Objective To observe the effects of pegylated losenatide injection combined with metformin tablets on serum metabolism,lipid levels and intestinal flora in obese type 2 diabetes mellitus(T2DM)patients after axial gastrectomy.Methods Obese T2DM patients who underwent axial gastrectomy were divided into treatment group and control group by cohort methods.The control group was treated with metformin hydrochloride tablet 0.5 g orally,tid.The treatment group was treated by subcutaneous injection of pegylated losenatide injection 0.2 mg once a week on the basis of control group.Both groups were treated continuously for 3 months.Body mass index(BMI),serum metabolic indexes,blood lipid levels,blood glucose levels,intestinal flora and adverse drug reactions were compared between the two groups.Results In this study,a total of 70 subjects were included in the treatment group,and 50 subjects were included in the control group.After three months of treatment,the BMI indices of the treatment and control groups were(26.35±2.36)and(29.34±3.59)kg·m-2,respectively;the glutathione peroxidase levels were(192.42±13.18)and(134.27±12.86)U;interleukin-6 levels were(6.14±1.78)and(7.65±2.09)μg·L-1;fasting blood glucose levels were(5.36±0.41)and(7.43±0.78)mmol·L-1;total cholesterol levels were(2.55±0.67)and(3.47±0.79)mmol·L-1 for the treatment and control groups,respectively.The levels of Bifidobacteria,Bacteroides,Lactobacilli,Enterobacteria,and Enterococci in the treatment group were(8.79±1.36),(9.62±1.37),(6.74±2.15),(7.98±0.61),and(7.23±1.29)logN·g-1,respectively;in the control group,these levels were(7.98±1.79),(8.13±1.45),(5.71±2.41),(9.21±0.88),and(8.15±1.54)logN·g-1.The differences in the above indicators between the treatment and control groups were statistically significant(all P＜0.05).The main adverse drug reactions in the treatment group included nausea,headache,dizziness,elevated blood pressure,and indigestion.In the control group,the main adverse drug reactions were nausea,headache,and indigestion.The total incidence of adverse drug reactions in the treatment and control groups was 8.57％and 6.00％,respectively,with no statistically significant difference(P＞0.05).Conclusion Pegylated losenatide injection combined with metformin tablets has a significant effect on axial gastrectomy in obese type 2 diabetes patients.

Ferroptosis is an iron-dependent form of programmed cell death triggered by the excessive accumulation of lipid peroxides on the cell membrane.Recent studies have found that ferroptosis can be induced by exposure of the testis tissue and germ cells to some high-risk factors,accompanied by various characteristic reproductive system injuries,including changes in cell morphology,ferroptosis-related physico-chemical indicators and gene expressions.This review focuses on the association of ferroptosis with male reproductive system diseases from three key aspects:iron metabolism abnormalities,Cystine/GSH/GPX4 axis imbalance,and lipid peroxidation.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.
Humans ; Bacterial Toxins/genetics* ; Enterotoxins/genetics* ; Clostridioides difficile/genetics* ; Multilocus Sequence Typing ; Coinfection ; Bacterial Proteins/genetics* ; China/epidemiology* ; Clostridium Infections/epidemiology* ; Diarrhea/microbiology*

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.
Hot Temperature ; Humans ; Moxibustion ; Patient Preference ; Random Allocation ; Reproducibility of Results

PURPOSE: Auditory nerve injury is one of the most common nerve injury complications of skull base fractures. However, there is currently a lack of auxiliary examination methods for its direct diagnosis. The purpose of this study was to find a more efficient and accurate means of diagnosis for auditory nerve injury. METHODS: Through retrospectively analyzing the results of brainstem auditory evoked potential (BAEP) and high-resolution CT (HRCT) in 37 patients with hearing impairment following trauma from January 1, 2018 to July 31, 2020, the role of the two inspection methods in the diagnosis of auditory nerve injury was studied. Inclusion criteria were patient had a clear history of trauma and unilateral hearing impairment after trauma; while exclusion criteria were: (1) severe patient with a Glasgow coma scale score ≤5 because these patients were classified as severe head injury and admitted to the intensive care unit, (2) patient in the subacute stage admitted 72 h after trauma, and (3) patient with prior hearing impairment before trauma. According to Goodman's classification of hearing impairment, the patients were divided into low/medium/severe injury groups. In addition, patients were divided into HRCT-positive and negative groups for further investigation with their BAEP results. The positive rates of BEAP for each group were observed, and the results were analyzed by Chi-square test (p < 0.05, regarded as statistical difference). RESULTS: A total of 37 patients were included, including 21 males and 16 females. All of them were hospitalized patients with GCS score of 6-15 at the time of admission. The BAEP positive rate in the medium and severe injury group was 100%, which was significantly higher than that in the low injury group (27.27%) (p < 0.01). The rate of BEAP positivity was significantly higher in the HRCT-positive group (20/30, 66.7%) than in the HRCT-negative group (1/7, 14.3%) (p < 0.05). Twenty patients (54.05%) were both positive for BEAP and HRCT test, and considered to have auditory nerve damage. Six patients (16.22%) were both negative for BEAP and HRCT test, and 10 patients (27.03%) were BAEP-negative but HRCT-positive: all the 16 patients were considered as non-neurological injury. The rest 1 case (2.70%) was BAEP-positive but HRCT-negative, which we speculate may have auditory nerve concussion. CONCLUSION By way of BAEP combining with skull base HRCT, we may improve the accuracy of the diagnosis of auditory nerve injury. Such a diagnostic strategy may be beneficial to guiding treatment plans and evaluating prognosis.
Cochlear Nerve ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Female ; Hearing Loss ; Humans ; Male ; Retrospective Studies ; Skull Base/diagnostic imaging* ; Tomography, X-Ray Computed

Based on the community research experience of heat-sensitive moxibustion, this study explained technical recommendations for pragmatic randomized controlled trials (pRCTs) of heat-sensitive moxibustion in community from 7 aspects: selection of community research sites, ethical approval and registration, patient recruitment, training of standard operating procedures, ensuring patient compliance, quality control of follow-up visits and patient safety, which aimed to reduce the difficulty of research execution and improve the quality of pRCTs implementation and follow-up visits of heat-sensitive moxibustion.
Follow-Up Studies ; Hot Temperature ; Humans ; Moxibustion/methods* ; Randomized Controlled Trials as Topic

ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg^-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg^-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E₂ （PGE₂） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE₂ contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg