Objective To investigate the mechanism of miR-135a/MYC-mediated resistance to venaclar treatment in myelodysplastic syndromes(MDS)with acute myeloid leukaemia(AML).Methods Eighty-six cases of patients were selected,including 23 healthy donors(control group),47 MDS patients with vinecella resistance(MDS group),and 16 AML patients with vinecella resistance transformed from myelodysplastic syndrome(AML group).The expression levels of miR-135a and MYC in the tissues of the three groups were detected.THP1 cells were divided into miR-NC group(transfected with nonsense sequence)and miR-135a minics group(transfected with miR-135a minics),and the cells were treated with venaclar concentration of 0,0.01,1,and 100 μmol·L-1 for 24 hours,and then detected the cell viability and apoptosis rate in each group.Results The expression of MYC mRNA were 1.00±0.14,0.21±0.04,and 0.25±0.08 in patients of the NC,MDS,and AML groups,respectively;the protein expression of MYC were 1.00±0.15,1.31±0.12 and 1.49±0.16,respectively(P＜0.05).At the cellular level,miR-135a expression were 1.00±0.11,1.31±0.15 and 1.93±0.23 in the BMSCs,MUTZ-1 and THP1 groups;MYC protein expression were 1.00±0.15,1.57±0.22 and 1.97±0.31,the differences were significant(P＜0.05).The methods showed the cell viability of miR-NC group were(100.00±13.26)％,(92.33±10.28)％,(85.41±11.37)％and(28.24±6.02)％at 0,0.01,1,100 μmol·L-1venaclar drug concentration,respectively;cell viability of miR-135a mimics group were(105.12±12.35)％,(82.11±12.07)％,(46.13±8.06)％and(18.20±5.03)％,respectively,there was statistical difference between the two groups only in the 1 μmol·L-1 venaclar drug concentration(P＜0.05).The methods showed that the apoptosis rates in miR-NC group at 0,0.01,1,100 μmol·L-1 venaclar drug concentration were(100.00±11.45)％,(92.48±12.04)％,(108.72±9.63)％and(207.15±21.49)％,the apoptosis rates in miR-135a mimics group were(106.34±16.21)％,(117.26±10.13)％,(269.41±23.59)％and(184.33±19.28)％,respectively;there was statistical difference between the two groups only in 1 μmol·L-1 venaclar drug concentration(P＜0.05).Conclusion The results of this study reveal that miR-135a/MYC mediates the mechanism of resistance to venaclar in the treatment of MDS and AML.

AIM:To explore the fundus vascular characteristics of healthy individuals based on deep learning techniques, with a view to discovering the range of normal values of the fundus arteries and veins, as well as the relationship between physiological factors, such as gender, age, body mass index(BMI), blood pressure, and fundus vasculature characteristics.METHODS:Fundus images of healthy people were taken from a professional fundus camera, and the subject's blood pressure and laboratory test was collected. Additionally, the fundus arteries and veins were segmented by the improved U-Net model, and the color, morphology and Haralick texture features of the vessels were extracted from computer vision technology.RESULTS:A total of 4 487 cases fundus images were taken and 326 cases with healthy and clear fundus images were screened, including 200 males and 126 females. There were differences in the morphology, color, and textural characteristics of the left and right eyes, as well as of the fundus arterioles and veins, with a mean vessel width(width)of 1.146 in the arteries and 1.430 in the veins, and an arteriovenous ratio about 4:5. Fundus artery and vein characteristics in healthy individuals of different ages(21-30, 31-40, 41-50): compared with the healthy population aged 21-30 and 31-40 years, arterial and venous inverse difference moment(idm), f12 and venous angular second moment(asm)values increased, and arterial and venous contrast(con), entropy(ent), difference entropy(den), and venous sum entropy(sen)values decreased in 41-50 years. Compared with the 21-30 years age group, arterial f12 values increased and venous con values decreased in 31-40 years(all P<0.05). Fundus vascular characteristics of healthy individuals of different sexes: compared with male, fundus arterial and venous sum average(sav), sum variance(sva)values, arterial curved values, and venous b mean, bsd, variance(var), sen, ent values increased in female, while venous area value of female decreased(all P<0.05). There were no statistically significant differences in fundus arteriosus and venous features in healthy subjects with different levels of BMI(all P>0.05). Fundus characteristics of healthy people with different degrees of blood pressure: there were statistically significant differences in fundus arteriosus area, width, and venous con, idm, dva, and den values between the normal blood pressure and high blood pressure groups(all P<0.05).CONCLUSION: The characteristics of the left and right eyes as well as the fundus arteries and veins differ in healthy individuals and correlate with physiological factors such as gender, age and blood pressure, which have the value of a potential microcirculation marker.