Objective To establish an intelligent detection algorithm model for acute promyelocytic leukemia(M3 model)based on a contrast large model using machine learning statistical software and validate its effectiveness.Methods The data from 8 256 outpa-tients and inpatients who underwent complete blood cell analysis at Peking Union Medical College Hospital were retrieved and analyzed using the laboratory information system(LIS)and hospital information system(HIS).A M3 screening model was established and vali-dated using the data from outpatients and inpatients who underwent complete blood cell analysis at our hospital from July to October 2023.Results The M3 model demonstrated potential application value in screening for M3 disease in complete blood cell analysis,which showed certain efficacy in screening for neutrophil toxicity changes,particularly in identifying two cases of blue-green inclusion bodies in neutrophils.Conclusion The M3 model exhibited low specificity for M3 diagnosis.Future research should focus on increas-ing the number of M3-positive cases to optimize the model,ensuring high sensitivity while improving specificity.This model will provide assistance for the intelligent review of complete blood cell analysis.

Ado-trastuzumab emtansine (T-DM1) is a conjugate of trastuzumab and emtansine, which is one of the options for adjuvant therapy of residual invasive lesions after neoadjuvant therapy and rescue treatment of advanced breast cancer in patients with human epidermal growth factor receprot 2(HER2) mutation. Thrombocytopenia is one of the common adverse reactions of T-DM1. The incidence of all grade of thrombocytopenia was 3.6%-38.2%, and the incidence of grade 3 and above of thrombocytopenia was 0.4%-14.3% during treatment. The risk of thrombocytopenia is higher in Asian populations, patients with prior therapy of platinum, and those with a baseline platelet count of ≤200×10 9/L. The mechanism of thrombocytopenia caused by T-DM1 is not clear. Attention should be paid to monitoring platelet count during treatment, and patients with thrombocytopenia should be treated according to the severity.

Ado-trastuzumab emtansine (T-DM1) is a conjugate of trastuzumab and emtansine, which is one of the options for adjuvant therapy of residual invasive lesions after neoadjuvant therapy and rescue treatment of advanced breast cancer in patients with human epidermal growth factor receprot 2(HER2) mutation. Thrombocytopenia is one of the common adverse reactions of T-DM1. The incidence of all grade of thrombocytopenia was 3.6%-38.2%, and the incidence of grade 3 and above of thrombocytopenia was 0.4%-14.3% during treatment. The risk of thrombocytopenia is higher in Asian populations, patients with prior therapy of platinum, and those with a baseline platelet count of ≤200×10 9/L. The mechanism of thrombocytopenia caused by T-DM1 is not clear. Attention should be paid to monitoring platelet count during treatment, and patients with thrombocytopenia should be treated according to the severity.

Background::As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.Methods::Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.Results::Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera ( Enterobacter and Enterococcus) are unaffected by rifaximin therapy. Conclusions::IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration::Chinese Clinical Trial Registry, ChiCTR1800017911.

