viruses to humans, and play crucial regulatory roles within cells, participating in a variety of biological processes. In numerous prediction methods for miRNA-disease associations, the issue of over-dependence on both similarity measurement data and the association matrix still hasn't been improved. In this paper, a miRNA-Disease association prediction model (called TP-MDA) based on tree path global feature extraction and fully connected artificial neural network (FANN) with multi-head self-attention mechanism is proposed. The TP-MDA model utilizes an association tree structure to represent the data relationships, multi-head self-attention mechanism for extracting feature vectors, and fully connected artificial neural network with 5-fold cross-validation for model training. RESULTS: The experimental results indicate that the TP-MDA model outperforms the other comparative models, AUC is 0.9714. In the case studies of miRNAs associated with colorectal cancer and lung cancer, among the top 15 miRNAs predicted by the model, 12 in colorectal cancer and 15 in lung cancer were validated respectively, the accuracy is as high as 0.9227. CONCLUSIONS: The model proposed in this paper can accurately predict the miRNA-disease association, and can serve as a valuable reference for data mining and association prediction in the fields of life sciences, biology, and disease genetics, among others.

Value of alkaline phosphatase level after ursodeoxycholic acid treatment for one month and baseline red blood cell distribution width in predicting the treatment response of primary biliary cholangitis / 临床肝胆病杂志

ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ2=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ2=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study.

Objective: To explore the difference in gut microbiota between different traditional Chinese Medicine (TCM) syndromes in patients with colorectal cancer (CRC) and its internal relationship. Methods: From June 2020 to August 2021, 109 colorectal cancer patients with a clear pathological diagnosis who had not yet undergone surgery or chemotherapy were classified according to the TCM syndrome classification, and the feces samples of 109 patients with preoperative colorectal cancer were collected. 16s rRNA gene sequencing was used to determine gut microbiota diversity and abundance in CRC patients with different TCM syndrome, and LEfSe analysis was made to screen different TCM syndrome for differential representative microbiota. Results: 109 patients were divided into 5 syndromes by TCM syndrome classification, which were Liver and Kidney Yin Deficiency Syndrome (LKYDS, n = 19), Spleen Deficient Qi Stagnation Syndrome (SDQSS, n = 30), Stasis and Poison Obstruction Syndrome (SPOS, n = 17), Damp-Heat Syndrome (DHS, n = 30), Qi and Blood Deficiency Syndrome (QBDS, n = 13). Alpha diversity index showed significant differences among the five groups of TCM syndromes, with Shannon index being highest in the SDQSS group and lowest in the LKYDS (p = 0.003). ACE index being highest in the SDQSS group and lowest in the SPOS (p = 0.010). PD whole tree index being highest in the SDQSS group and lowest in the SPOS (p = 0.017). Similarly, beta diversity showed significant differences among the five groups of TCM syndromes, with principal coordinate analysis (PCo1 = 31.86 %, PCo2 = 5.62 %) showing separation and coincidence between the groups, and Adonis group differences showing coincidence between the QBDS-LKYDS (p = 0.702), QBDS-DHS (p = 0.133), and SDQSS-DHS (p = 0.260) groups. LEfSe analysis revealed that the representative microbiota of DHS patients was Dialister sp Marseille P5638 (LDA = 3.05, p＜0.001), the representative microbiota of SPOS patients was Oscillospirales (LDA = 4.78, p = 0.029), the representative microbiota of SDQSS patients was Selenomonadaceae (LDA = 3.94, p = 0.003), the representative microbiota of LKYDS patients was Dialister (LDA = 4.19, p = 0.001), and the representative microbiota of QBDS patients was Akkermansia muciniphila (LDA = 4.23, p = 0.006). Conclusions: There are significant differences in gut microbiota between different TCM syndromes in CRC patients. The five microbiota, Dialister sp Marseille P5638, Oscillospirales, Selenomonadaceae, Dialister, and Akkermansia muciniphila, may be differential markers of TCM syndrome in CRC and are expected to be one of the bases for accurate TCM syndrome differentiation of CRC.

IL-33 Suppresses the Progression of Atherosclerosis via the ERK1/2-IRF1-VCAM-1 Pathway.

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

Conduction system pacing for ventricular pacing requirement is feasible and effective on patients with hypertrophic cardiomyopathy and cardiac dysfunction.

