Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

Objective To investigate the effect of esketamine on postoperative anxiety and cognitive function in gynecological malignant tumor patients with preoperative anxiety and cognitive decline.Methods Eighty-nine patients were selected for resection of gynecological malignant tumors,aged 18-64 years,BMI 18-28 kg/m2,ASA physical status Ⅱ or Ⅲ,the hospital anxiety and depression scale(HADS)anxiety subscale score≥8 points and montreal cognitive rating scale(MoCA)＜26 points 1 day before surgery.The patients were divided into two groups using the random number table method:the esket-amine group(group S,n = 45)and the normal saline group(group C,n = 44).In group S,esketamine 0.2 mg/kg was injected intravenously during anesthesia induction,0.25 mg·kg-1·h-1 was injected by pump during anesthesia maintenance,and esketamine 100 mg was used in the postoperative analgesic pump.Group C was given the same volume of normal saline during anesthesia induction,maintenance and PCIA analgesia,and other medications were the same as those in group S.HADS and MoCA were used to evaluate patients'anxiety and cognitive function 1 day before surgery and the 1 day and 3 days after surgery.The con-centration of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),S100 calcium-binding protein(S100β),and brain-derived neurotrophic factor(BDNF)were detected 1 day before surgery and 3 days af-ter surgery.The intraoperative dosage of remifentanil,ephedrine use rate,Ramsay sedation score 10 minutes after admission to PACU,extubation time,the number of total and effective compressions of PCIA within 48 hours after surgery,postoperative remedial analgesia,and the occurrence of adverse reactions,such as hy-pertension,hypotension,nausea and vomiting,chill,dizziness,and fever within 48 hours after surgerywere recorded.Results Compared with group C,the incidence of anxiety were significantly reduced and MoCA cognitive score were increased 1 day and 3 days after surgery,the concentrations of TNF-α,IL-6,and S100β were significantly reduced,the concentration of BDNF was significantly increased,the dosage of remifentanil was significantly reduced,the sedation score of Ramsay was significantly increased,the number of total compressions and effective compressions of PCIA within 48 hours after surgery was significantly re-duced,and postoperative fever was significantly reduced in group S(P＜0.05).There were no statistically significant differences in ephedrine use rate,extubation time,postoperative remedial analgesia rate,the in-cidence of other adverse reactions,such as hypertension,hypotension,nausea and vomiting,chills and diz-ziness within 48 hours after surgery between the two groups.Conclusion Esketamine can decrease the con-centrations of inflammatory factors and reduce nerve damage,help relieve anxiety and cognitive function of patients with gynecological malignant tumors.

Platelet count is an important basis for clinical diagnosis and treatment decisions,and accurate platelet count can assist in making correct clinical diagnosis and taking effective treatment measures in clinical practice.The common detection methods for platelet counting were reviewed,including peripheral blood smear platelet estimation,sheath flow impedance,optical method,microscope digital imaging technology and flow cytometry indirect counting.The advantages and disadvantages and the application conditions of the above methods were analyzed,and the new detection technology of platelet count was introduced,it provides ideas for developing new platelet counting methods.

