NIR quantitative model trans-scale calibration from small scale to pilot scale via directed DOSC-SBC algorithm.

In order to solve the problem of inapplicability of NIR quantitative models due to the large difference between the modeling samples and the samples to be tested, Directed DOSC-SBC（DDOSC-SBC）algorithm is proposed in this paper based on Direct Orthogonal Signal Correction combined with Slope/Bias Correction (DOSC-SBC) algorithm. To obtain the suitable spectral matrix transfer parameters for the test set during DDOSC spectral preprocessing, several representative test samples in the test set were selected, then the spectral systematic errors between the modeling set and the test set were corrected with the SBC method in order to realize the trans-scale prediction of the NIR quantitative model. NIR data and the critical quality attributes（CQAs）were detected in the small scale and pilot scale pharmaceutical process of the fluidized bed granulation of dextrin and water extraction of honeysuckle. After the small scale model was calibrated via the directed DOSC-SBC algorithm which was guided by representative pilot scale samples, the small scale model was able to predict the pilot scale test samples more accurately. The NIR quantitative model trans-scale calibration from small scale to pilot scale was also successfully realized with a RPD value higher than 3.5 and RSEP value lower than 10%. DDOSC-SBC algorithm is a successful model trans-scale calibrated method that can be applied to NIR real-time monitoring of CQAs in the preparation process of Chinese herbal medicine.

Efficacy and safety of zuranolone in the treatment of major depressive disorder: a meta-analysis.

Objective: This study aimed to systematically review zuranolone's efficacy and safety in treating major depressive disorder (MDD). Methods: We conducted electronic searches in databases like PubMed, Embase, Cochrane, and Web of Science to identify randomized controlled trials using zuranolone for severe depression from study inception to September 15, 2023. Two independent reviewers screened studies, extracted data, and assessed study quality. Our meta-analysis included four studies with 1,454 patients. The findings showed significant improvements with zuranolone across various measures: Hamilton Depression Rating Scale (HAM-D) scores indicated notable alleviation in depressive symptoms (WMD: -2.03; 95% CI: -2.42 to -1.65); the treatment group's HAM-D score response rate was significantly higher than the control group's at day 15 (OR: 1.46, 95% CI: 1.11 to 1.92, P = 0.01). The meta-analysis also revealed higher remission rates for the treatment group compared to the control group at day 15 (OR: 1.68, 95% CI: 1.18 to 2.39, P = 0.03). Additionally, HAM-A scores on day 15 and MADRS scores on day 15 showed improvement, and HAM-D scores for 30 mg zuranolone on different treatment days exhibited improvement (WMD, -2.55; 95% CI, -3.24 to -1.58; P = 0.05). However, analyzing HAM-D scores on day 15 for various zuranolone doses revealed no significant differences. Importantly, zuranolone use was associated with an increased incidence of adverse reactions. Results: Our meta-analysis included four studies with 1454 patients, showing significant improvements with zuranolone across various measures, including HAM-D scores, HAM-A scores, MADRS scores, and specific HAM-D scores for 30 mg zuranolone on different treatment days. However, no significant differences were found in HAM-D scores on day 15 for various doses of zuranolone. Conclusions: Our findings suggest that zuranolone is a promising, simple, and convenient treatment for patients with major depressive disorder, offering potential guidance for clinical practice.

From mating to mama bear: Distinct VMHvl cell types drive female reproductive state-dependent behavior.

In this issue of Neuron, Liu et al. (2022) molecularly identify subsets of estrogen receptor-1-positive neurons within the female ventrolateral subdivision of the ventromedial hypothalamus activated during sexual receptivity versus agonistic behaviors in distinct reproductive states and demonstrate that these subsets control state-dependent changes in social behaviors.

