Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

Objective:To explore the real work experience and needs of nursing assistants of elderly patients with disability and mental disorders, and provide reference for relevant institutions to develop a reasonable support system and promote their physical and mental health.Methods:From October to November 2022, purposive sampling was used to select nursing assistants of elderly patients with disability and mental disorders from the Affiliated Brain Hospital of Guangzhou Medical University as the research subject. The phenomenological method was used to conduct in-depth interviews, recordings, and transcripts of 12 nursing assistants. The Colaizzi analysis program was used to analyze, organize, refine, and summarize.Results:A total of five themes were extracted, including multiple emotional experiences, lack of rest and relaxation, insufficient professional identity and external support, lack of care knowledge and skills, heavy workload and poor treatment.Conclusions:Accompanying management institutions and hospitals need to strengthen their attention to nursing assistants, reduce their physical and mental burden, attach importance to skill training, increase welfare benefits, enhance professional identity, and improve the quality of care.

Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.

Objective:To investigate cognitive function changes and their influential factors in patients with ischemic stroke and leukoaraiosis.Methods:A total of 500 patients with ischemic stroke who received treatment in Yiwu Central Hospital from January 2018 to October 2019 were included in this study. They were divided into simple ischemic stroke group ( n = 200) and ischemic stroke complicated by leukoaraiosis group (combination group, n = 300). The infarct location and the degree of leukoaraiosis in the combination group were analyzed. An additional 150 volunteers who concurrently underwent the Cognitive Function Test in the same hospital were selected as controls. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Patients in the combination group were divided into cognitive impairment group (MoCA score ≥ 26 points) and non-cognitive impairment group (MoCA score < 26 points) according to MoCA score. The risk factors of cognitive impairment in patients with ischemic stroke and leukoaraiosis were analyzed. Results:The scores of the MMSE, MoCA, Clock Drawing Test (CDT), Verbal Fluency Test (VFT), and Digit Span Test (DST) in the control group were (28.93 ± 2.70) points, (28.35 ± 2.74) points, (4.69 ± 1.14) points, (4.94 ± 0.42) points, and (14.33 ± 1.66) points respectively. They were (26.92 ± 2.18) points, (25.02 ± 3.52) points, (3.61 ± 1.60) points, (4.77 ± 0.46) points, and (11.73 ± 1.16) points, respectively in the simple ischemic stroke group and (24.91 ± 2.79) points, (20.70 ± 3.06) points, (2.87 ± 1.23) points, (4.07 ± 0.85) points, and (10.82 ± 0.93) points respectively in the combination group. There were significant differences in the scores of the MMSE, MoCA, CDT, VFT, and DST among the three groups ( F = 124.50, 318.50, 93.43, 112.60, 428.60, all P < 0.001). Significant differences in the scores of the MMSE, MoCA, CDT, VFT, and DST were observed between patients with different degrees of leukoaraiosis ( F = 69.09, 102.40, 20.98, 60.90, 57.00, all P < 0.001). Spearman correlation analysis results showed that the scores of the MMSE, MoCA, CDT, VFT, and DST were negatively correlated with the degree of leukoaraiosis ( r = -0.61, -0.69, -0.43, -0.56, -0.44, all P < 0.05). Logistic regression analysis results showed that age, history of smoking and drinking, history of diabetes, history of stroke, and infarct location were the independent risk factors for cognitive impairment in patients with ischemic stroke and leukoaraiosis. Education level was a protective factor against ischemic stroke and leukoaraiosis. Conclusion:The degree of cognitive impairment in patients with ischemic stroke and leukoaraiosis is related to the degree of leukoaraiosis. Age, history of smoking and drinking, history of diabetes, history of stroke, infarction location, and education level are the influential factors of cognitive impairment.

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.