Objective:To investigate the effect and possible molecular mechanism of mannan-binding lectin-associated serine protease (MASP) 1 on the biological behavior of hepatocellular carcinoma(HCC) cells.Methods:From January 10 to October 25, 2022, 20 pairs of fresh liver cancer tissue and adjacent (3 cm from cancer tissue) normal tissue samples of patients who underwent hepatic cancer resection at the Affiliated Hospital of Nantong University were collected, and the expression of MASP1 was analyzed. From March 1, 2012 to May 20, 2017, the cancer tissue and adjacent (3 cm from cancer tissue) normal tissue samples of 67 patients with HCC were collected from the tissue sample bank of the Department of Pathology, the Affiliated Hospital of Nantong University and the correlation between the expression level of MASP1 and clinical data of patients with HCC were analyzed. Human hepatoma cells lines SK-Hep1 and Hep3B were cultured, and MASP1 overexpression and MASP1 knockdown cell lines were constructed. SK-Hep1 negative control group, SK-Hep1 MASP1 overexpression group, Hep3B negative control group and Hep3B MASP1 knockdown group were set up. The effect of MASP1 on the proliferation of HCC cells was detected by subcutaneous tumor transplantation experiment in nude mice. The effect of MASP1 on the expression of epithelial-mesenchymal transition related proteins (N-cadherin, matrix metalloproteinase 9(MMP9), and E-cadherin), and the effects of MASP1 on the expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway related proteins and their phosphorylation levels were detected by Western blotting. Independent sample- t test, paired- t test and chi-square test were used for statistical analysis. Results:The results of immunohistochemical staining of 20 pairs of fresh tissue samples showed that the expression level of MASP1 in liver cancer tissue was lower than that in adjacent normal tissue (3.73±1.03 vs. 6.76±1.46), and the difference was statistically significant ( t=16.97, P<0.001). The correlation analysis of MASP1 expression level and clinical data of 67 patients with HCC revealed that the expression level of MASP1 was related to vascular invasion of the tumor, and the difference was statistically significant( χ2=5.20, P=0.023). The subcutaneous tumor transplantation experiment in nude mice showed that the volume and weight of subcutaneous tumor of mice in SK-Hep1 MASP1 overexpression group were lower than those of the SK-Hep1 negative control group((165.42±149.08) mm 3vs. (260.42±179.78) mm 3, (0.13±0.12) g vs. (0.18±0.12) g), and the differences were statistically significant ( t=5.15 and 3.89, both P<0.05). The results of Western blotting showed that the expression levels of N-cadherin and MMP9 in SK-Hep1 MASP1 overexpression group were lower than those of SK-Hep1 negative control group, while the expression level of E-cadherin was higher than that of SK-Hep1 negative control group (0.73±0.01 vs. 1.02±0.02, 0.40±0.01 vs. 0.69±0.01, 0.91±0.02 vs. 0.78±0.02), and the differences were statistically significant ( t=24.23, 36.87 and 9.27, all P<0.001). The expression levels of N-cadherin and MMP9 in Hep3B MASP1 knockdown group were higher than those in Hep3B negative control group, and the expression levels of E-cadherin was lower than that in Hep3B negative control group (1.04±0.01 vs. 0.31±0.01, 0.54±0.02 vs. 0.04±0.01, 0.56±0.01 vs. 0.93±0.01), and the differences were statistically significant ( t=163.20, 53.16, 60.74, all P<0.001). The expression levels of phosphoinositide PI3K, phosphoinositide Akt, and phosphoinositide mTOR of SK-Hep1 MASP1 overexpression group were lower than those of SK-Hep1 negative control group (0.59±0.01 vs.1.02±0.01, 0.64±0.01 vs. 1.12±0.02, 0.10±0.01 vs. 1.05±0.02); the expression levels of phosphoinositide PI3K, phosphoinositide Akt, and phosphoinositide mTOR of Hep3B MASP1 knockdown group were higher than those of Hep3B negative control group (0.96±0.01 vs. 0.55±0.01, 0.99±0.01 vs. 0.38±0.01, 0.93±0.02 vs. 0.06±0.01), and the differences were statistically significant ( t=40.87, 40.91, 87.30, 44.17, 107.50, 67.28, all P<0.001). Conclusions:The expression level of MASP1 is low in HCC tissue, and is significantly correlated with the poor prognosis of HCC patients and the occurrence of tumor vascular invasion. MASP1 may affect the proliferation and migration of liver cancer cells by regulating the PI3K/Akt/mTOR signaling pathway, suggesting that MASP1 may become a key gene in the treatment of HCC.