Myostatin gene (MSTN) encodes a negative regulator for controlling skeletal muscle growth in animals. In this study, MSTN^-/- homozygous mutants with "double muscle" phenotypic traits and stable inheritance were bred on the basis of MSTN gene editing rabbits, with the aim to establish a method for breeding homozygous progeny from primary MSTN biallelic mutant rabbits. MSTN^-/- primary mutant rabbits were generated by CRISPR/Cas9 gene editing technology. The primary mutant rabbits were mated with wild type rabbits to produce F1 rabbits, whereas the F2 generation homozygous rabbits were bred by half-sibling mating or backcrossing with F1 generation rabbits of the same mutant strain. Sequence analysis of PCR products and its T vector cloning were used to screen homozygous rabbits. The MSTN mutant rabbits with 14-19 week-old were weighed and the difference of gluteus maximus tissue sections and muscle fiber cross-sectional area were calculated and analyzed. Five primary rabbits with MSTN gene mutation were obtained, among which three were used for homozygous breeding. A total of 15 homozygous rabbits (5 types of mutants) were obtained (M2-a: 3; M2-b: 2; M3-a: 2; M7-a: 6; M7-b: 2). The body weight of MSTN^-/- homozygous mutant rabbits aged 14-19 weeks were significantly higher than that of MSTN^+/+ wild-type rabbits of the same age ((2 718±120) g vs. (1 969±53) g, P < 0.01, a 38.0% increase). The mean cross sections of gluteus maximus muscle fiber in homozygous mutant rabbits were not only significantly higher than that of wild type rabbits ((3 512.2±439.2) μm² vs. (1 274.8±327.3) μm², P < 0.01), but also significantly higher than that of MSTN^+/- hemizygous rabbits ((3 512.2±439.2) μm² vs. (2 610.4±604.4) μm², P < 0.05). In summary, five homozygous mutants rabbits of MSTN^-/- gene were successfully bred, which showed a clear lean phenotype. The results showed that the primary breeds were non-chimeric mutant rabbits, and the mutant traits could be inherited from the offspring. MSTN^-/- homozygous mutant rabbits of F2 generation could be obtained from F1 hemizygous rabbits by inbreeding or backcrossing. The progenies of the primary biallelic mutant rabbits were separated into two single-allelic mutants, both of which showed a "double-muscle" phenotype. Thus, this study has made progress in breeding high-quality livestock breeds with gene editing technology.
Animals ; CRISPR-Cas Systems/genetics* ; Gene Editing ; Muscle, Skeletal/metabolism* ; Mutation ; Myostatin/metabolism* ; Phenotype ; Rabbits

Objective To compare the MRI features of focal nodular hyperplasia (FNH) and inflammatory hepatocellular adenoma (Ⅰ-HCA),with an aim to improve the diagnostic accuracy in the two lesions.Methods Patients who underwent dynamic-enhanced MRI with histopathologically confirmed FNHs (21 patients with 21 tumors) and Ⅰ-HCAs (10 patients with 12 tumors) were included in this retrospective study.The clinical and the imaging features,including the T2-and T1-weighted,diffusion weighted images,and the dynamic enhanced imagings were analyzed.Results No significant difference was observed in the clinical data between the 2 groups of patients,except in the serum levels of C-reactive protein.The serum C-reactive protein levels were significantly elevated in Ⅰ-HCA than in FNH.Significant differences between patients with FNHs and Ⅰ-HCAs were also found in the morphologic findings and the signal intensities (including shape,centre scar,necrosis,signal intensity of T2WI and DWI,and lesion signal intensity compared to those of the liver in the portal venous phase and delayed phase).The differences in lesion to liver signal in FNH were significantly lower than those in Ⅰ-HCA in the T2WI and the delayed phases.The area under the curve (AUC) for the 2 groups of patients were 0.843 and 0.743,respectively,with no significant difference between them.Conclusions The MRI appearances of atypical FNHs overlapped with Ⅰ-HCA.MRI features of isointensity on T2 Wl and DWI,and isointensity to the liver in the delayed phase were valuable to differentiate FNHs from Ⅰ-HCAs.Most Ⅰ-HCAs showed moderate and marked high signal intensity on T2WI and DWI.These features,when combined with an elevated serum C-reaction protein,necrosis in the lesion and hyperintensity in the delayed phase,were valuable in differentiating Ⅰ-HCAs from FNH.