Objectives:To investigate the value of histopathological growth patterns (HGP) in predicting the 3-year progression free survival (PFS) after resection the liver metastasis from patients with colorectal cancer.Methods:The clinicopathological data of the 111 patients with liver metastasis of colorectal cancer diagnosed at Peking University People′s Hospital, Beijing, China from January 2007 to January 2017 were analyzed. After excluding the patients who did not meet the inclusion criteria, a total of 80 patients were analyzed. According to the international expert consensus on HGP, the HGP types of liver metastasis were evaluated. The correlation between HGP and other clinicopathological factors was analyzed using χ 2 or Fisher test. Kaplan-Meier survival curve was used to examine 3-year PFS in the patients with liver metastasis of colorectal cancer by HGP. The independent risk factors of 3-year post-resection PFS were determined using univariable and multivariable analyses. Results:A total of 80 cases were analyzed, including 43 cases of desmoplastic type (54%), 32 cases of replacement type (40%), 3 cases of pushing type (4%), and 2 cases of mixed type (2%). There was no correlation of HGP with age, gender, time of metastasis, tumor burden, histological grade, mucous differentiation or microsatellite instability. The 3-year post-resection PFS of the patients with desmoplastic type was significantly longer than that of patients with replacement type. The univariable and multivariable analyses showed that HGP was an independent prognostic factor.Conclusions:The HGP of colorectal cancer metastases to the liver mainly present as desmoplastic and replacement types. HGP is an independent prognostic factor for the patients with liver metastasis of colorectal cancer after resection of the metastasis. Therefore, HGP should be clearly indicated in the pathological report to help guide clinical treatments.

Objective:To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC).Methods:Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G 1, G 2 or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G 2 EC group, G 1 EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results:(1) Totally 57 eligible patients were included in this study, including 11 cases with G 2 EC, 22 cases with G 1 EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G 2 EC, G 1 EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G 2 EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G 2 EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference ( P>0.05). However, time interval to pregnancy was shorter in G 2 EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions:Fertility-preserving treatment for patients with stageⅠa, G 2 endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P<0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P>0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups (P<0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively (P<0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P<0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months (P<0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.

Objective To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SETⅡ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SETⅠand 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P<0.05). There was no significant difference among the above indexes between HGSC-SETⅠand HGSC-SETⅡ(P>0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups (P<0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively (P<0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SETⅠ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P＜0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months (P＜0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.

Objective To investigate the value of ultrasound screening for congenital cytomegalovirus (CMV) infection in fetuses and to summarize the clinical manifestations.Methods From January 2012 to December 2017,we retrospectively analyzed the clinical data of 905 gravidas who received invasive prenatal diagnosis in Fujian Provincial Maternity and Children's Hospital for abnormal prenatal ultrasound findings including ventriculomegaly,intracranial calcification,microcephaly,echogenic bowel and fetal growth restriction (FGR).CMV DNA loads in amniotic fluid and neonatal urine were detected by real-time polymerase chain reaction.CMV-specific IgM and IgG in umbilical cord and neonatal peripheral blood were detected by commercial enzyme 1 inked immunosorbent assay kits.Eighteen fetuses with normal karyotype were diagnosed as congenital CMV infection.Relationships of ultrasound features and CMV DNA loads in amniotic fluid to pregnancy outcomes were analyzed with x2 test or Fisher's exact test.Results (1) Congenital CMV infection was detected in 18 fetuses in this study with an detection rate of 1.99％ (18/905).Three pregnancies were terminated immediately after the diagnosis was confirmed,two terminated when the ventriculomegaly progressed,five terminated for hydrocephaly and eight continued to delivery.(2) Congenital CMV infection rate was significantly higher in those with two or more ultrasound abnormalities than that in those with only one abnormal indicator [3.92％(8/204) vs 1.28％(9/701),x2=4.619,P=0.032].Fetuses with craniocerebral abnormalities were more likely to have congenital CMV infection than those without [3.11％(13/418) vs 0.82％(4/487),x2=6.392,P=0.012].(3) Among the 18 fetuses with congenital CMV infection,those with serious ultrasound abnormalities had a significantly higher rate of adverse outcomes than those without (11/11 vs 3/7,Fisher's exact test,bilateral P=0.043).No significant difference in the rate of adverse outcomes was found between fetuses with low and high CMV DNA loads in amniotic fluid (3/4 vs 12/14,Fisher's exact test,bilateral P=1.000).Conclusions Ultrasound abnormalities including ventriculomegaly,intracranial calcification,microcephaly,echogenic bowel and FGR,especially those with multiple abnormalities and brain abnormalities,increased risk of congenital CMV infection.Congenital CMV fetuses with serious ultrasound abnormalities has adverse outcomes.