Objective To investigate the value of non-contrast CT(NCCT)-based radiomics for identifying acute unilateral middle cerebral artery occlusion(MCAO)with negative hyperdense artery sign(HAS).Methods All 80 patients with acute unilateral MCAO confirmed by angiography(MR angiography[MRA]or CT angiography[CTA]or DSA)and presenting with negative NCCT presentation for HAS were enrolled from January 2015 to June 2023 in the Emergency Department of Stroke Center of Affiliated Hospital of Yangzhou university.On the NCCT images,the occluded segment of the middle cerebral artery on the affected side of each case and the corresponding segment of the vessel on the normal side were used as the regions of interest,and a total of 108 radiomic features were extracted.The least absolute shrinkage and selection operator(LASSO)was used to screen the key features,construct and calculate the radiomics score,and four imaging histology models,support vector machine(SVM),light gradient boosting machine(LightGBM),GradientBoosting and adaptive boosting(AdaBoost),were built respectively to predict MCAO.Predictive performance was evaluated by the area under the receiver operating characteristic curves,and comparisons between the modeled receiver operating characteristic curves were made using the Delong test.Finally,the value of the application of radiological modeling was assessed by clinical decision curve analysis(DCA).Results The NCCT images based on 160 vessels were finally screened for 6 key features,including skewness,energy,gray level size zone matrix(GLSZM)-gray uneven,GLSZM-low gray area emphasis,GLSZM-size area non-uniform standardization,GLSZM-area entropy.The area under the curve(AUC)of the SVM-test was 0.688(95％CI 0.497-0.878)with an accuracy of 0.688;the AUC of the LightGBM-test was 0.787(95％CI 0.620-0.955)with an accuracy of 0.781;the AUC of the GradientBoosting-test was 0.654(95％CI 0.457-0.852)with an accuracy of 0.688;the AUC of the AdaBoost-test was 0.707(95％CI 0.515-0.899)with an accuracy of 0.750.The Delong test showed a statistically significant difference between LightGBM-test and GradientBoosting-test(P=0.040),and no statistically significant difference in performance between the remaining models(all P＞0.05).DCA showed that the LightGBM-test performed better.Conclusion NCCT-based radiomics has good diagnostic efficacy for identifying acute unilateral MCAO with negative HAS,and this conclusion needs to be further verified by multi-center and large sample studies.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

Objective:To investigate the related factors of vertebral body height reloss after pedicle screw fixation of thoracolumbar fracture and to determe the optimum prediction point.Methods:A retrospective case control study was made on 215 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from January 2010 to December 2017. There were 155 males and 60 females，aged 21-80 years［（48.6±10.4）years］. According to Denis fracture classification，there were 73 patients with compression fractures（type A in 15 patients，type B in 51，type C in 7），135 burst fractures（type A in 28 patients，type B in 87，type C in 20）and flexion distraction fractures（type A in 4，type B in 2，type C in 1）. All patients were treated by pedicle screw fixation. Follow-up lasted for 12- 48 months［（23.8±8.2）months］. Vertebral body height loss occurred in 86 patients（loss group），but did not in 129 patients（non-loss group）. The two groups were compared concerning sex，age，osteoporosis self-assessment tool for Asians（OSTA），body mass index（BMI），fracture types，number of fractured vertebrae，preoperative sagittal Cobb angle，preoperative degree of vertebral compression，number of screws placed in injured vertebrae，extent of vertebral reset and other related factors. Univariate analysis was used to identify the correlation of those factors with vertebral body height reloss. Multivariate Logistic regression analysis was performed to identify the independent factors for the height reloss with the receiver operating characteristic curve（ROC）and area under the curve（AUC）calculated to evaluate the optimum point in prediction of vertebral height reloss.Results:The two groups showed no significant differences in sex，age，BMI，fracture types，number of injured vertebrae，preoperative sagittal Cobb angle and number of screws placed in injured vertebrae（ P>0.05），but the differences were statistically significant in OSTA，preoperative degree of vertebral compression and extent of vertebral reset（ P<0.05）. According to the univariate analysis，OSTA，preoperative degree of vertebral compression and extent of vertebral reset were significantly correlated with the occurrence of vertebral body height reloss（ P<0.05）. According to the multivariate Logistic regression，OSTA（ OR=1.109，95% CI 0.527-0.685， P<0.05）and preoperative degree of vertebral compression（ OR =0.038，95% CI 0.539-0.689， P<0.05）were significantly related to vertebral body height reloss. The AUC relating OSTA and preoperative degree of vertebral compression to vertebral body height reloss was 0.604 and 0.614，respectively. The optimum prediction point of OSTA and preoperative degree of vertebral compression for vertebral body height reloss was 1.9 and 31.3%，respectively. Conclusions:OSTA and the preoperative degree of vertebral compression are independent risk factors for vertebral body height reloss. OSTA≤1.9 or preoperative degree of vertebral compression ≥31.3% indicates a significantly higher risk of postoperative vertebral body height reloss.