Objective: We aimed to evaluate the feasibility and safety of his-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with hypertrophic cardiomyopathy (HCM) and heart failure (HF). Methods: Patients with HF and interventricular septal thickness (IVST) ≥ 13 mm resulted from HCM, who accepted conduction system pacing (CSP) with a percentage of ventricular pacing > 40% from May 2018 to April 2022 were consecutively enrolled in our center. LBBP was preferred and HBP was the alternative therapy unless IVST ≥ 16 mm or LBBP failed, whereas LBBP would be the alternative therapy if HBP failed in patients with IVST ≥ 16 mm. All patients were followed up for at least one year. Data including clinical, echocardiographic parameters and electrocardiogram measurements, were collected and evaluated in patients with and without left ventricular ejection fraction (LVEF) < 50%. Results: A total of 27 patients (65.93 ± 9.09 years old) were enrolled and only 3 patients failed in CSP (11.11%) via LBBP (6/13) and HBP (18/21) procedures. LVEF (P = 0.521), left ventricular end-diastolic diameter (LVEDD) (P = 0.816), and QRS duration (P = 0.928) did not worsen after CSP, and left atrial diameter (LAD) (49.58 ± 8.99 mm vs.47.04 ± 9.82 mm, P = 0.045) tended to improve slightly after 19.19 ± 7.71 months follow-up. Of note, LVEF (39.22%±7.51% vs. 45.22%±9.59%, P = 0.015), LVEDD (52.11 ± 10.10 mm vs. 48.33 ± 9.07 mm, P = 0.037), LAD (50.33 ± 8.93 mm vs. 46.11 ± 5.97 mm, P = 0.013) and New York Heart Association (NYHA) grade (2.67 ± 0.5 vs. 1.38 ± 1.02, P = 0.029) improved in 9 patients with LVEF < 50%, whereas LVEF (P = 0.372), LVEDD (P = 0.665), LAD (P = 0.093) and NYHA grade (P = 0.452) did not deteriorate in patients with preserved ejection fraction. Conclusion: CSP was safe and feasible in patients with HCM and cardiac dysfunction, and did not worsen cardiac performance especially in patients with LVEF < 50%. HBP might be an effective alternative to LBBP in patients with significantly thickened interventricular septum.

The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is the sixth most common cancer in women. P53 gene expression in patients with endometrial cancer can predict the efficacy and prognosis of patients with neoadjuvant therapy. PURPOSE: To explore the value of multimodal magnetic resonance imaging (MRI) in differentiating p53 abnormal (p53abn) from p53 wild-type (p53wt) EC. MATERIAL AND METHODS: Data from 47 EC patients, including 14 p53abn cases and 33 p53wt cases, were retrospectively analyzed. The preoperative MRI sequences included amide proton transfer weighted (APTw) imaging, T2 mapping, mDIXON-Quant imaging and diffusion-weighted imaging (DWI). After post-processing, APT, T2, transverse relaxation rate (R2*), fat fraction (FF) and apparent diffusion coefficient (ADC) maps were obtained. The APT, T2, R2*, FF and ADC values for lesions of the two groups of cases were measured by two observers who were blind to the pathological data. RESULTS: The APT value and R2* value in the p53abn group were higher than those in the p53wt group, while the ADC value was lower (all P < 0.05). There was no statistically significant difference in T2 value and FF value between the two groups (all P > 0.05). The area under curve of APT, R2*, ADC and combined APT + R2*+ADC values for identification of p53abn and p53wt EC were 0.739, 0.689, 0.718 and 0.820, respectively (all P > 0.05). CONCLUSION: APTw, mDIXON-Quant and DWI techniques can be usedfor quantitative identification of p53abn and p53wt EC. The multimodal MRI provides a new way for preoperative quantitative evaluation of EC molecular typing, which has certain clinical application value.

Spatial distribution characteristics of sediment connectivity and soil erosion in small watershed in brown soil hilly region of low mountains in western Liaoning Province, China.

