Table of Content

05 May 2023, Volume 43 Issue 5

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Original Articles

Changes and significance of leukotriene C4 and type 2 innate lymphoid cell in bronchopulmonary dysplasia

JI Wei, ZHU Yue, YAO Huici, LU Hongyan

2023, 43(5):  711-716.  doi:10.16352/j.issn.1001-6325.2023.05.0711

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Objective To investigate the dynamic changes of leukotriene C4 (LTC4), type 2 innate lymphoid cell(ILC2) and related cytokines (IL-4, IL-5 and IL-13) in the lung tissue of mice with bronchopulmonary dysplasia (BPD). Methods C57BL / 6 mice were randomly divided into air group and hyperoxia group.The hyperoxia group was exposed to 85% oxygen for 1, 7 and 14 days to replicate the BPD model.HE staining microscopy was used to observe the pathological changes of the lung tissue of mice. The percentages of ILC2 and CysLT1R⁺ILC2 were detected by flow cytometry.The contents of LTC4, IL-4, IL-5 and IL-13 were detected by ELISA.Western blot was used to detect the expression of LTC4-C synthase (LTC4S).RT-qPCR was used to detect the mRNA expression of LTC4S and cysteine leukotriene type 1 receptor (CysLT1R). Results Compared with air group, the percentage of ILC2 and CysLT1R⁺ILC2 in hyperoxia group and the expression of CysLT1R mRNA all increased(P＜0.05);The expression of IL-4, IL-5 and IL-13 in the hyperoxia group increased and were higher than those in the air group at the same time point (P＜0.05);LTC4 content, LTC4S protein and mRNA expression were significantly increased in hyperoxia group (P＜0.05). Conclusions In BPD, LTC4 increases and may induce the increase of ILC2 and related cytokines (IL-4, IL-5 and IL-13) through CysLT1R.

Gene Cdca2 knockout has no significant effect on spermatogenesis and fertility in mice

LIU Jun, ZOU Dingfeng, Miao Shiying, SONG Wei, LI Kai

2023, 43(5):  717-723.  doi:10.16352/j.issn.1001-6325.2023.05.0717

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Objective To explore the physiological function of gene for cell devision cycle associated 2 (Cdca2), a highly expressed testis gene, in spermatogenesis and fertility in mice. Methods The expression of Cdca2 in different tissues of mice was detected by Q-PCR and Western blot; Using CRISPR/Cas9 gene editing technology and Cre-loxP mediated recombination system, a mouse strain with Cdca2 tissue specific knockout was constructed; By hematoxylin-eosin(HE) staining and morphological analysis, the effect of CDCA2 deletion on spermatogenic cell morphology at different stages of spermatogenesis was studied; The effects of CDCA2 deletion on sperm motility and motility parameters were detected by an automatic sperm detection and analysis system; The effect of CDCA2 deletion on the fertility of male mice was examined by fertility test. Results Cdca2 was a highly expressed gene in testis; Cdca2 germ cell specific knockout mice were successfully obtained by CRISPR/Cas9 technology and reproductive system; CDCA2 deletion in mice had no statistically significant effect on spermatogenic cells, sperm motility parameters and male fertility at all stages of spermatogenesis. Conclusions Cdca2 is probably not necessary for spermatogenesis and male fertility maintenance in mice.

Exploring the potential application of liver organoids of mouse as developmental models upon Hnf4α knockout

ZHANG Zhiyu, CAO Jun, LIANG Junbo

2023, 43(5):  724-732.  doi:10.16352/j.issn.1001-6325.2023.05.0724

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Objective To explore the potential application of the intrahepatic cholangiocyte organoid (ICO) differentiation model to study liver development. Methods Combining CRISPR/Cas9 gene editing technology and ICO differentiation model, bulk RNA-seq data of the organoids cultured in expansion medium, differentiation medium, and differentiation medium after Hnf4α knockout were used to analyze the transdifferentiation process of ICO, and public single-cell transcriptome data sets were used to analyze the differentiation during fetal liver development. The two differentiation processes were compared in three aspects: the change of gene expression, biological function, and transcriptional regulation taking Hnf4α regulon as an example. Results The change of gene expression during ICO transdifferentiation was almost consistent with that in liver development. The up-regulated genes during transdifferentiation were mainly enriched in metabolism-related pathways closely associated biological functions of liver parenchymal cells. The downstream target genes of Hnf4α during ICO transdifferentiation were overlapped with those in fetal liver development. Conclusions ICO transdifferentiation model can partially simulate the differentiation process of fetal liver development.