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective To observe the clinical value of recombinant human erythropoietin injection in the treatment of anemia after chemotherapy in leukemia patients,and to explore the difference of efficacy of different doses.Methods Patients with anemia complicated by leukemia chemotherapy were selected as the study objects and randomly divided into control group,low-dose group and high-dose group.Patients in the control group received conventional treatment(oral ferrous succinate combined with dietary conditioning),and patients in the low-dose group were given 75 U·kg-1 recombinant human erythrophorin treatment on the basis of the control group,subcutaneous injection 3 times a week.High-dose group was treated with 150 U·kg-1 recombinant human erythropoietin on the basis of control group,subcutaneous injection 3 times a week.All three groups were treated for 4 weeks.The clinical efficacy,the anemia-related indexes,the expression of mitogen-activated protein kinase path-related proteins in bone marrow stromal cells,Karnofsky performance status(KPS)score and safety of the three groups were compared.Result Control group,low-dose group and high-dose group were enrolled in 32,33 and 33 cases,respectively,without shedding patients.After treatment,the total effective rate of control group,low-dose group and high-dose group were 62.50％(20 cases/32 cases),78.79％(26 cases/33 cases)and 87.88％(29 cases/33 cases),respectively.There was statistical significance in the total effective rate of control group and high-dose group(P＜0.05).After treatment,the hemoglobin levels of control group,low-dose group and high-dose group were(108.76±6.82),(112.43±7.31)and(116.27±7.72)g·L-1,respectively;red blood cell counts were(3.08±0.42)× 1012,(3.34±0.39)× 1012 and(3.58±0.45)× 1012·L-1,respectively;hematocrit were 0.28±0.05,0.31±0.06 and 0.35±0.07,respectively;the relative expression levels of phosphorylated extracellular regulatory protein kinase 1/2 were 1.12±0.16,1.23±0.17 and 1.35±0.22,respectively;the relative expression levels of phosphorylated stress-activated protein kinase were 0.83±0.13,0.76±0.11 and 0.69±0.09,respectively;the expression levels of p-P38 were 0.92±0.10,0.86±0.09 and 0.80±0.09,respectively;the KPS scores were(69.35±6.43),(72.84±6.62)and(76.35±6.77)points,respectively.The above indexes in the low-dose group and the high-dose group were compared with the control group,respectively,and the above indexes in the high-dose group were compared with the low-dose group,and the differences were statistically significant(all P＜0.05).The adverse drug reactions in the three groups were mainly skin allergy and gastrointestinal reactions.The total incidences of adverse drug reactions in the control group,low-dose group and high-dose group was 12.50％,18.18％and 18.18％,respectively,with no statistical significance(all P＞0.05).Conclusion Recombinant human erythropoietin can significantly correct chemotherapy related anemia in leukemia,and improve health status,and the curative effect of 150 U·kg-1 was better than 75 U·kg-1.

Recently,inductively coupled plasma mass spectrometry(ICP-MS)has shown great potential in the quantitative analysis of biomolecules due to its high sensitivity,high accuracy,anti-interference ability and multi-element detection capability.Elemental tags enable specific labeling of target biomolecules with element-reporter groups,playing a critical role in the performance of bioanalysis using ICP-MS.Antibodies are highly specific to antigens on cell surfaces and are one of the most commonly used targeted delivery vehicles.Traditional random chemical coupling methods are difficult to control the coupling sites and loading numbers of element reporters,which lead to heterogeneity of antibody conjugates,affecting the specific recognition and binding ability of antibodies and antigens,and thus reducing the targeting ability and quantitative accuracy.To solve these issues,site-specific coupling of antibodies with element reporter was studied in this work.By using peptide-mediated affinity labeling technology,a short chain DNA was specifically labeled to immunoglobulin G(IgG)antibody K248,and then DNA base complementary pairing was used to realize accurate assembly of monoclonal antibodies and Eu-modified phage MS2 capsid,resulting in the preparation of highly sensitive and selective element tags.This method overcame the heterogeneity problem of element tags caused by random coupling,and ensured the targeting specificity,affinity and signal amplification ability of element tags.The element tag prepared here showed a specificity to bind/label with epidermal growth factor receptor(EGFR)biomarker on the surface of cancer cells,realizing single cancer cell analysis using ICP-MS.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.