Effects of Transcutaneous Electrical Acupoint Stimulation on Ovarian Responses and Pregnancy Outcomes in Patients Undergoing IVF-ET: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the influence of different transcutaneous electrical acupoint stimulation (TEAS) modes on ovarian responses and pregnancy outcomes in patients with infertility undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Two hundred infertility patients undergoing IVF-ET were divided randomly into experimental groups (TEAS groups: E-I, E-II, E-III, and E-IV, 40 cases each group) and a control group (mock TEAS group, 40 patients) using the random number method. The patients in the experimental groups received TEAS treatment of 20, 30, 40 and 50 mA for the E-I, E-II, E-III and E-IV groups, respectively. The control group received a treatment of 5 mA. TEAS was applied at acupoints of Guanyuan (RN 4), Zhongji (RN 3), Sanyinjiao (SP 6), Zigong (EX-CA 1), and Taixi (KI 13), once a day for 30 min each time for a treatment period of 10-13 d. Treatment effect was assessed using the following indicators: endometrial thickness on the 6th day of gonadotropin treatment (GN6 day), endometrial thickness on the day on chorionic gonadotropin administration (HCG day), number of ovarian follicles on HCG day, number of ova captured, amount of estrogen required for each harvested ova, number of mature ova divided by the total number of ova, percentage of high-quality embryos, and clinical pregnancy. RESULTS: Endometrial thickness in the experimental groups on the HCG day was significantly better than that of the control group after TEAS stimulation (P=0.01). TEAS exhibited a greater impact on the number of ova captured (P=0.003). However, the effect of TEAS stimulation on the high-quality embryo rate and clinical pregnancy in patients was not statistically significant (P>0.05). CONCLUSIONS: TEAS is an effective method in improving the ovarian state. When the stimulus intensity was at 40 mA and above, it could be helpful to improve the patient's endometrial condition and endometrial receptivity and to retrieve more oocytes. (Trial registration No. ChiCTR-TRC-11001780).

Synthesis of a new Ag+-decorated Prussian blue analog with high peroxidase-like activity and its application in measuring the content of the antioxidant substances in Lycium ruthenicum Murr.

A new Prussian blue analog (PBA) that contains three metal elements and has peroxidase-like activity was synthesized by a simple method. Then, AgNO3 solution was added slowly to the PBA solution under continuous stirring. We found that this synthesis method could be used to prepare other PBAs, and that the anchoring of Ag+ on the surface of PBA could enhance the peroxidase-like activity of the material, suggesting potential applications for the Ag+-decorated Prussian blue analog (Ag-PBA) in traditional Chinese medicine. Ag-PBA is a new type of multi-metal cubic nano-enzyme that exhibits good stability and excellent peroxidase-like activity; as such, it could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 and Ag-PBA. We then developed a new method to measure the content of antioxidant substances in Chinese herbs by using the excellent peroxidase-like activity of Ag-PBA. Using the Chinese herb Lycium ruthenicum Murr. as a model compound, we measured the content of the antioxidant substances in Lycium ruthenicum Murr. by this new method. After optimization of reaction temperature, concentrations of TMB and H2O2, and reaction time, the content of the antioxidant substances was measured and calculated in comparison with anthocyanidin standards. The results of the Ag-PBA method and the classical DPPH method were compared by a paired t-test, with no statistically significant difference found between the methods. Hence, these two methods can be used interchangeably, although the Ag-PBA method had the advantages of simplicity, rapidness, and good stability. Moreover, the Ag-PBA method has a low limit of quantification and a shorter reaction time, which are improvements on the DPPH method, and it is not necessary to avoid light. Therefore, we anticipate that the Ag-PBA method may be used widely for the measurement of the content of antioxidant substances in Chinese herbs.

Pain Relief during Oocyte Retrieval by Transcutaneous Electrical Acupoint Stimulation: A Single-Blinded, Randomized, Controlled Multicenter Trial.

