Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development

Objective:To improve the rate of successful rescue through analyzing the clinical features and treating processes of septic shock caused by lymphocyst infection after lymph node dissection in diabetic patients.Methods:A total of 462 cases of diabetic patients with bladder, prostate, renal cancers, cervical, endometrial and ovarian were retrospectively analyzed, all of whom underwent standard surgical treatments including pelvic lymph node dissection, hospitalized in department of urology surgery and gynecology of Sun Yat-sen Memorial Hospital from Jan 2015 to Jan 2020. Lymphocytes were confirmed in 148 cases, of which 89 cases were complicated by infection, and 13 cases developed septic shock. Patients with lymphocyst infection were divided into shock and non-shock groups, and age, sex, duration of diabetes, BMI, glycosylated hemoglobin at admission, number of lymph nodes surgically removed, retention time of drainage tube after operation, maximum diameter of lymphocyst and time between infection and previous chemotherapy were compared. The initial symptoms, blood routine in the first time after the onset of the infection, the time from onset to drainage puncture and catheterization and the final outcomes were analyzed in 13 patients with septic shock. The results of pathogen culture and drug sensitivity of infected lymphocyst fluid were also analyzed.Results:Categorical variable test showed that: in diabetic patients with lymphocyst infection, there were significant differences in glycosylated hemoglobin ( P=0.018) , adjuvant chemotherapy ( P=0.014) and lymphocyst size ( P<0.001) between shock group and non-shock group. Among the 13 cases of septic shock, 11 caseshad mild to moderate fever or abdominal pain. The total leukocyte count of all cases in the first hemogram were less than 20×10 9/L. The average time from onset to drainage was 33 hours. Among the 13 patients, 5 developed MODS and 1 died. There were 2 patients whose conditions were complex with frequent fluctuations. In the 12 patients who recovered from septic shock, only 1 underwent a residual lymphocyst pretreatment, 4 had recurrent cyst infection for 1-2 times, 2 had septic shock again, and 1 died. Gram negative bacteria were the most common pathogens, and the main was Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Piperacillin / tazobactam, carbapenems and tigecycline were commonly sensitive, while the drug resistance rates of ceftazidime, ceftriaxone and levofloxacin were more than 50%. Conclusions:Poor glycemic control, adjuvant chemotherapy and big lymphocyst size(d≥5 cm) are the high risk factors of septic shock. Most of shock patients' initial symptoms and total white blood cell count have no warning significance, leading to longer time from infection to drainage, and delayed treatment. Early diagnosis, timely drainage and active anti-infection treatment are the key to a successful treatment. The possibility of connection between lymphocyst and surrounding organ should be considered when the treatment effect is not good. After septic shock of postoperative lymphocyst infection in patients with diabetes, the larger esidual lymphocyst should be intervened actively to avoid serious infection again.

Objective: To explore the correlation between menopausal hormone therapy（MHT）and breast lesions in perimenopausal women,and to provide evidence for safe use of MHT. Methods: The 40-60 year-old women who visited Hangzhou Women's Hospital and met the diagnostic criteria for perimenopausal syndrome were recruited. The intervention group received MHT and was divided into three subgroups according to the MHT regimen：estrogen-progesterone cycle therapy（A）,estrogen-progesterone continuous therapy（B）,estrogen therapy（C）. The control group did not receive MHT. All the patients received regular mammography to quantify and evaluate breast lesions. The generalized estimating equation was used to analyze the changes of breast lesions between different groups. Results: There were 80 cases in the intervention group,with 49 in group A,26 in group B,5 in group C,and 80 cases in the control group. After two years of follow-up,there was no statistically significant differences of time,group and interaction in breast density,volume of breast fibrous tissue and the volume of breast between three intervention groups and the control group（P>0.05）; there was no statistically significant differences of group and interaction in positive rate of calcification and breast mass between the intervention group and the control group（P>0.05）. Conclusion Receiving MHT intervention for two years did not increase the risk of breast lesions.