Objective: To investigate the diagnostic value of extracellular volume (ECV) imaging by magnetic resonance imaging for liver fibrosis of hepatitis B. Methods: A retrospective analysis was recruited in patients with chronic hepatitis B, who underwent liver surgery from April to October 2017 for pathological evaluation of liver tissues, and all patients underwent Gd-EOB-DTPA-enhanced T1 mapping to calculate the liver ECV score. The correlation between ECV and staging of hepatic fibrosis and inflammatory activity were compared to clarify the diagnostic value of staging of fibrosis. Results: 66 patients were enrolled in this study. Concerning the staging of liver fibrosis, there were 13, 4, 13, 10, and 26 cases with F0, F1, F2, F3 and F4 stages, respectively. ECV values had high interobserver consistency (correlation coefficient 0.860). The ECV difference between different stages of liver fibrosis was statistically significant (F = 15.02, P < 0.001). There was a significant positive correlation between ECV and fibrosis stage (r = 0.622, P < 0.001), and weak correlation with inflammatory activity (r = 0.332, P = 0.007). Fibrosis staging was an independent factor influencing ECV (P < 0.001). The area under the receiver operator characteristic curve for the diagnosis of liver fibrosis staging F≥1, F≥3 and F4 were 0.760, 0.846 and 0.873, respectively. The diagnostic sensitivity and specificity were 64.15%, 92.31%, 77.78%, 80.00% and 88.46, 72.50%, respectively. Conclusion MRI-ECV imaging has great value for staging hepatic fibrosis of hepatitis B, and it can provide an effective method for diagnosis, staging, and evaluating the curative effect of fibrosis.

Objective To investigate the diagnostic value of diffusion kurtosis imaging(DKI)in the classification of hepatic fibrosis. Methods Thirty-five male SD rats were randomly divided into two groups:the hepatic fibrosis group(n=28)and the control group(n=7). The rats in hepatic fibrosis group were randomly divided into 4 subgroups and seven rats per group, the rats were administrated 50％ CCl4 intraperitoneally twice a week to establish hepatic fibrosis , and the four subgroups were injected 2, 4, 6, and 8 weeks, respectively. The rats in the control group were administrated same dose of olive oil for 8 weeks. One rat in hepatic fibrosis group was died of liver failure in the 7th week, and a total of 27 fibrosis experimental rats and 7 control rats were finally included in this study. DKI was performed at the end of the injection period for all rats, the apparent diffusion(D)and kurtosis(K)values were evaluated. Rats were sacrificed immediately after MRI scan and liver specimens were collected. The liver tissues were examined by pathology, liver fibrosis degree, which was graded from S0 to S4, and inflammatory activity, which was graded from G0 to G3 were graded. The difference of D value and K value between different liver fibrosis and inflammatory activity scores was compared by one-way ANOVA(normal distribution)or Kruskal-Wallis test(skewed distribution). Spearman correlation analysis and multiple regression analysis were used to reveal the correlation between DKI parameters and fibrosis staging/necroinflammatory activity grade. To confirm the efficiency of using the ROC curve of DKI parameters to qualify the liver fibrosis grade, which grade was≥3. Results Seven, 6, 6, 7, 8 rats were diagnosed as S0 to S4, respectively. The difference of D value and K value among different fibrosis grades was statistically significant(P<0.05). D value and the degree of fibrosis was negatively correlated(r=-0.650, P<0.01);K value and liver fibrosis grade no correlation(r=0.336, P=0.080). Thirteen, 6, 8, 7 rats were diagnosed as G0 to G3, respectively. D value was negatively correlated with inflammatory activity(r=-0.590, P=0.001);K value was no correlation with inflammatory activity(r=0.169, P=0.389). Compared with inflammatory activity, fibrosis classification was an independent factor in determining D values(P=0.001). ROC analyses demonstrated an area under the curve(AUC)of D value, K value, D value combined with K value in the diagnosis of liver fibrosis grading ≥ 3 level were 0.781, 0.672 and 0.833, respectlively. The sensitivity and specificity of D value combined with K value were 83.3％ and 75.0％, respectively. Conclusion DKI imaging is of great value in the classification of hepatic fibrosis and can be used as an effective method for the diagnosis of fibrosis.

