【Objective】 To evaluate the effect of Arntl on T cell development and T cell-mediated anti-viral immunity. 【Methods】 Arntl^F/FCD4cre⁺(KO) in mice was constructed to delete Arntl gene specifically in T cells. We examined the percentage and number of T cell subsets in the thymus and spleen by flow cytometry (FCM). At day 8 after lymphocytic choriomeningitis virus (LCMV) infection, the proportions of T cell subsets, virus-specific CD8⁺ T cells and IFN-γ secreting T cells were analyzed. The viral load in the spleen was measured using qPCR. Naive CD4⁺ T cells (CD4⁺CD25^-CD44^-CD62L⁺) were sorted by flow cytometry to perform T helper cell differentiation in vitro. 【Results】 The percentage and number of T cells in the thymus and spleen of KO mice showed no significant change compared with those in the control group (Arntl^F/FCD4cre^- mice, WT) (P>0.05). Acute LCMV infection did not cause observable changes in effector T cell proportion in the spleen of KO mice compared to that in WT mice (P>0.05), but KO mice showed a higher proportion of IFN-γ secreting T cells (P<0.05) and better virus clearance (P<0.05). In addition, naive CD4⁺ T cells from KO mice were more prone to differentiate into Th1 cells in vitro (P<0.05). 【Conclusion】 Arntl deletion in T cells does not affect T cell development, but enhances their ability to defend against viral infection by promoting Th1 cell differentiation and response.

Objective:To investigate the effect of treatment with orchiopexy at different ages on the clinical outcomes of nonobstructive azoospermia (NOA) patients with a history of cryptorchidism who underwent microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI).Methods:NOA patients undergoing microTESE combined with ICSI from December 2013 to August 2019 in the ICSI treatment cycle in Assisted Reproduction Center of Northwest Women and Children's Hospital were collected in this retrospective cohort study. According to the history of cryptorchidism, the patients were divided into cryptorchidism group and non-cryptorchidism group. The sperm retrieval rates (SRRs) were assessed between these two groups. Then, based on the timing of treatment with orchiopexy, the NOA patients with orchidopexy were subdivided into prepubertal group and pubertal-postpubertal group. The SRRs and the pregnancy outcomes were also assessed.Results:There were 34 NOA patients with cryptorchidism and 604 NOA patients without cryptorchidism underwent microTESE. The SRRs in NOA patients with or without cryptorchidism were 85.3% (29/34) and 40.2% (243/604), respectively. The differences were statistically significant ( P<0.001). In the prepubertal surgery group, sperm was detected in 17 cases, while in the pubertal-postpubertal surgery group, the sperm was detected in 12 cases. The differences were statistically significant ( P=0.044). The total clinical pregnancy rate of cryptorchidism NOA patients treated with ICSI was 65.4% (17/26). Among these individuals, the clinical pregnancy rate of the prepubertal group was 62.5% (10/16) and the pubertal-postpubertal group was 70.0% (7/10). There were no statistical differences in clinical pregnancy rate. Some other clinical pregnancy outcomes, including miscarriage rate in early pregnancy, the rate of cycle with 2PN and the rate of cycle with top-quality embryo, also showed no differences between the two groups. In pathology analysis, all the cryptorchidism NOA patients with failure sperm retrieval were Sertoli cell only syndrome (SCOS). The pubertal-postpubertal group had a significant higher morbidity of SCOS [76.5% (13/17)] compared with the prepubertal group [35.3% (6/17)] ( P=0.016). In addition, the volume of testis, the level of follicle-stimulating hormone and testosterone were not statistically associated with SRR. Conclusion:The SRR of NOA patients with cryptorchidism was higher than those without cryptorchidism. The age at orchidopexy operation may have little effect on the pregnancy outcome of ICSI. It may be more beneficial for microTESE to obtain sperm by undergoing orchiopexy as early as possible.

