Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2～3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26％ and the specificity was 83.82％.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.

Objective:To investigate the application value of enhanced recovery after surgery (ERAS) in perioperative period of laparoscopic sleeve gastrectomy (LSG).Method:The retrospective cohort study was conducted. The clinical data of 1 181 patients undergoing LSG in the Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine from January 2021 to December 2023 were collected. There were 242 males and 939 females, aged (31±8)years. Of 1 181 patients, 598 cases receiving routine perioperative care were divided into the control group, and 583 cases receiving perioperative care with ERAS were divided into the ERAS group. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between the groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney rank sum test was used for comparison between the groups. Count data were expressed as absolute numbers or percentages, and the chi-square test or Fisher exact probability were used for comparison between the groups. Repeated measurement data were analyzed using the repeated ANOVA, with baseline scores as covariates. Simple effects analysis was conducted in case of interaction, and multiple comparisons were adjusted using the Bonferroni method. Results:(1) Postoperative outcomes. The numerical rating scale (NRS) scores for pain at immediate return to the ward and on the third postoperative mornings changed from 5.35±0.93 to 2.57±0.83 in the control group, versus changed from 3.15±0.93 to 0.70±0.65 in the ERAS group, showing significant difference between the two groups ( Ftime=66.58, Fgroup=1 765.85, Finteraction=6.90, P<0.05). After adjusting NRS scores for pain at immediate return to the ward as the baseline, results of simple effects analysis showed that on the third postoperative mornings, the NRS scores in the ERAS group were lower by 1.89, 1.53, and 1.76 respectively compared to the control group ( P<0.05). Cases with nausea at immediate return to the ward and on the third postoperative mornings changed from 497 to 97 in the control group, versus changed from 198 to 11 in the ERAS group, showing signifi-cant difference between the two groups ( χ2=294.45, 398.76,209.39, 73.00, P<0.05). Cases with vomiting at immediate return to the ward and on the third postoperative mornings changed from 243 to 41 in the control group, versus changed from 51 to 2 in the ERAS group, showing significant difference between the two groups ( χ2=160.54, 149.37, 71.76, 35.69, P<0.05). The duration of postoperative hospital stay was (3.22±0.65)days in the control group, versus (2.17±0.49)days in the ERAS group, showing a significant difference between the two groups ( t=-11.89, P<0.05). (2) Complications. The incidence of cases with dehydration within postoperative 30 days was 0.50%(3/598) in the control group, versus 0.69%(4/583) in the ERAS group, showing no significant difference between the two groups ( P>0.05). None of patient in the control group and the ERAS group experienced bleeding, gastric leakage, intra-abdominal infection, and no patient had unplanned secondary surgery within postoperative 30 days. Conclusions:ERAS in perioperative period of LSG are safe and feasible. Compared to routine care, ERAS can significantly reduce postoperative pain, decrease the incidence of postoperative nausea and vomiting, shorten the postoperative hospital stay, and do not increase the rate of postoperative complications or unplanned secondary surgeries within postoperative 30 days.

Objective To investigate the effect of intestinal Metrnl on dextran sodium sulfate (DSS)-induced ulcerative colitis mouse model and the regulation mechanism of intestinal microbiota. Methods Different concentrations of DSS (3% DSS and 1% DSS) were used to induce ulcerative colitis on C57 mice to determine the experimental conditions. Intestinal epithelial Metrnl specific knockout mice (Metrnl^(-/-)) and its control mice (Metrnl^(+/+)) were administrated with 3% DSS for 5 d. Then the survival time, body weight, DAI (disease activity index), colon length and pathological changes in colon tissues were observed. 16S ribosomal RNA gene sequencing was used to detect the composition of intestinal microbiota. Results Compared with 1% DSS, 3% DSS could significantly aggravate ulcerative colitis on C57 mice, such as lower survival rate (P<0.05), more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). After administrated to 3% DSS for 5 d, comparing with Metrnl^(+/+) mice, Metrnl^(-/-) mice showed more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). The 16S ribosomal RNA results showed that the diversity of intestinal microbiota in Metrnl^(-/-) mice significantly decreased. Furthermore, Bacteroidetes and Proteobacteria significantly decreased, while Firmicutes increased. Conclusion Metrnl could protect the DSS-induced ulcerative colitis mouse through regulating intestinal microbiota.