Correlation between different FGFR1 mutations and congenital hypogonadotropic hypogonadism

YANG Yufan, WANG Xi, NIE Min, WU Xueyan, MAO Jiangfeng

2023, 43(5):  733-738.  doi:10.16352/j.issn.1001-6325.2023.05.0733

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Objective To investigate whether multiple gene mutations were existed to cause congenital hypogonadotropic hypogonadism(CHH), by screening genes in CHH patients with FGFR1 mutations. Methods FGFR1 mutations were identified in 15 CHH patients. Other CHH-related genes were screened in these patients. Bioinformatics software was used to analyze the pathogenicity of gene variant. Results 1)Mutations in FGFR1 were inherited from parents in 9 patients (inherited mutation group)in spite of the fact, their parents showed normal reproductive axis function. 2)In the inherited mutation group, 6 patients harbored another mutation including PROKR2(W178S), FGF8(T121N), HS6ST1(P242L), SEMA3A(R734W), LZTR1(Q10Rfs*15) and FGFR1 compound heterozygous mutation. Multiple gene mutations may lead to CHH. 3)Six patients were found to have de novo mutations in FGFR1(de novo mutation group) but not no other pathogenic CHH related gene mutations. Conclusions FGFR1 mutations inherited from parents may require another blow from CHH-related genes to cause CHH. This study expands our understanding of the pathogenesis of CHH caused by digenic mutation.

RNA binding profile analysis of N-acetyltransferase 10 in K562 cells

LI Gaoyuan, WANG Yanran, WANG Fang, YU Jia

2023, 43(5):  739-744.  doi:10.16352/j.issn.1001-6325.2023.05.0739

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Objective To delineate RNA binding profile of NAT10(N-acetyltransferase 10) in human chronic myelogenous leukemia cell line K562. Methods Enhanced UV crosslinking and immunoprecipitation (eCLIP) were used to capture the transcript collection bound by NAT10 in K562 cells. Data were obtained through high throughput sequencing and then analyzed with bioinformatics. The type and regions of NAT10 binding genes were identified via peak-calling and annotation. The function of the binding RNA was further explored by gene function enrichment analysis. Results NAT10 binding transcripts which were enriched in 3′UTR region, were mainly protein coding genes. Further analysis showed that they were functionally associated with DNA damage and repair. Conclusions NAT10 may regulate gene expression by binding to the 3′UTR region of mRNA associated with DNA damage repair.

Redox modification of CLOCK mediates the regulatory function of endogenous H₂O₂ in mouse cellular respiration

CHANG Weiwei, LI Xunkai, ZHANG Zhuqin, CHEN Houzao, LIU Depei

2023, 43(5):  745-750.  doi:10.16352/j.issn.1001-6325.2023.05.0745

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Objective To explore the mechanisms of transcription factor circadian locomalor output cycles kaput(CLOCK) in mediating regulatory function of endogenous hydrogen peroxide(H₂O₂) for cell respiration. Methods Cellular oxygen consumption capacity and glycolysis in Clock^C195S mouse embryonic fibroblasts (MEFs) and adult fibroblasts(MAFs) were tested by Agilent Seahorse XF Cell Mito Stress Test Kit and Glycolysis Stress Test Kit. The expression of key genes participating in cell respiration was detected by q-PCR. The endogenous H₂O₂ levels and the redox modification of CLOCK were detected by Amplex^® Red Hydrogen Peroxide/Peroxidase Assay Kit and biotin-conjugated iodoacetamide (BIAM) were used respectively after the treatment of antioxidant Trolox. Changes in the oxygen consumption capacity and in key respiratory gene expression after the treatment of antioxidant Trolox were also tested in Clock^wt and Clock^C195S MEFs. Results Cellular oxygen consumption capacity, glycolysis and the expression of NMNAT2, a key enzyme in nicotinamide adenine denudeotide(NAD) biosynthesis, as well as NAD content all decreased in Clock^C195S MEFs. The treatment with Trolox decreased endogenous H₂O₂ level and dampened respiration capacity in Clock^wt MEFs but not in Clock^C195S MEFs. Conclusions CLOCK mediates the regulation of endogenous H₂O₂ for cellular respiration through its redox modification at Cys195.

