Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-β(TGF-β), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1β in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-β, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-β/Smad4 signaling pathway.
Mice ; Male ; Animals ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Olive Oil/therapeutic use* ; Carbon Tetrachloride/metabolism* ; Liver Cirrhosis/metabolism* ; Liver ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/metabolism*

Objective: To study the expression and effect of small nuclear ribonucleoprotein-associated protein B (SNRPB) on proliferation and metastasis of liver cancer tissues and cells. Methods: The bioinformatics database starBase v3.0 and GEPIA were used to analyze the expression of SNRPB in liver cancer tissue and normal liver tissue, as well as the survival and prognosis of liver cancer patients. The expression of SNRPB mRNA and protein in liver cancer cell lines were analyzed by qRT-PCR and Western blot. RNA interference technique (siRNA) was used to determine SNRPB protein expression down-regulation. The proliferation effect on hepatocellular carcinoma cells was observed by MTT assay. Transwell invasion and migration assay was used to detect the changes in the metastatic ability of liver cancer cells after SNRPB down-regulation. Western blot was used to detect the changes of epithelial mesenchymal transition (EMT) markers in liver cancer cells after down-regulation of SNRPB expression. Data were compared between two groups and multiple groups using t-test and analysis of variance. Results: The expression of SNRPB was significantly higher in liver cancer tissue than normal liver tissue, and its expression level was correlated with the prognosis of liver cancer patients. Compared with the immortalized hepatocyte LO(2), the expression of SNRPB was significantly increased in the liver cancer cells (P < 0.01). siRNA-SNRPB had significantly inhibited the expression of SNRPB mRNA and protein in liver cancer cells. MTT results showed that the absorbance value was lower in SNRPB knockdown group than negative control group, and the difference at 96 h after transfection was most significant (P < 0.01). Transwell assay results showed that compared with the negative control group, the SNRPB knockdown group (MHCC-97H: 121.27 ± 8.12 vs. 46.38 ± 7.54; Huh7: 126.50 ± 6.98 vs. 41.10 ± 8.01) invasion and migration (MHCC-97H: 125.20 ± 4.77 vs. 43.18 ± 7.32; Huh7: 132.22 ± 8.21 vs. 38.00 ± 6.78) ability was significantly reduced (P < 0.01) in liver cancer cells. Western blot showed that the expression level of epithelial phenotype marker E-cadherin was decreased after down-regulation of SNRPB, while the expression levels of mesenchymal phenotype markers N-cadherin and vimentin was increased, suggesting that down-regulation of SNRPB inhibited EMT in liver cancer cells. Conclusion: SNRPB expression is significantly increased in liver cancer tissues and cells, and it is involved in regulating the proliferation, metastasis and EMT of liver cancer cells.
Carcinoma, Hepatocellular/genetics* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms/genetics* ; snRNP Core Proteins

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective: Total mesorectal excision (TME) is the gold standard for surgical treatment of mid-low rectal cancer, but the postoperative incidence of urination and sexual dysfunction is relatively high. Preserving the Denonvilliers fascia (DF) during TME can reduce the postoperative incidence of urination and sexual dysfunction. In this study, high resolution magnetic resonance imaging (MRI) was used to observe the imaging performance and display of DF, so as to determine the value of this technique in preoperative evaluation of the preservation of DF. Methods: A descriptive cohort study was carried out. Clinical data of patients with rectal cancer who underwent TME and received preoperative high-resolution MRI at department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University from August 2015 to June 2017 were retrospectively analyzed. The characteristics of DF were examined, and the shortest distance (d) between the anterior edge of tumor and DF was measured on high-resolution MRI. The distance d was compared between patients with stage T1-T2 and those with stage T3. Receiver operating characteristic (ROC) analysis was used to determine the predictive value of d for stage T1-T2 disease. Results: Thirty-two patients were enrolled in the study, including 27 males and 5 females with mean age of (62.9±8.9) years. DF was visualized in 96.9% (31/32) of cases on the T2WI sequence. The mean distance d in patients with stage T1-T2 disease (n=23) was (6.73±2.65) mm, and in those with stage T3 disease (n=9) was (1.30±1.15) mm (t=5.893, P<0.001). A cutoff of d >3 mm yielded specificity and positive predictive value for diagnosing stage T1-T2 disease of both 100%, sensitivity of 95.7% and negative predictive value of 90%. The optimum threshold of d was >3.05 mm, and Youden index was 0.957. Conclusions: High-resolution MRI can show the DF and accurately evaluate the relationship of DF with tumor in rectal cancer patients. Analysis on d value can provide an objective basis for the safe preservation of DF.
Aged ; Cohort Studies ; Fascia/pathology* ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Staging ; Rectal Neoplasms/surgery* ; Retrospective Studies

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity