Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

Objective: To explore the role of mobile phone addiction and anxiety symptoms in the relationship between childhood psychological abuse and depressive symptoms among college students, in order to provide a basis for mental health promotion. Methods: From February to May 2023, a stratified random sampling method was used to select 1 799 freshmen to juniors from a university in Wuhu City, Anhui Province. The questionnaire survey was conducted using the 2-item Patient Health Questionnaire (PHQ-2), Child Psychological Maltreatment Scale (CPMS), Mobile Phone Addiction Tendency Scale (MPATS), 2-item General Anxiety Disorder (GAD-2). Correlations among each variable were analyzed, and the chain mediating effect of mobile phone addiction and anxiety symptoms was explored. Results: The detection rate of depressive symptoms among college students was 9.7%, and the positive detection rate of childhood psychological abuse was 28.6%. Depressive symptoms were positively correlated with childhood psychological abuse, mobile phone addiction and anxiety symptoms ( r =0.28, 0.32, 0.27, P <0.01). Childhood psychological abuse was positively correlated with mobile phone addiction and anxiety symptoms ( r =0.29, 0.71, P <0.01). Mobile phone addiction and anxiety symptoms were positively correlated ( r =0.30, P <0.01). Childhood psychological abuse could effectively predict depressiove symptoms, mobile phone addiction and anxiety symptoms ( β =0.08, 0.06, 0.66, P <0.01). Mobile phone addiction and anxiety symptoms had a chain mediating effect between childhood psychological abuse and depression symptoms, with a total indirect mediating effect (effect=25.27%, P <0.05), accounting for 72.44% of the total effect. Conclusions Mobile phone addiction and anxiety symptoms play a chain mediating role between childhood psychological abuse and depressive symptoms. Focusing on childhood psychological abuse, mobile phone addiction and anxiety among college students are beneficial for depression symptoms prevention.

To investigate the cellular target selectivity of small molecules targeting thioredoxin reductase 1, we reported the construction and functional research of a stable TrxR1 gene (encode thioredoxin reductase 1) knockout HCT-116 cell line. We designed and selected TrxR1 knockout sites according to the TrxR1 gene sequence and CRISPR/Cas9 target designing principles. SgRNA oligos based on the selected TrxR1 knockout sites were obtained. Next, we constructed knockout plasmid by cloning the sgRNA into the pCasCMV-Puro-U6 vector. After transfection of the plasmid into HCT-116 cells, TrxR1 knockout HCT-116 cells were selected using puromycin resistance. The TrxR1 knockout efficiency was identified and verified by DNA sequencing, immunoblotting, TRFS-green fluorescent probe, and cellular TrxR1 enzyme activity detection. Finally, the correlation between TrxR1 expression and cellular effects of drugs specifically targeting TrxR1 was investigated by CCK-8 assay. The results demonstrated that the knockout plasmid expressing the sgRNA effectively knocked-out TrxR1 gene within HCT-116 cells, and no expression of TrxR1 protein could be observed in stable TrxR1 knockout HCT-116 (HCT116-TrxR1-KO) cells. The TrxR1-targeting inhibitor auranofin did not show any inhibitory activity against either cellular TrxR1 enzyme activity or cell proliferation. Based on these results, we conclude that a stable TrxR1 gene knockout HCT-116 cell line was obtained through CRISPR/Cas9 techniques, which may facilitate investigating the role of TrxR1 in various diseases.
CRISPR-Cas Systems/genetics* ; Gene Editing ; Gene Knockout Techniques ; HCT116 Cells ; Humans ; RNA, Guide/metabolism*

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death. Although great progress has been made in chemotherapy, radiotherapy and targeted therapy, the emergence of acquired drug resistance hinders the efficacy of clinical treatment. Studies have shown that tumor is a class of diseases with damaged cell cycle regulation mechanism, in which checkpoint kinase (Chk) plays a core role, Chk1 and Chk2 are very important protein kinases in the checkpoint. In recent years, it has been found that the regulation of Chk1 and Chk2 plays an important role in the clinical treatment and drug resistance mechanism of lung cancer. This article reviews the mechanism of cell cycle checkpoint kinase and drug resistance of lung cancer, and expounds the effective therapeutic targets and methods of lung cancer.
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Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.

Objective: To evaluate the efficacies of lopinavir/ritonavir and abidol in the treatment of NCP. Methods: The clinical data of 134 patients with NCP receiving treatment at Shanghai Public Health Clinical Center during Jan 20 to Feb 6, 2020 were retrospectively collected. All the patients received interferon-α2b spray and symptomatic supportive treatment, and 52 cases received oral lopinavir/ritonavir treatment, 34 cases received oral abidol treatment, the remaining 48 cases did not take any antiviral drugs. The efficacies at median day 7 among the three groups were compared by using Kruskal-Wallis or chi-square tests. Results: The 134 patients included 69 males (51.5%) and 65 females, aged 35-62 years with the average of 48 years. The median time to temperature normalization in patients receiving abidol or lopinavir/ritonavir treatment was both 6 days after admission, and that was 4 days in the control group, with no significant difference (χ²=2.37, P=0.31). The median time to PCR negative in the respiratory specimens in the three groups was all 7 days after admission, and the PCR negative rates at day 7 after admission in lopinavir/ritonavir, abidol and control groups were 71.8% (28/39), 82.6% (19/23) and 77.1% (27/35), respectively, which were not significantly different (χ²=0.46, P=0.79). Radiological worsening at day 7 was observed in comparable proportions of patients in the three groups, which were 42.3% (n=22), 35.3% (n=12) and 52.1% (n=25), respectively (χ²=2.38, P=0.30) . Adverse reactions occurred in 17.3% (n=9), 8.8% (n=3) and 8.3% (n=4) patients, respectively in the three groups (χ²=2.33, P=0.33). Conclusions This study did not find any effects of lopinavir/ritonavir and abidol on relieving symptoms or accelerating virus clearance. The efficacies of these two drugs in NCP treatment need further investigation.

Objective:To evaluate the efficacies of lopinavir/ritonavir and abidol in the treatment of novel covonavirus pneumonia (NCP).Methods:The clinical data of 134 patients with NCP receiving treatment at Shanghai Public Health Clinical Center during January 20 to February 6, 2020 were retrospectively collected. All the patients received interferon-α2b spray and symptomatic supportive treatment, and 52 cases received oral lopinavir/ritonavir treatment, 34 cases received oral abidol treatment, the remaining 48 cases did not take any antiviral drugs. The efficacies of the three groups were compared, and Chi-square test was used for statistical analysis.Results:The 134 patients included 69 males (51.5%) and 65 females (48.5%), aged 35 to 62 years with the average of 48 years. The median time to temperature normalization in patients receiving abidol or lopinavir/ritonavir treatment was both six days after admission, and that was four days in the control group, with no significant difference ( χ2=2.37, P=0.31). The median time for polymerase chain reaction (PCR) negative in the respiratory specimens in the three groups was all seven days after admission, and the PCR negative rates at day seven after admission in lopinavir/ritonavir, abidol and control groups were 71.8% (28/39), 82.6% (19/23) and 77.1% (27/35), respectively, which were not significantly different ( χ2=0.46, P=0.79). Radiological worsening at day seven was observed in comparable proportions of patients in the three groups, which were 42.3% (22/52), 35.3% (12/34) and 52.1% (25/48), respectively( χ2=2.38, P=0.30). Adverse reactions occurred in 17.3% (9/52), 8.8% (3/34) and 8.3% (4/48) patients, respectively in the three groups ( χ2=2.33, P=0.33). Conclusions:This study does not find any effects of lopinavir/ritonavir and abidol on relieving symptoms or accelerating virus clearance. The efficacies of these two drugs in NCP treatment need further investigation.

Objective To analyze the therapeutic effect and tolerability of decitabine monotherapy or combined with arsenic trioxide for the treatment of patients with myelodysplastic syndromes (MDS). Methods Clinical characteristics of 32 patients with primary MDS in North Hospital of Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University from January 2014 to April 2017 were retrospectively analyzed. The clinical data of these patients were collected, and the patients were followed up. Decitabine combined with arsenic trioxide was used in 23 cases, decitabine (20 mg·m-·2d-1) and arsenic trioxide (0.16 mg/kg) were administrated from day 1 to day 5 and was repeated every 4-6 weeks. For the remaining 9 cases, only decitabine was applied, decitabine(20 mg·m-2·d-1) was administrated from day 1 to day 5 and was repeated every 4-6 weeks. The clinicopathological characteristics and the effect of genetic mutations on the efficacy of treatment were investigated. Results Of the 32 patients with primary MDS, 18 were male and 14 were female. The patients were 17-72 years old with a median age of 56 years old. Genetic analysis revealed 10 cases with TP53 mutations, 8 cases with TET2 mutations, 4 cases with U2AF1 mutations, 3 cases with RUNX1 mutations, 3 cases with ASXL1 mutations, 2 cases with NRAS mutations, 2 cases with DNMT3A mutations and 1 case with JAK2 V617 mutation. The follow﹣up time was 2-23 months with a median follow﹣up time of 8 months. A total of 21 cases (65.6%) attained treatment response. Among them, there were 10 cases (31.3%) with complete remission (CR), 5 cases (15.6%) with bone marrow complete remission (MCR), and 6 cases (18.7%) with hematological improvement. There was no significant difference in the efficiency and CR rate between the combination group and the monotherapy group (P＝0.441, P＝0.681). Ten cases were found to have TP53 mutations, of which 7 cases had CR. Multivariate analysis demonstrated that TP53 mutation was an independent risk factor for CR (P＝ 0.037). All patients developed myelosuppression after treatment, of which 16 cases developed pulmonary infection. Conclusions Decitabine combined with arsenic trioxide in the treatment of MDS is effective and well tolerated. The therapeutic effects of decitabine monotherapy or decitabine combined with arsenic trioxide for treatment of patients with TP53 mutations are better than the average levels.

Objective To explore the influencing factors of career planning for nurses aged 30 to 40 years old. Methods Based on descriptive qualitative study, purposive sampling and the maximum variation strategy were used, nurses aged 30 to 40 years old who work at hospitals in Zhejiang province were selected as participants. Face-to-face semi-structured interviews were conducted focusing on influencing factors of career planning and field notes were written. Traditional content analysis was used for analyzing the data, and themes were extracted. The sample size was based on the criteria of saturation. Results A total of 12 participants were included. After analysis, the main influencing factors of career planning were identified: self- perception (such as their own personality, interests and expertise, professional ability, physical condition), knowledge of nursing work (including the cognition of nursing specialty and the nature of nurses' work), career development space (such as career development platform, career development path, career development bottleneck, learning and promotion opportunities), family factors (including family support and family outlook), hospital culture(including interpersonal relationships, leadership support, management style), career planning knowledge(including knowledge of career planning and guidance on career planning in work). Conclusions There are many factors influence career planning. Relevant departments and nursing managers should assist these nurses in making reasonable career planning according to their situation.