Influence of PABPC1 on translation activity in human monocytic leukemia cell line THP-1

ZHAI Xueying, WANG Fang, YU Jia

2023, 43(5):  751-754.  doi:10.16352/j.issn.1001-6325.2023.05.0751

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Objective To investigate the effect of cytoplasmic poly(A) binding protein-1(PABPC1) on translation of human monocytic leukemia cells line THP-1. Methods Specific short hairpin RNA(shRNA) was transfected into THP-1 cells. Western blot was used to verify the interference efficiency. The polysome profiling was used to examine the translation ability of THP-1 cells. Results The expression of PABPC1 protein was decreased in shPABPC1 transfected THP-1(P＜0.05). Compared with control group, the translation ability of THP-1 cells in shPABPC1 group was reduced. Conclusions Knockdown of PABPC1 may inhibit the translation in THP-1 cells and PABPC1 is a potential target for the treatment of acute myeloid leukemia (AML).

Effect of obeticholic acid on glucolipid homeostasis in high-fat fed C57BL/6J mice

WANG Xing, GUO Nan

2023, 43(5):  755-761.  doi:10.16352/j.issn.1001-6325.2023.05.0755

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Objective To investigate the effects of obeticholic acid (OCA) on glucolipid metabolism in high-fat fed C57BL/6J mice. Methods After 12 weeks of high-fat diet (HFD) feeding, C57BL/6J mice were randomly divided into two groups: model group (model) and OCA intervention group (10 mg/kg, gavage for six weeks), with 10 in each. The C57BL/6J mice were fed with normal diet for 12 weeks as the control group. The model group and the control group were given 0.5% sodium carboxymethyl cellulose (CMC-Na) by gavage. During the experiment, oral glucose and insulin tolerance tests were conducted. At the end of the experiment, the liver function related indicators were measured in serum, and the liver weight was recorded. The lipid-related indicators were measured in liver, and HE staining microscopy was performed. RT-qPCR was used to detected the expression of genes related to lipid metabolism in liver. Results After glucose loading and insulin injection, the blood glucose at each time point and area under curve (AUC) of the model group were significantly higher than those of the control group (P＜0.01). Abnormal glucose tolerance in OCA intervention group was reversed(P＜0.05) and the insulin sensitivity of the model group mice was improved(P＜0.05). The serum level of triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low density lipoprotein total cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the model group was all significantly higher than those in the control group (P＜0.01), and HDL-C level was evidently lower than that in the control group (P＜0.01). The OCA intervention group could significantly reduce the serum levels of TG, TC, FFA, LDL-C, ALT, AST (P＜0.01) and increase the serum HDL-C content in the model group (P＜0.01). The contents of TG, TC, and FFA in the liver of the model group were significantly higher than those in the control group (P＜0.01), and OCA intervention group did alleviate the hepatic steatosis in the model group (P＜0.05). Compared with the control group, the expression of FXR/SREBP pathway related genes in model group was abnormal (P＜0.01), and OCA intervention reversed abnormal expression of FXR/SREBP pathway related genes in model group (P＜0.05). Conclusions OCA may improve the lipid metabolism disorder in the liver of HFD mice by regulating the FXR/SREBP pathway, thus improve the impaired glucose tolerance and insulin resistance in HFD mice.

Apolipoprotein E negatively regulates Golgi membrane protein 73 to inhibit the proliferation of mouse liver cancer cell lines

HOU Mengjie, ZHAO Na, HUANG Fuqiang, WANG Yanan, LIU Fangming

2023, 43(5):  762-770.  doi:10.16352/j.issn.1001-6325.2023.05.0762

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Objective To explore the potential regulatory relationship between apolipoprotein E (APOE) and Golgi membrane protein 73 (GP73) for elucidating its significance in the proliferation of liver cancer cells. Methods Online databases were checked for correlation between APOE and GP73 expression in liver cancer. Mice were divided into control and Apoe knockout groups, control and Gp73 knockout groups. Cell lines were divided into Gp73 knockdown group, Apoe knockdown group (transfected with small interference RNA or infected with lentivirus) and corresponding control, GP73 over-expression group, APOE over-expression group (transfected with over-expression plasmids) and corresponding control, GP73 low expression group (transfected with small interference RNA or treated with rapamycin) and control group. Western blot was used to detect APOE and GP73 protein expression, and CCK8 assay was used to detect cell proliferation. Results GP73 was negatively correlated with APOE in liver cancer (P＜0.001).GP73 deficiency did not alter APOE expression, while APOE deficiency enhanced GP73 expression in mice(P＜0.001). Consistently, GP73 did not affect APOE expression but APOE negatively regulated GP73 expression in liver cancer cells (P＜0.01). Besides, Apoe knockdown promoted mouse liver cancer cell proliferation(P＜0.01), which was reversed by GP73 inhibition (P＜0.001). Conclusions APOE suppresses GP73 expression. Inhibition of GP73 may reverse APOE knockdown-accelerated cell proliferation. Therefore, APOE inhibits cell proliferation through suppression of GP73 which may contribute to liver cancer progression and be targeted for the treatment of hepatic cancer.

