OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Sarcopenia is a progressive syndrome associated with aging, generalized loss of skeletal muscle mass, muscle strength and function.It is closely related to the occurrence of adverse events such as ambulatorydysfunction, falls and fractures in the elderly, and seriously affects the quality of life of the elderly.The etiology of sarcopenia has not been fully elucidated.Various pathophysiological mechanisms such as reduced exercise, genetic factors, age-related hormone changes, malnutrition and insufficient protein intake, decreased neuromuscular function, pro-inflammatory cytokines, and myocyte apoptosis are possible factors.Recent studies have found that intestinal microecological changes may be implicated in the occurrence and development of sarcopenia.In this article, we reviewed intestinal microecological changes and their possible role in the mechanisms underlying sarcopenia.

Advances in genetic testing field have contributed to the boom in carrier screening technology. Expanded carrier screening can effectively identify more high-risk couples than traditional guideline-based carrier screening. The introduction of extended carrier screening has increased the number of referrals for preimplantation genetic testing (PGT) for monogenic disease and enriched the types of disease diagnosed. Expanded carrier screening combined with PGT technology is changing the clinical strategy of genetic risk assessment and preventing birth defects by accurately identifying reproductive risk information and rationalizing fertility planning.

Advances in genetic testing field have contributed to the boom in carrier screening technology. Expanded carrier screening can effectively identify more high-risk couples than traditional guideline-based carrier screening. The introduction of extended carrier screening has increased the number of referrals for preimplantation genetic testing (PGT) for monogenic disease and enriched the types of disease diagnosed. Expanded carrier screening combined with PGT technology is changing the clinical strategy of genetic risk assessment and preventing birth defects by accurately identifying reproductive risk information and rationalizing fertility planning.

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC GSDME-dependent pyroptosis.

OBJECTIVETo evaluate the impact of the concentration of circulating luteinizing hormone (LH) in the late-follicle phase on the outcome of in vitro fertilization for normogonadotrophic women.

METHODSIntracytoplasmic sperm injection treatment was conducted in 432 consecutive cycles of normogonadotrophic women. A stimulation protocol with mid-luteal gonadotropin-releasing hormone (GnRH) agonist down-regulation and ovarian stimulation with follicle stimulating hormone (FSH) was used in all cycles. hMG was added when a follicle of > or = 14 mm was present (FSH + hMG group), not in the control group (FSH-alone). LH and oestradiol concentration in the serum on hCG day were detected. Based on LH levels, patients in the FSH + hMG group were again divided into four subgroups: LH < or = 1, 1 < LH < or = 2, 2 < LH < or = 3, and 3 < LH < or = 10 IU/L.

RESULTSOestradiol concentration on the day of hCG injection in the FSH + hMG group was higher than that in the FSH-alone group [(3435.51 +/- 2029.01) pg/ml vs (2620.62 +/- 1604.80) pg/ml, P < 0.05]. More embryos were transferred in the FSH-alone group than in the FSH + hMG group [(2.77 +/- 0.45) vs (2.22 +/- 0.46), P <0.001]. Fertilization rate, implantation rate, and clinical pregnancy rate were similar between the FSH-alone group and the FSH + hMG group (77.52% vs 78.31%, 41.42% vs 41.68%, 64.56% vs 62.64%, P > 0.05), as well as among the four subgroups of the FSH + hMG group (P > 0.05).

CONCLUSIONThe adding of suitable amount of hMG and physiologically limited LH concentration in the late-follicle phase have no negative effect on the outcome of in vitro fertilization/intracytoplasmic sperm injection for normogonadotrophic women.

Adult ; Down-Regulation ; Estradiol ; blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; therapeutic use ; Follicular Phase ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Luteinizing Hormone ; blood ; Ovulation Induction ; Treatment Outcome

OBJECTIVETo review the treatment results of intracytoplasmic injection of epididymal and testicular sperm obtained from 50 azoospermic patients from January 2003 to May 2004.

METHODSSperm was retrieved by percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) was performed. The rates of successful sperm retrieval, fertilization, implantation and pregnancy were analysed and evaluated.

RESULTSIn the PESA, TESE and ejaculation groups, the number of M II oocytes suitable for ICSI were 286, 360 and 1569 respectively. The difference of fertilization rates among the three groups was not significant (74.8%, 75.2% vs 77.5%, P>0.05). No difference was seen in the implantation and clinical pregnancy rates of the TESE group from the ejaculation group (29.87% vs 29.54%; 48.15% vs 52.60%, P>0.05). However the implantation and clinical pregnancy rates were higher in the PESA group compared with the TESE and ejaculation groups (50.85% vs 29.87%, 29.54%; 68% vs 48.15%, 52.60%, P<0.05). In the PESA group, 17 clinical pregnancies were achieved including 9 ongoing pregnancies, and 6 live deliveries and 2 miscarriages. While in the TESE group, 13 clinical pregnancies were achieved including 4 ongoing pregnancies, 7 live deliveries and 2 miscarriages.

CONCLUSIONICSI with PESA and TESE is an effective method to treat azoospermia.

Adult ; Azoospermia ; therapy ; Epididymis ; Female ; Humans ; Male ; Middle Aged ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; methods ; Testis

OBJECTIVETo investigate the main correlative factors affecting the pregnancy rate of intrauterine insemination (IUI) by means of analyzing 186 patients and 216 cycles of IUI.

METHODSComparisons were made between different pregnancy rates from five respects: infertility reasons, stimulation and natural cycles, different protocols for stimulating ovulation (CC group, CC + hMG group, hMG group), two methods for semen treatment (swim-up and gradient centrifugal), and insemination time (endometrial thickness and E2 levels at the day of hCG injection, and times of IUI).

RESULTSThe pregnancy rates resulting from male and cervix factors (29.82%, 25.00%) were significantly higher than those from other factors. There were few statistical differences in the pregnancy rates between stimulation and natural cycles (19.54% vs 16.67%), between the three different protocols for stimulating ovulation (CC 6.50%, CC + hMG 14.28%, hMG 22.30%), between gradient centrifugal and swim-up methods (20.13% vs 16.13%) and between one-time IUI and two-time IUI (19.73% vs 17.39%) (P > 0.05). However, the pregnancy rates were statistically correlated with the endometrial thickness at the day of hCG injection and different E2 levels of the follicles over 14 mm in diameter (P < 0.05).

CONCLUSIONIUI is of more applied value for infertility caused by male and cervix factors. With these factors in view, to choose the most suitable insemination time is the key to increasing pregnancy rate.

Estradiol ; blood ; Female ; Humans ; Insemination, Artificial ; methods ; Male ; Pregnancy ; Pregnancy Rate ; Time Factors