Objective To investigate the effect of Zinc finger E-box binding homeobox protein 1 (ZEB1) on the radiosensitivity of gastric cancer cells AGS and its possible mechanism. Methods AGS cells were irradiated by X-rays at different doses (0, 2, 4, 6, and 8 Gy). Western blot was used to observe the expression of ZEB1 in cells. AGS cells, in logarithmic growth phase, were transfected with of ZEB1 gene or its interference plasmids, the corresponding control plasmids ( pcDNA3. 1 ) and negative control interference plasmids. They were classified as overexpression ZEB1 group, silencing ZEB1 group, control group and negative control group, respectively. The effect of overexpression and silencing ZEB1 on the survival of AGS cells after irradiation were analyzed by colony formation assay. The cell apoptosis rate was analyzed by flow cytometry. The expressions of histone H2A (H2AX), phosphorylated H2AX (γ-H2AX) and telangiectasia mutated gene (ATM) were detected by Western blot. Results The expression of ZEB1 in AGS cells was dependent on radiation dose (F=58. 57, P<0. 05). Overexpression of ZEB1 increased AGS cells viability, inhibitedγ-H2AX expression (t=12. 18, P<0. 05), blocked cell apoptosis (t=7. 27, P<0. 05) and up-regulated ATM expression in time-dependent manner after irradaition (F=165. 70, P <0. 05). Silencing ZEB1 reduced AGS cells viability, increased γ-H2AX expression ( t =12. 88, P<0. 05) and cell apoptosis (t =8. 36, P <0. 05), and down-regulated of ATM expression (F=44. 80, P<0. 05). Conclusions ZEB1 regulates the radiosensitivity of gastric cancer AGS cells by up-regulating ATM expression.

Objective To explore the effect of psychological nursing on anxiety and depression and quality of life of patients with multi drug resistant pulmonary tuberculosis.Methods 58 patients with multi -drug resistant pulmonary tuberculosis were randomly divided into observation group and control group,29 cases in each group.The control group received routine nursing care,the observation group received psychological nursing on the basis of the control group.Before and after psychological nursing intervention,the self rating anxiety scale(SAS)and depression self rating scale(SDS),health survey(SF -36)score were observed,and the clinical curative effect and compliance of the two groups were observed.Results After psychological nursing intervention,the SAS and SDS scores of the observation group[(36.83 ±7.61)points and (40.07 ±5.49)points]were significantly lower than the control group [(44.07 ±9.16)points and (43.90 ±7.91)points],the differences were statistically significant(t =3.27,2.14,all P <0.05).The SF -36 scores showed that after psychological nursing intervention,the physiological function(PF), physiological functions(RP),general health(GH),vitality(VT),social function(SF),role emotional(RE),mental health(MH),the seven dimensions scores of the observation group were significantly higher than those in the control group,the differences were statistically significant(t =7.18,10.22,8.85,12.71,12.04,9.68,4.79,all P <0.05). The compliance of the observation group was 93.10%,which of the control group was 72.41%,the difference was significant(χ2 =4.35,P <0.05).The total effective rate of the observation group was 86.21%,which of the control group was 62.07%,the difference was statistically significant(χ2 =4.41,P <0.05).Conclusion The psychological nursing intervention can improve the anxiety and depression of patients with multi -drug resistant tuberculosis, improve the quality of life of patients,improve the treatment compliance of patients,and improve the clinical efficacy.

Objective To investigate the effect of psychological nursing intervention on mental health and quality of life for stroke patients with depression and anxiety. Methods Totals of 89 stroke patients with depression and anxiety were randomly divided into the observation group and the control group. The control group ( 44 cases ) was given routine nursing method, while the observation group ( 45 cases ) was given psychological nursing care based on the control group. The mental status was evaluated by HAMD, SAS and SDS scale, and the quality of life was evaluated by WHO-QOLs. The recovery of nerve function, mental status, life and nursing quality between groups were compared. Results Before the nursing intervention, the neurologic impairment score, HAMD score, SAS score and SDS score between groups had no significant difference ( P>0. 05). After the nursing intervention, the above scores of the observation group was decreased significantly, and the score of quality of life ( psychological, physiological, environmental and social relationships ) of the observation group were significantly improved (P<0. 05). The nursing satisfaction rate of the observation group was 93. 33%, which was significantly higher than 70. 45% of the control group (χ2 =5. 13,P <0. 05). Conclusions The psychological nursing intervention can help patients improve mental health and quality of life.