Protective effect of BM-MSCs-derived exosome-mediated ferroptosis against anoxia-reoxygenation injury in rat cardiomyoblastl cell line H9c2

YAN Lin, LU Juexiu, LUO Ying, LIU Xianxia

2023, 43(5):  771-776.  doi:10.16352/j.issn.1001-6325.2023.05.0771

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Objective To investigate the protective effect and molecular mechanism of bone marrow mesenchymal stem cells(BM-MSCs)-derived exosomes against anoxia-reoxygenation (A/R) injury in rat cardiomyoblast cell line H9c2. Methods The A/R injury model of H9c2 cells was constructed. Electron microscopy and Western blot were used to identify BM-MSCs-derived exosomes(BM-MSCs-exos); PHK26 red fluorescence-labeled exosomes were used to observe the endocytosis of H9c2 cells; CCK-8 assay was used to detect cell viability; EdU cell proliferation assay was used to detect cell proliferation ability; Ferroptosis-related detection kits were used to determine Fe²⁺, MDA, GSH content; Flow cytometry was used to detect reactive oxygen species free radical ROS level. Results BM-MSCs-exos were successfully identified, and the endocytosis of BM-MSCs-exos by H9c2 cells was found. Compared with A/R group, cell viability and proliferation in A/R+ MSCs-exo group were significantly improved (P＜0.05).Ferroptosis marker protein GPX4, SLC7A11 increased; Transferrin receptor TFR1 expression decreased(P＜0.05); And Fe²⁺ ions, MDA, ROS all decreased while GSH increased(P＜0.05). After treatment with the ferroptosis inducer Erastin, the protective effect of BM-MSCs-exo against A/R injury in H9c2 cells was significantly reduced (P＜0.05). Conclusions BM-MSCs-exos can alleviate A/R-induced cardiomyocyte injury, and is potentially mediated by inhibiting cardiomyocyte ferroptosis.

Ganglioside GD2 is a potential candidate marker for lung cancer stem cells

LI Zhen, DUAN Zhaojun, LUO Yunping

2023, 43(5):  777-784.  doi:10.16352/j.issn.1001-6325.2023.05.0777

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Objective To explore the feasibility of ganglioside GD2 as a marker for lung cancer stem cells (LCSCs). Methods Cancer stem cells (CSCs) of lung cancer cell lines were enriched by spheroid culturing in vitro; The expression of stemness-related genes and GD3 synthase (GD3S) in LCSCs were detected by RT-qPCR and Western blot; The expression of GD2 and other stemness phenotypes in lung cancer cell line A549 were detected by flow cytometry; Cell proliferation was detected by CCK8 assay; Cell invasion and migration in vitro were examined by Transwell and wound healing assays; The oncogenicity of different subpopulations in cell line A549 was compared with tumor xenograft model. Results CSCs of A549 cell were successfully enriched by and the percentage of GD2⁺ cells was 0.57% in adherent cell, but the percentage of GD2⁺ cells was able to increase to 20.4% after spheroid culturing. In comparison with GD2^- A549 cells, GD2⁺ A549 cells showed significantly enhanced cell proliferation (P＜0.05),invasion (P＜0.05) and migration ability (P＜0.01) in vitro. There was a close association between GD2 and two other LCSCs phenotypes, and the expression level of GD2 was positively correlated with the expression of CD44 (P＜0.01) and EpCAM (P＜0.001). The results in vivo indicated that tumors formed by GD2⁺ A549 cells grew faster (P＜0.001) and were more malignant (P＜0.01) as compared to GD2^- A549 cells. Conclusions Ganglioside GD2 is a potential marker for LCSCs to identify cancer stem cells, providing a novel strategy of GD2-targeted lung cancer immunothearapy.