RNA ; CRISPR-Cas Systems

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

As medical research progresses, an increasing number of genetic variations are being incorporated into international guidelines for the diagnosis and treatment of hematological malignancies. In several international guidelines updated in 2022, more emphasis is placed on the importance of genetic variation in the classification and prognosis assessment of hematological malignancies. The clinical diagnosis and treatment of hematological malignancies have entered the era of precision medicine and genomics, relying increasingly on the application of high-throughput sequencing technology.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics* ; Epigenesis, Genetic ; Fanconi Anemia/genetics* ; Germ Cells ; Hematologic Neoplasms/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Retrospective Studies

Objective:To establish a set of scientific and reasonable indicator system of common prosperity in the field of health, so as to promote the construction and evaluation of the demonstration area of common prosperity with high quality of health.Methods:According to the requirements of promoting common prosperity demonstration area with high quality of health in Zhejiang province, the initial indicator pool was established through literature research and theoretical analysis in July 2021, and experts were convened to carry out expert brainstorming to determine indicator system in the form of meetings. Delphi method was used to conduct two rounds of expert consultation on the indicator system.Finally, the analytic hierarchy process and percentage weight method were used to calculate the indicator weight value.Results:The final indicator system included 4 first-level indicators and 30 second-level indicators. Among the first-level indicators, the weight values of the development, equilibrium, inclusiveness, and sustainability were 0.326 4, 0.242 8, 0.245 8, and 0.185 0. There were 8 second-level indicators in developmental indicator dimension, of which the indicator with the highest weight was the per capita health expectancy. The balance indicator dimension included 6 second-level indicators, of which the indicator with the highest weight was the per capita financing difference of basic medical insurance between the urban workers with the urban-rural residents. The inclusive indicator dimension included 6 second-level indicators, and the proportion of personal health expenditure to total health expenditure had the highest weight. The sustainability indicator dimension included 10 second-level indicators, and the proportion of government health expenditure in fiscal expenditure had the highest weight.Conclusions:The indicator system constructed in this research could provide certain guidance and reference for promoting the construction of common prosperity in health, and provide some reference for follow-up research in this field.

Objective:To explore the effect of a Chinese medicinal composition ( Xiadanqi) on the prevention of radon exposure induced injuries of lung in vitro and in vivo. Methods:Mice were randomly divided into three groups of blank control group, radon-exposed group alone and radon-exposed group intervened with Chinese medicinal composition. The pathological changes of lung tissues in each group after 120 WLM were observed by HE and Masson staining, and the expressions of α-SMA protein and Vimentin protein in lung tissues were detected by immunohistochemistry staining. The levels of oxidative stress in lung tissue of each group were detected with SOD and MDA kits. At the same time, a radon exposed cell model and a radon exposure + Xiadanqi intervention cell model were constructed using an ecological radon chamber. The cell adhesion abilities of different groups were detected by an adhesion kit. The cell migration ability of each group was determined by the transwell migration experiment. The expression of E-cadherin and Vimentin protein was detected by Western blot. Results:Compared with the radon exposure group, the concentration of MDA was decreased ( t=4.43, P<0.05), the activity of SOD was increased ( t=3.22, P<0.05), and α-SMA and Vimentin protein expressions were decreased ( t=3.08, 7.57, P<0.05) in lung tissue of mice intervened with 2 mg/g Xiadanqi. In vitro, compared with radon exposure group, the migration ability was reduced ( t=4.78, 13.01, P<0.05), the cell adhesion property was enhanced ( t=3.41, 12.55, P<0.05), the expression of E-cadherin protein was increased ( t=2.96, 19.57, P<0.05), and the expression of Vimentin protein was obviously reduced ( t=21.00, 33.32, P<0.05) in radon-exposed cells with the treatment of Chinese medicine (150 μg/ml and 200 μg/ml). Conclusions:The Chinese medicinal composition ( Xiadanqi) has a certain radioprotective effect on radon exposure induced injury by reducing oxidative stress, attenuating EMT and fibrosis, and thus it may be applied as a protective agent for radon induced injury.