Objective To investigate the MRI findings of combined hepatocellular cholangio-carcinoma(cHCC-CC)and their correlation with pathologic types. Methods Twenty-nine patients with surgical pathology-confirmed cHCC-CC(20 patients with 24 cHCC-CCs were categorized as classical, and 9 patients with 10 cHCC-CCs as subtypes with stem cell features)were retrospectively analyzed. The clinical features, morphological and MRI signal characteristics on T1WI, T2WI, dynamic enhancement patterns and diffusion-weighted imaging were evaluated in detail and compared these imaging findings with pathologic types. The ADC values of 17 patients with 24 cHCC-CCs were measured. The imaging features were compared by using t test and Fisher test. Results The average maximum diameter of classical type and stem cell feature type were (3.8 ± 2.5) cm and (4.5 ± 1.8) cm, respectively, there was no significant difference(t=0.749,P=0.462). Seven cHCC-CCs showed heterogeneously high signal and twenty-seven cHCC-CCs showed low signal on T1WI. Seventeen cHCC-CCs showed hypointense in the central with mixed high and low signal on T2WI. Twenty-one cHCC-CCs showed peripheral enhancement and 13 lesions showed heterogeneously enhancement during arterial phase. The enhancement pattern of quickly wash-in and quickly wash-out were seen in 17 lesions, the other 17 lesions showed reversal enhancement. Twenty-five lesions presented with pseucapsule. There was no significant difference in clinical features and MRI findings between the two pathologic tumor types(classical type versus stem cell feature type)except for the enhancement pattern in arterial phase and peri-tumoral bile duct dilatation(P<0.05).The mean ADC value of the tumors with stem cell feature type(1.41 ± 0.52) × 10-3mm2/s was mildly lower than that of classical type (1.60 ± 0.39) × 10-3mm2/s, and no statistical differences were found(t=-1.005,P=0.326). Conclusions The MRI findings of cHCC-CCs has specificity. However, it is not easy to distinguish the classical type and stem cell feature type of cHCC-CC only by MRI findings.

Objective To investigate the MRI findings of combined hepatocellular cholangio-carcinoma(cHCC-CC)and their correlation with pathologic types. Methods Twenty-nine patients with surgical pathology-confirmed cHCC-CC(20 patients with 24 cHCC-CCs were categorized as classical, and 9 patients with 10 cHCC-CCs as subtypes with stem cell features)were retrospectively analyzed. The clinical features, morphological and MRI signal characteristics on T1WI, T2WI, dynamic enhancement patterns and diffusion-weighted imaging were evaluated in detail and compared these imaging findings with pathologic types. The ADC values of 17 patients with 24 cHCC-CCs were measured. The imaging features were compared by using t test and Fisher test. Results The average maximum diameter of classical type and stem cell feature type were (3.8 ± 2.5) cm and (4.5 ± 1.8) cm, respectively, there was no significant difference(t=0.749,P=0.462). Seven cHCC-CCs showed heterogeneously high signal and twenty-seven cHCC-CCs showed low signal on T1WI. Seventeen cHCC-CCs showed hypointense in the central with mixed high and low signal on T2WI. Twenty-one cHCC-CCs showed peripheral enhancement and 13 lesions showed heterogeneously enhancement during arterial phase. The enhancement pattern of quickly wash-in and quickly wash-out were seen in 17 lesions, the other 17 lesions showed reversal enhancement. Twenty-five lesions presented with pseucapsule. There was no significant difference in clinical features and MRI findings between the two pathologic tumor types(classical type versus stem cell feature type)except for the enhancement pattern in arterial phase and peri-tumoral bile duct dilatation(P<0.05).The mean ADC value of the tumors with stem cell feature type(1.41 ± 0.52) × 10-3mm2/s was mildly lower than that of classical type (1.60 ± 0.39) × 10-3mm2/s, and no statistical differences were found(t=-1.005,P=0.326). Conclusions The MRI findings of cHCC-CCs has specificity. However, it is not easy to distinguish the classical type and stem cell feature type of cHCC-CC only by MRI findings.