Understanding the spatial distribution characteristics of soil erosion and sediment connectivity is important for formulating integrated watershed management measures. Based on the InVEST sediment delivery ratio model, we used the connectivity index and soil loss model to measure the spatial distribution characteristics of sediment connectivity and soil erosion in Erdaoling watershed of brown soil hilly region of low mountains in western Liaoning. By exploring slope, aspect and land use characteristics under different sediment connectivity levels and soil erosion levels, we analyzed the relationships among topography, land use, sediment connectivity, and soil erosion. The results showed that the average sediment connectivity in the watershed was -3.79, and that the average soil erosion was 614 t·km2·a-1. High connectivity was mainly found in sloping farmland, while low connectivity was mainly found in forest and grassland. The soil erosion intensity of 93.3% of the watershed area was below moderate, with only 1.1% of the area being above extremely strong. The higher the sediment connectivity level, the higher the proportion of the area <5° slope, while the area proportion of the rest slope was relatively stable. The proportion of cultivated land area increased, while the proportion of forest and grassland land area decreased. The area proportion on negative slope decreased, while that on positive slope increased. With increasing soil erosion intensity, the area proportion of slope <8° increased and the area proportion of the rest slope was relatively stable. The proportion of forest and grassland area decreased, while the proportion of other land use area increased. The proportion of slope area on positive slope increased, while that on negative slope decreased. Land use was a key factor influencing the spatial response relationship between soil erosion and sediment connectivity in this watershed.

Study on the preparation and luminescence properties of SrGe4 O9 :Mn4+ red phosphors for plant illumination.

In this study, SrGe4 O9 :Mn4+ red phosphors for plant illumination were prepared using a high-temperature solid-phase method. The samples were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), fluorescence spectroscopy, and other techniques. The phase structure, apparent morphology, and luminescence properties of the SrGe4 O9 :Mn4+ red phosphors were investigated. The results indicated that the dopant Mn4+ was incorporated into the matrix structure by substituting some Ge4+ ions without any changes in the crystal structure of the SrGe4 O9 matrix. The samples comprised micron-scale particles and exhibited high purity and uniform distribution of elements. The SrGe4 O9 :Mn4+ phosphors exhibited relatively strong red light emission at 660 nm under the excitation of a 430-nm blue light, and the luminescence intensity was the highest when the Mn4+ doping amount was 1%. Proper doping of Ti4+ or Sn4+ could effectively improve the luminescence intensity of the SrGe4 O9 :Mn4+ phosphors. The light-emitting diode (LED) device packaging showed that the SrGe4 O9 :Mn4+ red phosphors could be used for plant growth illumination.

Correlation and predictive effect of subjective and objective balance function measurements in stroke patients with hemiplegia / 中国康复理论与实践

ObjectiveTo explore the correlation of index of standing balance tester to score of Berg Balance Scale (BBS) and Fugl-Meyer Assment-Lower Extremites (FMA-LE) in stroke patients with hemiplegia, and analyze the predictive effect to BBS. MethodsFrom March to October, 2022, 66 stroke hemiplegic patients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were selected. The elliptical area and length of motion were measured with a balance tester when they were standing with eyes open or closed, respectively. They were also evaluated with BBS and FMA-LE. The correlation between the test results and the scores of BBS and FMA-LE was analyzed with Pearson's correlation analysis, and the predictive effect of the test results to the score of BBS was also analyzed with receiver operating characteristic (ROC) curve. ResultsHypertension, diabetes, coronary heart disease, smoking and alcohol drinking were not significant for the scores of BBS and FMA-LE (|t| < 1.124, P > 0.05). In the balance test, the eye opening movement ellipse area, eye opening movement length, eye closing movement ellipse area and eye closing movement length were negatively correlated with the scores of BBS and FMA-LE (|r| > 0.250, P < 0.05). The area under the ROC curve of eye opening movement ellipse area to the score of BBS was 0.685 (P = 0.019), and the area under the ROC curve of the eye opening movement length to the score of BBS was 0.764 (P < 0.001). ConclusionThe open eye movement ellipse area, open eye movement length, closed eye movement ellipse area and closed eye movement length are significantly negatively correlated with the scores of BBS and FMA-UE. The indexes of the balance test with eyes open may predict the score of BBS.

Acoustic analysis of an articulation assessment and training system / 中华物理医学与康复杂志

Objective:To compare the differences in important parameters between the articulation assessment and training system of intelligently extracted speech with those from the Praat acoustic software and those manually extracted.Methods:The speech of thirty-two normal subjects was captured using the intelligent articulation assessment and training system and using Praat acoustic software. The former analyzed the mean fundamental frequencies (mF0s), the first formant peaks (F1s) and the second formant peak (F2s) of the sustained vowels /a/, /i/ and /u/. The speech parameters collected by the traditional Praat software were extracted and analyzed by professionals. The two tools′ consistency in terms of these important acoustic parameters was analyzed.Results:The results with all 32 subjects when retested returned ICC values above 0.9 with all three vowels with the exception of mF0 for /u/ (ICC=0.75), indicating excellent retest reliability for the articulation assessment and training system. The ICC values also indicated excellent consistency between the two kinds of software in analyzing mF0, F1 and F2 of the three vowels. The mF0, F1, F2, FCR, VAI, tongue spacing, VSA, and mandibular spacing of all three vowels were mostly distributed within the 95% confidence interval of the data points in Bland-Altman plots, indicating the high accuracy of both acoustic analysis systems in speech measurement. The mean fundamental frequency values of the male long vowels /a/, /i/ and /u/ were all significantly lower than for the female long versions.Conclusions:The retest reliability of the articulation assessment and training system was good, and the results of the articulation check in the natural state were in good consistency compared to the Praat check and were interchangeable in the articulation check.