Objective:To investigate the effect of treatment with orchiopexy at different ages on the clinical outcomes of nonobstructive azoospermia (NOA) patients with a history of cryptorchidism who underwent microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI).Methods:NOA patients undergoing microTESE combined with ICSI from December 2013 to August 2019 in the ICSI treatment cycle in Assisted Reproduction Center of Northwest Women and Children's Hospital were collected in this retrospective cohort study. According to the history of cryptorchidism, the patients were divided into cryptorchidism group and non-cryptorchidism group. The sperm retrieval rates (SRRs) were assessed between these two groups. Then, based on the timing of treatment with orchiopexy, the NOA patients with orchidopexy were subdivided into prepubertal group and pubertal-postpubertal group. The SRRs and the pregnancy outcomes were also assessed.Results:There were 34 NOA patients with cryptorchidism and 604 NOA patients without cryptorchidism underwent microTESE. The SRRs in NOA patients with or without cryptorchidism were 85.3% (29/34) and 40.2% (243/604), respectively. The differences were statistically significant ( P<0.001). In the prepubertal surgery group, sperm was detected in 17 cases, while in the pubertal-postpubertal surgery group, the sperm was detected in 12 cases. The differences were statistically significant ( P=0.044). The total clinical pregnancy rate of cryptorchidism NOA patients treated with ICSI was 65.4% (17/26). Among these individuals, the clinical pregnancy rate of the prepubertal group was 62.5% (10/16) and the pubertal-postpubertal group was 70.0% (7/10). There were no statistical differences in clinical pregnancy rate. Some other clinical pregnancy outcomes, including miscarriage rate in early pregnancy, the rate of cycle with 2PN and the rate of cycle with top-quality embryo, also showed no differences between the two groups. In pathology analysis, all the cryptorchidism NOA patients with failure sperm retrieval were Sertoli cell only syndrome (SCOS). The pubertal-postpubertal group had a significant higher morbidity of SCOS [76.5% (13/17)] compared with the prepubertal group [35.3% (6/17)] ( P=0.016). In addition, the volume of testis, the level of follicle-stimulating hormone and testosterone were not statistically associated with SRR. Conclusion:The SRR of NOA patients with cryptorchidism was higher than those without cryptorchidism. The age at orchidopexy operation may have little effect on the pregnancy outcome of ICSI. It may be more beneficial for microTESE to obtain sperm by undergoing orchiopexy as early as possible.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective:To investigate the clinical outcome of microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) in patients with nonobstructive azoospermia (NOA) associated with mumps orchitis.Methods:The clinical data of NOA patients who underwent microTESE from December 2013 to October 2019 in the ICSI treatment cycle in Assisted Reproduction Center, Northwest Women and Children's Hospital were collected. All the patients who had a history of mumps were divided into two groups according to whether they had mumps orchitis or not. The clinical outcomes after the implementation of microTESE combined with ICSI were compared.Results:A total of 52 NOA patients were finally collected in the present study and 26 patients successfully processed sperm retrieval, the total sperm retrieval rate (SRR) was 50.0% (26/52). The SRR was 94.4% (17/18) in ornitis group, and 26.5% (9/34) in non-ornitis group. The difference between the two groups was statistically significant ( P<0.001). ICSI treatment was tried in sperm patients, and the clinical pregnancy rate was 61.5% (16/26). There was no statistically significant difference in the clinical pregnancy rate and the early pregnancy abortion rate between ornitis group and non-ornitis group [58.5% (10/17) vs. 66.7% (6/9), P=0.696; 20.0% (2/10) vs. 16.7% (1/6), P=0.868]. In the laboratory data, the difference of two pronucleus rate between orchitis group and non-orchitis group was statistically significant (73.9% vs. 57.0%, P=0.006), while the difference of high-quality embryo rate between the two groups was not statistically significant (44.2% vs. 56.8%, P=0.144). Conclusion:The SRR of NOA patients with mumps orchitis was higher that of out ornitis. And good results can be expected when microTESE and ICSI treatment are performed at the same period.

Objective:To investigate the clinical outcome of microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) in patients with nonobstructive azoospermia (NOA) associated with mumps orchitis.Methods:The clinical data of NOA patients who underwent microTESE from December 2013 to October 2019 in the ICSI treatment cycle in Assisted Reproduction Center, Northwest Women and Children's Hospital were collected. All the patients who had a history of mumps were divided into two groups according to whether they had mumps orchitis or not. The clinical outcomes after the implementation of microTESE combined with ICSI were compared.Results:A total of 52 NOA patients were finally collected in the present study and 26 patients successfully processed sperm retrieval, the total sperm retrieval rate (SRR) was 50.0% (26/52). The SRR was 94.4% (17/18) in ornitis group, and 26.5% (9/34) in non-ornitis group. The difference between the two groups was statistically significant ( P<0.001). ICSI treatment was tried in sperm patients, and the clinical pregnancy rate was 61.5% (16/26). There was no statistically significant difference in the clinical pregnancy rate and the early pregnancy abortion rate between ornitis group and non-ornitis group [58.5% (10/17) vs. 66.7% (6/9), P=0.696; 20.0% (2/10) vs. 16.7% (1/6), P=0.868]. In the laboratory data, the difference of two pronucleus rate between orchitis group and non-orchitis group was statistically significant (73.9% vs. 57.0%, P=0.006), while the difference of high-quality embryo rate between the two groups was not statistically significant (44.2% vs. 56.8%, P=0.144). Conclusion:The SRR of NOA patients with mumps orchitis was higher that of out ornitis. And good results can be expected when microTESE and ICSI treatment are performed at the same period.

OBJECTIVETo investigate the profile of promoter methylation and expression of SHP-1 gene in the progression of chronic myeloid leukemia (CML).