To assess the effectiveness and safety ofinside-out (TVT-O) vs. outside-in transobturator-tape procedures (TOT) in the surgical management of female stress urinary incontinence (SUI).A total of 8 randomized controlled trials were retrieved from the literature and analyzed by metaanalysis with RevMan 5.0 software.Meta-analysis showed that no statistical differences existed in objective cure rate,objective failure,postoperative voiding dysfunction,groin/thigh pain and sling exposure in both procedures (P ＞ 0.05).These preliminary results suggest there is no evidence of significant differences in the efficacy and safety between TVT-O and TOT.

ObjectiveTo investigate distingwished clinical and experimental characteristics of the four main subtypes in myelodysplastic/myeloproliferative neoplasms (MDS/MPNs).MethodsMDS/MPNs 53 cases from Provincial Hospital Affiliated to Shandong University,including 24 cases CMML,13 cases aCML,12 cases JMML,4 cases MDS/MPN-U,were analyzed regarding to 2001 WHO classification.Morphology (M) of peripheral and bone marrow blood cells were observed under microscope.FCM was used in immunological(Ⅰ) analyse on blasts and myelomonocytes in peripheral blood and bone marrow.G-banding technique was used in cytogenetic (C)examination.PCR was used in molecular genetic (M) mutation detection.Numeric data,such as mean Hb,WBC,PLT et al,among several groups,were compared using Single-factor analysisof variance.Student-Newman-Keulstestwasuseincomparingmeansof two groups.Proportions,such as percentage of clinical features,immunological and cytogenetic abnormal cases among different groups,were compared using Chi-square test or Fisher exact test.Results( 1 ) In the course of MDS/MPNs,there were 46 cases (86.8％ ) had paleness and fatigue 33 cases (62.5％ ) had palpable spleen.JMML had most fever and enlargement of lymph node (75.0％,75.0％ ),statistically distinguished from CMML ( 12.5％,12.5％ ) (x2 =14.89,17.98,P ＜ 0.05 ).(2) The hemoglobin was ( 83.1 ± 24.6 ) g/L.WBC counts were ( 19.8 ± 8.1 ) × 109/L.PLT counts were ( 158.7 ± 108.2) x 109/L.Immature neutrophils and blasts were found in peripheral blood.(3)JMML and CMML had most monocytes absolute counts among the subtypes (4.25 ±0.76) (3.62 ±0.76).(4) Almost 100％ JMML had monocytes abnormalities.(5)For 15 cases were detected immunological characteres by FCM,13 cases showed abnormalities.(6)For 29 cases of MDS/MPNs had been analyzed chromosome karyotypes and 12 out of them (41.4％) were abnormal,Ph chromosomes and those AML-defining translocations were all negative,+ 8 and 7-involved- karyotypes were more frequent.(7)23 cases were detected molecular genetic features,in which were all negative.BCR/ABL1 and JAK2 V617F mutation were all negative in the 13 cases of aCML.JAK2 V617F mutation was positive in 1 case of MDS/MPN-U.ConclusionsMost MDS/MPNs had paleness and fatigue,light to mild anemia,cytosis,monocytes low grade of blast and immature neutrophils in peripheral blood with dysplasia in bone marrow.JMML seems has more severe clinical features and more distinguishing laboratory characters.Immunological abnormalities and abnormalkaryotypes are found frequently in MDS/MPNs with no statistical differences among the four subtypes.There is no specific molecular abnormals in MDS/MPNs.( Chin J Lab Med,2012,35:832-837)