Clinical Sciences

Analysis of clinical characteristics of 25 patients with hypereosinophilia complicated with peripheral arterial occlusion

HAN Yingdong, WANG Song, HAN Xinxin, YIN Yue, WANG Yu, ZHANG Yun, ZENG Xuejun

2023, 43(5):  785-789.  doi:10.16352/j.issn.1001-6325.2023.05.0785

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Objective To improve the understanding of hypereosinophilia(HE) rarely complicated with peripheral arterial occlusion. Methods Among 555 inpatients with HE from Peking Union Medical College Hospital from April 2012 to October 2021, 25 cases complicated with peripheral artery occlusion were involved according to the inclusion and exclusion criteria. The initial clinical features, symptoms of arterial occlusion and organ involvement of the 25 patients were summarized. After age and gender matching, 34 HE patients without peripheral artery occlusion as the control group. Clinical manifestations, treatment and prognosis of the two groups were compared. Results All patients were male, with an average of (44.5±16.2) years old. The main involved arteries included ulnar artery, radial artery, tibial artery and peroneal artery. The IgA level and involvement of skin and peripheral nerves in the case group were significantly higher than that in control group(P＜0.05). 76% and 80% of the patients in the case group received anticoagulant therapy or antiplatelet therapy, respectively, 20% received steroid pulse therapy and 64% received immunosuppressive therapy, above which were significantly higher than that in control group(P＜0.05). As indicated by eosinophil level, 68% and 48% of patients in the two groups achieved complete remission, respectively. Conclusions The skin and peripheral nervous system are the most commonly involved organs in HE patients complicated with peripheral arterial occlusion, and administration of steroids and immunosuppressive medicines may lead to good prognosis.

Effect of compound α-ketoacid on quality of life and self-perceived burden in diabetic patients undergoing peritoneal dialysis

YIN Yue, WANG Liyan, HUANG Hongdong

2023, 43(5):  790-793.  doi:10.16352/j.issn.1001-6325.2023.05.0790

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Objective To compare effects of compound α-ketoacids on quality of life(QOL) and self-perceived burden(SPB) of diabetes patients undergoing peritoneal dialysis. Methods Totally 86 diabetes patients received continuous ambulatory peritoneal dialysis(CAPD) for more than 3 months in Friendship Hospital were divided into observation group (n=44) and treatment group (n=42). After 6 months of treatment, the quality of life of both groups was assessed with the World Health Organization Quality of Life Scale-brief Form Questionnaire(WHOQOL-BREF) and the self-perceived burden was assessed with the Self-perceived Burden Scale (SPBS). Results After 6 months, the glycosylated hemoglobin in the treatment group was 5.72%±1.03%, which was significantly lower than 6.70%±1.17% found in observation group. The physiological field, environmental field and total score of treatment group was significantly higher than those in observation group(P＜0.05), and there was no difference was found self-perceived burden. Conclusions Simultaneous administration of peritoneal dialysis plus compound α-ketoacids supplement may significantly improve the quality of life of diabetes patients.

Impact of SARS-CoV-2 vaccination on pregnancy outcome

ZHANG Wei, YU Yixiang, WANG Lin, WEN Ming

2023, 43(5):  794-797.  doi:10.16352/j.issn.1001-6325.2023.05.0794

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Objective To explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on pregnancy outcome in women of childbearing age. Methods The project was a multi-center investigation covering May 2021 to November 2022 the First People's Hospital of Wuhu, Wuwei City People's Hospital, Nanling Hospital, Wuhu Fanchang District People's Hospital childbirth and abortion. The investigation included 1 987 cases of pregnant and parturient women of childbearing age, with 1 346 cases of SARS-CoV-2 vaccinated, and 641 unvaccinated. Pregnancy outcomes including neonatal weight, 5-minute Apgar score, and neonatal intensive care unit (NICU). Results There were differences between the vaccinated group and the unvaccinated group in age distribution of pregnancy and whether the women were multiparous(P＜0.05,P＜0.001). There was no difference in the fetal live birth rate between the two groups. Excluding pregnancy outcomes abortion and stillbirth, the results showed that there was no differencein delivery outcomes (including neonatal morphology, body weight, NICU and 5-minute Apgar score between the two groups. Conclusions SARS-CoV-2 accination has no negative impact on pregnancy outcome in childbearing women.