Objective To systematically review the clinical efficacy and safety of early use of recombinant human erythropoietin (rHu-EPO) for neuroprotection in premature infants.Method From establishment of the databases to November 2017,clinical randomized controlled trials (RCTs) of early use of rHu-EPO in premature infants were searched on English databases (PubMed,Embase,Cochrane Collaboration) and Chinese databases (CNKI,SinoMed,Wanfang,and VIP Database).Patients receiving conventional therapy were assigned into control group,and patients receiving both conventional therapy and rHu-EPO were assigned into rHu-EPO group.rHu-EPO group was subdivided into high-dose continuous group and low-dose intermittent group.We retrieved the related literatures,evaluated the quality,and then performed Meta-analysis using RevMan 5.3 software.Result A total of 2 588 patients in 17 studies were included and analyzed.Compared with the control group,Meta-analysis showed that early use of rHu-EPO was more effective in improving NBNA scores at 40 weeks of corrected gestational age (cGA) (MD=2.46,95％CI 1.58～3.33,P＜0.001),and high-dose continuous group was better than low-dose intermittent group (MD=3.19,95％CI 0.45～5.93,P=0.002;MD=2.22,95％CI 1.29～3.16,P＜0.001).Low-dose intermittent use of rHu-EPO significantly increased mental development index (MDI) (MD=6.66,95％CI 0.80～12.51,P=0.010) and psychomotor development index (PDI) (MD=5.77,95％CI 4.00～7.55,P＜0.001),and reduced the incidence of MDI＜70 at cGA 18～22 months (OR=0.42,95％CI 0.27～0.67,P＜0.001).As to the safety and side effects,treatment with rHu-EPO reduced the risk of necrotizing enterocolitis (OR=0.48,95％CI 0.31 ～0.72,P＜0.001) and periventricular leukomalacia (OR=0.52,95％CI 0.35～0.75,P＜0.001)without increasing the risk of bronchial dysplasia,patent ductus arteriosus,retinopathy in prematurity and intraventricular hemorrhage.Conclusion Current evidence shows that the early use of rHu-EPO in premature infants is relatively effective and safe,but multi-center RCTs are still needed.

Clinical data of a 33-year-old rheumatoid arthritis patient accompanied with pregnancy and lactation-associated osteoporosis(PLO) was retrospectively reviewed.The patient had two pregnancies within three years,and bone pain occurred during lactation of the second pregnancy after 2 months of delivery.Dual-energy X-ray (DEXA) showed decreased bone density,while thoracolumbar spine and pelvic X-ray film suggested osteoporosis.Her rheumatoid arthritis was stable and previous treatment did not include glucocorticoids.Other causes of metabolic bone diseases were excluded and the diagnosis of PLO was confirmed.The breastfeeding was stopped;calcium,active vitamin D,alendronate sodium were administrated,and the treatment was effective.Domestic and international literature from January 2000 to January 2019 was searched and no cases of PLO accompanied with rheumatoid arthritis were reported.There were only 100 cases of PLO retrieved in the literature,including 19 cases of PLO in China reported by four articles.It is suggested that PLO should be considered in RA patients presenting with arthragia during the lactation,in addition to relapse of disease.Awareness of PLO should be increased in physicians,especially rheumatologists,and anti-osteoporosis therapy is effective in patients with PLO.