Qingguang'an-induced autophagy in TFs inhibits scar formation: A follow-up in vivo mechanistic investigation.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang'an group were increased while P62 was downregulated. The LC3-II/Ⅰ ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition. Conclusions: Qingguang'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs.

Gynostemma Glycosides Protect Retinal Ganglion Cells in Rats with Chronic High Intraocular Pressure by Regulating the STAT3/JAK2 Signaling Pathway and Inhibiting Astrocyte and Microglia Activation.

Objective: To observe the protective effect of gynostemma glycosides on retinal ganglion cells in rats with chronically high intraocular pressure. Materials and Methods: A total of 60 rats were randomly divided into group A (the blank group, 10 rats) and chronic high IOP model group (50 rats). The IOP model group (IOP above 22 mmHg) was then randomly divided into an additional 5 groups (10 rats per group): group B (negative control group) treated with normal saline; group C treated with gynostemma glycosides 25 mg/(kg-d); group D treated with gynostemma glycosides 50 mg/(kg-d); group E treated with gynostemma glycosides 100 mg/(kg-d); and group F (positive control group) treated with VitB1 and VitB12. The eyes of each rat were monitored from day 1 to 14 (D1-D14). On day 14, rats were euthanized, after which retinal tissue and optic nerve were examined using real-time PCR, western blot, HE staining, LFB staining, and TUNEL assay. Results: Groups A, C, D, E, and F had significantly lower expression of CD11b, GFAP, Brn3α, and more TUNEL cells than in group B (all P < 0.05). Moreover, the relative expression of STAT3 mRNA and JAK2 (mRNA and protein) in groups A, C, D, E, and F was significantly lower than in group B (P < 0.05), while in group E, the expression was lower than in group D (P < 0.05). Conclusion: Gynostemma glycosides protect retinal ganglion cells in rats with chronically high intraocular pressure possibly associated with the STAT3/JAK2 signaling pathway.

[CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). METHODS: Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). RESULTS: Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. CONCLUSION: The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

[Clinic observation of a levonorgestrel-releasing intrauterine system inserted immediately after artificial abortion].

OBJECTIVE: To compare the contraceptive efficacies and side effects of Mirena (levonorgestrel-releasing intrauterine system, LNG-IUS) inserted immediately after artificial abortion and in the period of regular menstruation. METHODS: A total of 166 female subjects volunteered for the insertion of LNG-IUS. They were divided into 2 groups. Eighty-six female subjects inserted right after artificial abortion were selected as the observation group and 80 female subjects inserted during the period of regular menstruation as the control group. Follow-up was performed at one year after insertion. Contraceptive efficacies and side effects were compared between two groups. RESULTS: No pregnancy was found in both groups. No mirena expulsion occurred in neither groups. The continuation rates were 100%and 95%in the observation and control groups respectively (P > 0.05). The rates of abnormal hemorrhage were 27.5% and 36.2% in observation and control groups respectively during the first three months (P < 0.05). And 22.7% and 23.3% subjects suffered amenorrhea respectively in the first year. No significant difference was found in such side effects as amenorrhea, weight gain, acne and swollen breasts between two groups (P > 0.05). CONCLUSION: Mirena is proved to be an excellent choice for contraception after artificial abortion. Secondary intrauterine surgery may be avoided. And its insertions immediately after artificial abortion or during the period of regular menstruation share the same efficacies.

The influence of early cleavage on embryo developmental potential and IVF/ICSI outcome.

PURPOSE: To observe whether early cleavage can be a predictor of embryo developmental potential, pregnancy and implantation rates. METHODS: A total of 9,544 embryos in 1,095 in vitro fertilization or intracytoplasmic sperm injection cycles were observed with regard to the appearance of early cleavage at 25-29 h post-insemination. RESULTS: A significantly higher proportion of excellent quality embryos were observed in the early cleavage group compared to the late cleavage group (52.5 versus 28.9%, P < 0.01). In the early cleavage group there was also a higher rate of pregnancy per transfer compared with the late cleavage group (38.7 versus 26.3%, P < 0.01). In addition, we found that transfer of only one early cleavage embryo resulted in a high pregnancy rate (38.5%) and a low multiple pregnancy rate (18.0%). CONCLUSION: Early cleavage is a strong indicator of embryo quality, and may be used as an additional criterion in the selection of embryos for transfer to increase pregnancy rate and reduce multiple pregnancy rate.

[Expression of anti-apoptosis livin gene in acute non-lymphocytic leukemia cells and its clinical significance].

To explore the expression of livin gene in acute non-lymphocytic leukemia (ANLL) cells and its clinical significance, the mRNA level of livin gene in 46 ANLL adult patients were measured by using reverse transcription polymerase chain reaction (RT-PCR). Other 10 healthy adults were selected as normal controls (NC), HL-60 cell line was employed as positive control. The results showed that the mRNA level of livin gene in ANLL patients was significantly higher than that in NC, while it decreased in patients with complete remission (CR). In relapsed patients, the level of livin mRNA increased again. In ANLL patients, the CR rate of patients with livin positive was lower than that of patients with livin negative (p<0.05). It is concluded that overexpression of livin gene may play a synergic role in the pathogenesis of ANLL and associates with CR rate in ANLL. It seems that high expression of livin gene may be used as a marker of poor prognosis in acute non-lymphocytic leukemia.