Prevalence investigation of depression and associated risk factors in the elderly with hypertension in Yuetan community of Beijing

WANG Chunyuan, BIAN Lili, LI Xiaoxiao

2023, 43(5):  798-803.  doi:10.16352/j.issn.1001-6325.2023.05.0798

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Objective To investigate the prevalence and risk factors of depression in elderly with hypertension in a community of Beijing, so as to provide evidence for individualized treatment of healthy aging. Methods Six hundred and thirteen elderly patients aged over 60 with hypertension were selected from Yuetan community of Beijing by overall sampling method from June 2019 to October 2019. Patient Health Questionnaire (PHQ-9) scale was used to determine depression. General demographic information, chronic diseases and health status of the subjects were collected at the same time. Single factor and binary logistic regression models were used to analyze the associated factors and independent risk factors of depression in elderly hypertensive patients of different genders. Results The overall incidence rate of depression in elderly hypertensive patients in the community was 11.58%, among which male accounted for 9.81% while female 12.53%. Univariate analysis showed that the incidence of depression in male elderly with hypertension was associated with sulfuring form coronary heart disease and sleep disorders, while in female associated with suffering from economic pressure, hearing impairment, vision impairment, chronic gastritis, chronic hepatobiliary diseases and sleep disorders, with a statistically significant difference (P＜0.05). Multivariate binary logistic regression analysis showed that male elderly with hypertension suffering from sleep disorders had a higher risk of depression, with an OR value of 4.825 (95% CI: 1.777-13.105), while female elderly sulfuring from economic pressure, hearing impairment, visual impairment, chronic gastritis and sleep disorders had a higher risk of depression, with OR values of 14.362 (95% CI: 2.224-92.747), 11.174 (95% CI: 2.535-49.258), 3.994 (95% CI: 1.444-11.043), 3.780 (95% CI: 1.608-8.887), 4.968 (95% CI: 2.430-10.156), respectively. Conclusions The prevalence of depression is high among the elderly with hypertension in Yuetan community of Beijing. The majority of elderly with hypertension showed mild degree depression. The incidence rates of elderly between genders are similar. Sleep disorder is an independent risk factor and economic stress, visual impairment, hearing impairment,chronic gastritis and sleep disorder as indepandent risk factors are more significant in old females with hypertension.

Assessment for preliminary results of ‘PUMCH model’ for urolithiasis metabolic evaluation

QIAO Yi, XIAO He, LUO Hanqing, FAN Xiaohong, WANG Ou, LI Rongrong, YU Yang, JI Zhigang, LI Hanzhong

2023, 43(5):  804-808.  doi:10.16352/j.issn.1001-6325.2023.05.0804

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Objective To review the experience of metabolic evaluation of urinary stones in Peking Union Medical College Hospital, and summarize the ‘PUMCH model’ of metabolic evaluation. Methods With descriptive evaluation method, this study reviewed and analyzed 534 metabolic evaluation cases in the urology department of Peking Union Medical College Hospital from Jan. 2016 to Dec. 2021. The distribution differences of stone patients in gender, medical history, stone shape, stone composition, renal function, systemic metabolism and 24-hour urine metabolism were observed. Results This study found that males were more than females in terms of gender differences in stone patients; The average course of stone disease was about 10 years, and the first symptom was mainly renal colic; Calcium oxalate was the most common stone component; Kidney stone was more than urethral stone; Hyperlipidemia was the most common in patients with stones; The low concentration of urinary citrate was the most significant. Conclusions As a new method of stone diagnosis and treatment, the ‘PUMCH model’ of metabolic evaluation can comprehensively evaluate the patients' stone incidence and systemic metabolic abnormalities, which has a strong guiding role in stone treatment and prevention.

Technology and Methodology

Comparative investigation for auto-fluorescence sample detection by evaluating conventional and spectral flow cytometers performance

CHEN Jiahuan, LI Dandan, SUN Yan, WANG Yilei, WANG Duo, KONG Jie, LIU Xiaoling

2023, 43(5):  809-816.  doi:10.16352/j.issn.1001-6325.2023.05.0809

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Objective To compare the performance of conventional and spectral flow cytometers in detecting auto-fluorescence samples. Methods Single cell samples with auto-fluorescence were prepared and stained by annexin V(AV)binding and propidium iodure (PI) to detect apoptosis. The same auto-fluorescence sample was run on conventional and spectral flow cytometers side by side. Results By avoid using FITC in conventional cytometers, the better result was gotten in detecting auto-fluorescence samples. Full spectrum cytometry presented better resolution even there was spectral overlap. It was easy to discriminate the signals derived from auto-fluorescence and FITC. The protocol of annexinV binding and PI staining to analyze apoptosis was optimized. Conclusions Spectral flow cytometry shows relatively excellent performance under certain conditions in detecting of apoptosis derived from auto-fluorescence samples.

Mini Reviews

Progress on the role of histidine phosphatase in the occurrence of some diseases

GUO Ge, LIU Chunlei

2023, 43(5):  817-821.  doi:10.16352/j.issn.1001-6325.2023.05.0817

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Protein phosphorylation is involved in the regulation of a variety of biological processes. Histidine phosphatase dephosphorylates proteins containing histidine phosphorylation. Therefore, histidine phosphatase dysfunction can lead to the occurrence of a variety of clinical diseases, such as tumors, metabolic diseases, etc. This review summarizes the composition of histidine phosphatase, the relationship between histidine phosphatase and clinical diseases in orer to provide a new pathway for the clinical treatment of diseases.

Research progress of orexin on the regulation of cardiovascular activities

ZHU Minxia

2023, 43(5):  822-826.  doi:10.16352/j.issn.1001-6325.2023.05.0822

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Orexin(OX) is a neuropeptide mainly released by the hypothalamus. In the central nervous system, orexin neurons form extensive connections with other neuronal nuclei and participate in energy metabolism, sleep cycle and cardiovascular activity regulation. Orexin plays an important role in the maintenance of normal blood pressure. The high expression of orexin and their receptors is involved in the development of spontaneous hypertension, stress hypertension and other types of hypertension.

Research progress on regulatory mechanisms of circular RNA nuclear receptor interacting protein 1 in tumor occurrence and development

GAO Xin, YU Yongbo, WANG Haicun, JIANG Xingming, WANG Zhidong

2023, 43(5):  827-832.  doi:10.16352/j.issn.1001-6325.2023.05.0827

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Circular RNA (circRNA) is a class of single-stranded covalently closed non-coding RNA molecules widely expressed in eukaryotic cells. Recent studies have found that circRNA has been involved in modulating biological processes such as cell proliferation, differentiation, and apoptosis so it is the key regulator of tumor occurrence and development. Circular RNA nuclear receptor interacting protein 1(circ_NRIP1), as a circular RNA, is abnormally expressed in various human cancers and potentially regulates malignant biological behaviors such as tumor proliferation, invasion and migration. Elucidating the regulatory mechanisms of circ_NRIP1 in tumor occurrence and development may provide a new strategy for tumor diagnosis and treatment.

Research progress of anti-apoptotic inhibitor venetoclax in treatment of myeloid leukemia

XIANG Caixia, HUANG Bintao, HAO Jian

2023, 43(5):  833-836.  doi:10.16352/j.issn.1001-6325.2023.05.0833

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The anti-apoptotic protein Bcl-2 inhibitor venetoclax (Ven) can significantly improve the remission rate and long-term survival of elderly and relapsed/refractory acute myeloid leukemia(AML) patients who are not sensitive to intensive chemotherapy. TP53/FLT3 mutation, abnormal energy metabolism of fatty acids and amino acids, high expression of Mcl-1 protein and activation of ferroptosis program occur during clinical treatment are all involved in the development of Ven resistance and leukemia progression. Further exploration of the mechanisms leading to Ven resistance in myeloid leukemia may help to inhibit the development of Ven resistance and continuously improve the long-term survival of leukemia patients.

Progress on the role of 11β-HSD1 in inflammation,development of hepatocellular carcinoma and immunity

LEI Xingyu, FENG Xuesong, CHAO Xu

2023, 43(5):  837-841.  doi:10.16352/j.issn.1001-6325.2023.05.0837

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The 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) with anti-inflammatory or pro-inflammatory effects in inflammatory diseases is related to metabolism, as well as in the immune response through regulatpn of glucocorticoid (GC) synthesis. The expression and functional activity of 11β-HSD1 are potentially induced by pro-inflammatory cytokines, this process relies on the NF-κB signaling pathway and is ultimately determined by the utilization levels of HSD11B1 P1 and P2 promoters. In addition, 11β-HSD1 inhibits the proliferation of hepatocellular carcinoma by reducing glucose intake and glycolysis in hepatocellular carcinoma, and thus plays a role in the development of T cells in thymus and the form of angiogenesis by regulating the level of GC. Understanding the molecular regulatory mechanism of 11β-HSD1 in inflammatory diseases, carcinogenesis, development and immune response is conducive to exploring the occurrence and development of related diseases.