Research progress on the bone-marrow sparing intensity-modulated radiotherapy for cervical cancer / 中华放射肿瘤学杂志

The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.

Consistency study of FRACTURE sequence and CT in evaluating bone changes of knee and ankle / 中华放射学杂志

Objective:To explore the consistency of MRI fast field echo resembling a CT using restricted echo-spacing (FRACTURE) and CT in the evaluation of knee and ankle bone changes.Methods:From November 2020 to November 2021, seventeen patients who underwent CT and MRI FRACTURE examinations of knee joint or ankle joint in the First Affiliated Hospital of Dalian Medical University were retrospectively collected, including 14 patients with knee joint examinations and 3 patients with ankle joint examinations. According to the number of joint components, 80 components were included, including 14 for femur and patella, 17 for tibia and fibula, and 3 for talus, scaphoid, medial cuneiform, medial cuneiform, lateral cuneiform and calcaneus, respectively. The fracture, hyperosteogeny, and bone destruction of the joint bones were evaluated by two observers using CT and FRACTURE images, respectively. Kappa test was used to analyze the consistency of CT and FRACTURE images between observers in the evaluation of joint bone lesions.Results:The Kappa values (95%CI) of the consistency evaluation of fracture, hyperosteogeny, and bone destruction by CT and FRACTURE images were 0.925 (0.823-1.027), 0.905 (0.799-1.011) and 0.895(0.752-1.038) respectively for observer 1, and were 0.963 (0.892-1.034), 0.933 (0.843-1.023) and 0.886 (0.731-1.041) respectively for observer 2. The Kappa values (95%CI) of the consistency evaluation of fracture, hyperosteogeny, and bone destruction by observers 1 and 2 via CT images were 1.000 (1.000-1.000), 0.937(0.851-1.023) and 0.945 (0.839-1.051) respectively, and that by FRACTURE images were 0.962 (0.888-1.036), 0.966 (0.899-1.033) and 0.836 (0.656-1.016) respectively.Conclusion:For the evaluation of fracture, hyperosteogeny, and bone destruction of knee joint and ankle joint, MRI FRACTURE sequence is highly consistent with CT.

Clinical characteristics of asymptomatic infection of brucellosis / 中华地方病学杂志

Objective:To analyze the clinical characteristics of asymptomatic infection of brucellosis, in order to provide reference for prevention and treatment of brucellosis.Methods:Retrospective analysis was used to collect the clinical data of patients with brucellosis asymptomatic infection and confirmed cases admitted to the 940th Hospital of Joint Logistics Support Force of Chinese PLA from 2017 to 2021, and the demography characteristics, clinical manifestations and laboratory test results were analyzed.Results:The results showed that a total of 18 cases of asymptomatic infection and 85 confirmed cases of brucellosis were included, and there was no statistically significant difference in age, gender, occupation and ethnicity distribution between the two groups ( F = 7.09, χ 2 = 0.74, 4.02, 0.55, P = 0.295, 0.785, 0.327, 1.000). The 18 cases of asymptomatic infection of brucellosis were found through screening in key populations, and no clinical symptoms or abnormal imaging signs were observed. The clinical symptoms of 85 confirmed cases were mainly muscle and joint pain, fever, sweating, fatigue, and low back pain; and the imaging manifestations were mainly arthritis, splenomegaly, and spondylitis. The median percentage of eosinophils (0.70%, 1.40%), percentage of basophils (3.05%, 0.40%), C-reactive protein (1.62, 4.62 mg/L), erythrocyte sedimentation rate (1.00, 11.00 mm/h), and antibody titer of serum agglutination test (1 ∶ 100, 1 ∶ 200) showed statistically significant differences between asymptomatic infection and confirmed cases of brucellosis ( Z = - 2.97, - 5.11, - 3.49, - 3.21, - 3.50, P = 0.003, 0.001, 0.001, 0.001, 0.007). Conclusions:There is a difference in the composition of granulocytes between asymptomatic infection and confirmed cases of brucellosis, and the level of inflammatory response indicators is lower than that of confirmed cases. Regular seroepidemiological surveys among key populations can help screen for asymptomatic infection of brucellosis.

Effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer / 中华消化外科杂志

Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.

The protective effect of trigonelline on H / 中国药理学通报

Aim To study the protective effect of trigonelline on H

Effects of stilbenes on glucose and lipid metabolism in insulin resistant HepG2 cells / 中国药理学通报

Aim To explore the effect of four stilbenes including rhaponticin, desoxyrhaponticin, rhapontigenin and resveratrol on glucose and lipid metabolism in insulin-resistant HepG2 cells induced by high glucose and high fat. Methods The model of insulin resistance was established by incubating HepG2 cells with a complex of glucose and oleic acid. MTT assay was used to detect cell viability. The intracellular triglyceride (TG) and glucose levels were measured by the kit method. The lipid production was observed by oil red O staining, and the cell morphology and uptake of 2-NBDG were observed by confocal microscope. The PPAR signaling pathway and PI3K/Akt insulin signaling pathway related proteins were determined by Western blot to evaluate the effect of stilbenes on glycolipid metabolism in IR-HepG2 cells. Results The complex containing 50 mmol • L

Auranofin reverses acquired resistance to osimertinib in non-small cell lung cancer / 中国药理学通报

Aim To investigate the role of auranofin in reversing acquired resistance to osimertinib in non-small cell lung cancer. Methods Osimertinib-sensi-tive NSCLC cell lines HI975 and PC9 were used to establish osimertinib-resistant NSCLC cell lines HI975/OR and PC9/OR. An FDA approved library of 1470 FDA drugs was used to high-throughput screen the reversal agents of acquired resistant of osimertinib by CCK-8. Compusyn was used to calculate the combination index of osimertinib and auranofin to determine the optimal dose of drug combination. CCK-8, EdU, flow cytometry and Transwell experiments were used to detect osimertinib, auranofin and the combination drug effect on proliferation, apoptosis, migration and invasion of osimertinib acquired NSCLC cell lines. RNA-sequencing was applied to screen differentially expressed mRNAs in osimertinib treatment alone and osimertinib combined with auranofin treatment group. qRT-PCR and western blot were employed to validate the selected gene expression and protein expression. Results Compared with osimertinib sensitive cell lines H1975 and PC9, H1975/OR and PC9/OR showed significantly higher cell viability and lower apoptosis rate after osimertinib treatment. The resistance index was 70. 31 and 136. 99, respectively. In FDA approved 1470 drug library, only auranofin could enhance the sensitivity of osimertinib in H1975/OR and PC9/OR. When 1 μmol • L

Lanthanum hydroxide inhibits CKD-induced vascular calcification by blocking HIF-1α signaling pathway / 中国药理学通报

Aim To investigate the therapeutic effect of lanthanum hydroxide on renal injury and vascular calcification in rats caused by chronic kidney disease (CKD) and the underlying mechanism. Methods A CKD model was constructed by adenine, and the rats were randomly divided into model group, lanthanum hydroxide low, medium and high dose groups, lanthanum carbonate group and calcium carbonate group. After eight weeks, serum phosphorus ( Pi ), calcium (Ca), serum creatinine ( Scr), blood urea nitrogen ( BUN ), parathyroid hormone ( PTH ), fibroblast growth factor 23 ( FGF23 ) and tartrate-resistant acid phosphatase 5b ( TARP-5b) levels were measured. Histopathological staining was used to assess the degree of calcification of blood vessels, and the expressions of smooth muscle protein 22α ( SM22α), Runt-related transcription factor 2 ( RUNX2 ), hypoxia inducible factor 1 ( HIF-1) pathway mRNA and protein expression in blood vessels were detected. Results Lanthanum hydroxide can significantly reduce the levels of Pi, Scr, BUN, PTH, FGF23 and TARP-5b in the serum of CKD rats, significantly reduce the calcium deposition of the thoracic aorta of CKD rats, the expression of BMP-2, VEGF in the cytoplasm, the expression of RUNX2, HIF-1α in the nucleus, and increase the mRNA and protein expression of SM22. Conclusion Lanthanum hydroxide can markedly improve hyperphosphatemia in CKD rats, and can improve vascular calcification in CKD rats by blocking HIF-1α signaling pathway.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/μl vs 852 cells/μl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.