METHODSThe expression level of SHP-1 mRNA and protein in bone marrow or peripheral blood mononuclear cells from CML patients were detected by Western blot and SYBR Green-based qRT-PCR. The methylation status of SHP-1 were assessed by methylation-specific polymerase chain reaction (MSP) assay. K562 cells were infected with the lentiviral plasmids pEX-SHP-1-puro-Lv105 (K562-SHP-1) or pEX-EGFP-puro-Lv105 (K562-EGFP). The levels of proteins and phosphorylated proteins were detected by Western blot. qRT-PCR assay was used to test the level of BCR-ABL mRNA.

RESULTSThe relative levels of SHP-1 mRNA were sharply decreased in advanced stages CML compared to chronic phase (CP)-CML (0.79±0.37 vs 1.18±0.64, P= 0.009). The level of SHP-1 protein was lower in advanced stages CML compared to CP-CML (0.57±0.02 vs 1.02±0.04, P=0.039). The frequency of SHP-1 gene promoter methylation at selected loci in CP-CML was 23.8% (10/42), and the methylated regions were detected in all advanced CML samples (P<0.01). SHP-1 was stably transfected into K562 cells and selected with puromycin. Overexpression of SHP-1 inhibited the proliferation and induced the apoptosis of K562 cells, meanwhile leaded to G0/G1 phase arrest. After transfection, the level of BCR-ABL mRNA was not affected in K562-SHP-1 cells (1.32±0.34) compared to K562-EGFP cells (1.18±0.20, P=0.644), but overexpression of SHP-1 caused a slight decrease in BCR-ABL protein in K562-SHP-1 cells compared to K562 -EGFP cells (0.78±0.15 vs 1.27±0.24, P=0.040). Overexpression of SHP-1 resulted in a remarkable decrease in MYC protein, phosphorylated forms of JAK2, STAT5, Akt and MAPK. However, the un-phosphorylated forms of these molecules were not significantly affected.

CONCLUSIONDecreased expression of SHP-1 caused by aberrant promoter hypermethylation may play a key role in the progression of CML by dysregulation of BCR-ABL, Akt, MAPK, MYC, JAK2 and STAT5 signaling.

Apoptosis ; DNA Methylation ; Disease Progression ; Fusion Proteins, bcr-abl ; Humans ; Janus Kinase 2 ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes, Mononuclear ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; RNA, Messenger

Objective To explore the clinical therapeutic value of intracytoplasmic sperm in-jection (ICSI)on retrograde ejaculation-induced male infertility.Methods A total of 10 male pa-tients with retrograde ejaculation-induced male infertility in this center served as research objects. On treatment day,male patients had to urinate immediately after the presence of ejaculation sensa-tion,urine was collected and added with culture medium,centrifuged and cleaned,and directly es-tablish gel to conduct ICSI.As for females,routine gonadotropin-releasing hormone angonist (GnRH-a)was applied to conduct long-protocol controlled ovarian hyperstimulation,and ISCI was conducted for insemination after egg retrival by trans-vaginal puncture.Results All male patients were successfully complete 19-cycle treatment,in which 2 were treated with testicular puncture to collect sperms and ICSI because no movement sperm was found after 4-cycle treatment,while the rest patients finished 15-cycle treatment,including 10 fresh cycles and 5 frozen embryos thawing transplantation (FET)cycles,with total insemination rate,merogenesis rate,clinical pregnancy rate in fresh cycle ,clinical pregnancy rate in FET cycle and total clinical pregnancy rate being 67.97%,94.25%,66.67%,60% and 64.28%,respectively.Conclusion ISCI has certain effi-cacy and is the optimal choice in treating retrograde ejaculation-induced male infertility poor with surgeries.

Objective To explore the clinical therapeutic value of intracytoplasmic sperm in-jection (ICSI)on retrograde ejaculation-induced male infertility.Methods A total of 10 male pa-tients with retrograde ejaculation-induced male infertility in this center served as research objects. On treatment day,male patients had to urinate immediately after the presence of ejaculation sensa-tion,urine was collected and added with culture medium,centrifuged and cleaned,and directly es-tablish gel to conduct ICSI.As for females,routine gonadotropin-releasing hormone angonist (GnRH-a)was applied to conduct long-protocol controlled ovarian hyperstimulation,and ISCI was conducted for insemination after egg retrival by trans-vaginal puncture.Results All male patients were successfully complete 19-cycle treatment,in which 2 were treated with testicular puncture to collect sperms and ICSI because no movement sperm was found after 4-cycle treatment,while the rest patients finished 15-cycle treatment,including 10 fresh cycles and 5 frozen embryos thawing transplantation (FET)cycles,with total insemination rate,merogenesis rate,clinical pregnancy rate in fresh cycle ,clinical pregnancy rate in FET cycle and total clinical pregnancy rate being 67.97%,94.25%,66.67%,60% and 64.28%,respectively.Conclusion ISCI has certain effi-cacy and is the optimal choice in treating retrograde ejaculation-induced male infertility poor with surgeries.