Research advance on the best mechanical ventilation mode of laryngeal mask airway for general anesthesia

LIN Yuqi, YI Jie

2023, 43(5):  842-847.  doi:10.16352/j.issn.1001-6325.2023.05.0842

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As an important supraglottic airway tool,laryngeal mask airway(LMA) has been used more and more widely in clinic. In addition to being used in gynaecological and pediatric small-scale elective surgery, it has also been used in elderly patients' surgery, obese patients' auxiliary ventilation, thoracic surgery, and even emergency airway management. There are different ventilation modes of anesthesia machine during general anesthesia operation, but there is no conclusion on which mode to choose when using LMA. For different patients, different operations and different types of LMA, anesthesiologists can choose a relatively suitable ventilator mode and adjust respiratory parameters to reduce lung injury during mechanical ventilation, so that patients can obtain the best prognosis.

Research progress of endoplasmic reticulum stress of hypoxic pulmonary hypertension

LIU Xingxing, WANG Weiwei, YUAN Haoxin

2023, 43(5):  848-851.  doi:10.16352/j.issn.1001-6325.2023.05.0848

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Hypoxic pulmonary hypertension (HPH) is a serious complication caused by long-term hypoxia,which is characterized by persistent vasoconstriction and irreversible vascular remodeling. The hypoxia may destroy protein folding process in endoplasmic reticulum and activate endoplasmic reticulum stress(ERS). As the core response of cell stress, ERS is closely related to the development of HPH.

Research progress of NT5C2 in disease and treatment

SHU Ling, HUO Bennian, SONG Lin

2023, 43(5):  852-856.  doi:10.16352/j.issn.1001-6325.2023.05.0852

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Cytosolic 5'-nucleotidase Ⅱ(cN-Ⅱ), the protein encoded by NT5C2, can catalyze the dephosphory-lation of nucleoside monophosphate and is mainly involved in the regulation of purine nucleotide pool in cells. High expression of cN-Ⅱ mRNA is associated with poor prognosis of patients with acute leukemia (AL). Acquired NT5C2 mutation will hinder the formation of DNA and thioguanine nucleotide (TGN) conjugate, resulting in 6-mercaptpurine(6-MP) resistance. In addition, NT5C2 is a risk factor associated with type Ⅱ diabetes, schizophrenia and other diseases.

Medical Education

Problems and countermeasures in the standardized training of residents for master professional degree in clinical medicine

NIU Jianmin, ZHU Bin

2023, 43(5):  857-860.  doi:10.16352/j.issn.1001-6325.2023.05.0857

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The training of graduates for clinical medicine master degree is organized by standardized training for residents during their program. The training focuses to post competencies, capacity building of clinical diagnosis and treatment. At the same time, clinical medicine graduates should also have certain scientific research capacity. This puts forward higher requirements for the training of medical graduates. However, there are still some problems in the process of resident training for medical graduates including the contradiction between research training and clinical training,etc. This paper analyzes the problems in resident training for medical graduates and discusses the corresponding countermeasures to further improve the quality of resident training for graduates of clinical medicine.

Investigation on improvement effect of psychological intervention on students' mental health status of eight-year medical doctor program

YANG Jing, LI Mingxia, JIANG Yinan, XU Lingling, LIU Tao, ZHANG Xiaotong

2023, 43(5):  861-866.  doi:10.16352/j.issn.1001-6325.2023.05.0861

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Objective To investigate the mental health status of eight-year medical doctor program students in Peking Union Medical College and try to put forward feasible psychological support countermeasures. Methods Undergraduates of eight-year program from grades 3 to 8 in Peking Union Medical College were investigated by WeChat and questionnaires(www.wjx.cn). The differences among groups were analyzed by gender and grade. The practice group received strengthened psychological support intervention and compared with the theoretical study group. Results Totally 248 qualified questionnaires were collected and 82(33.1%) and 16(6.5%) students were rated “moderate” and “poor” in psychological self-assessment. The Life Satisfaction with Life Scores (SWLS) from 6th and 7th grade students was significantly lower than that from 3rd, 5th, and 8th grade. For other scales including depression, anxiety, and difficulties in emotional regulation scale, a tendency showed that these undergraduates from two grades had higher scores but the result was not statistically significant. Conclusions The undergraduates of eight-year doctor program still have some mental health problems especially during internship period when facing to greater pressure. Implementation of intervention may support their emotional regulation.