Acupuncture has pain-relief effects, but no data were available on the use of transcutaneous electric acupoint stimulation (TEAS) in pain relief during oocyte retrieval. This study was designed to examine the effect of TEAS for pain relief in women undergoing transvaginal ultrasound-guided oocyte aspiration. This single-blinded, multicenter, randomized controlled trial was performed in China between May 2013 and May 2015. The subjects were randomized to mock TEAS and TEAS. TEAS or mock TEAS was administered 30 min before oocyte retrieval until the end of the operation. The primary and secondary endpoints were the pain measured using the visual analog scale (VAS) within 1 min and 1 hour after oocyte retrieval, respectively. Serum ß-endorphin levels were tested in the first 50 patients/group. 390 women were undergoing oocyte retrieval. Pain levels evaluated using VAS within 1 min (18.6 ± 1.3 vs. 24.4 ± 1.7, P < 0.01) and 1 h after oocyte aspiration (4.6 ± 0.7 vs. 6.8 ± 0.8, P < 0.05) were lower in the TEAS group than in the mock TEAS group. Nausea assessment revealed a significantly lower VAS score in the TEAS group within 1 min (1.2 ± 0.4 vs. 2.9 ± 0.7, P < 0.033). Serum ß-endorphin levels were significantly higher in the TEAS group than in the mock TEAS group (11.4 ± 0.5 vs. 9.1 ± 0.4, P < 0.001) after retrieval. Serum ß-endorphin levels were higher in the TEAS group after the procedure than baseline (11.4 ± 0.5 vs. 9.1 ± 0.3, P < 0.001). Oocyte retrieval causes pain and discomfort, but TEAS is effective and safe for suppressing the pain and alleviating nausea associated with the operation.

Effect of Dandelion Extracts on the Proliferation of Ovarian Granulosa Cells and Expression of Hormone Receptors.

BACKGROUND: In the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T-1 (DE-T1) is an effective component of the extract from the leaves and stems of Taraxacum officinale, which is one of the medicines used in some patients with POR, but its molecular mechanism remains unclear. METHODS: Following IVF, ovarian granulosa cells (GCs) of sixty patients were extracted and divided into normal ovarian response (NOR) and POR groups. GCs were cultured in a dose-dependent and time-dependent manner with DE-T1, proliferation of GCs was determined by Cell Counting Kit-8 assay, and mRNA levels of insulin-like growth factor 1 receptor (IGF-1R), luteotropic hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), LHR, and CYP19A1 (aromatase) were determined by quantitative polymerase chain reaction. Progesterone and estradiol (E2) concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: The cell viability gradually increased with the progressive increase in the DE-T1 concentration. Compared with the control group (without DE-T1), the mRNA expressions of FSHR, LHR, IGF-1R, and CYP19A1 were upregulated after the addition of DE-T1, especially in the 2.5% DE-T1 group (P < 0.01). The expression of IGF-1R was upregulated approximately 25 times (24.97 ± 4.02 times) in the POR group with 2.5% DE-T1. E2 and progesterone levels increased with the increasing DE-T1 concentration. There were highly significant differences in the E2 and progesterone secretion between the NOR and POR groups (P < 0.01). CONCLUSION: DE-T1 may promote steroid hormone synthesis by promoting GC proliferation and upregulating GC receptor expression, thereby improving ovarian endocrine function.

Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1G93A mutation.

AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.

The effect of dehydroepiandrosterone supplementation on ovarian response is associated with androgen receptor in diminished ovarian reserve women.

BACKGROUND: Diminished ovarian reserve(DOR) is associated with female infertility and poor response to ovarian stimulation. Our objective was to assess the effect of dehydroepiandrosterone(DHEA) on DOR women and to explore whether the improvement of ovarian response after DHEA supplementation was dependent on the expression levels of androgen receptor(AR). METHODS: A prospective cohort study was performed in the Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital during August 2014 to August 2016. 103 DOR women who completed the study were divided into the DHEA group (n = 53), which received DHEA supplementation (25 mg three times a day) for 8 weeks, and the control group (n = 50), which did not receive DHEA, before the IVF cycles. Serum hormone levels(FSH, LH, E2, T, DHEAs, AMH, INHB), antral follicle count(AFC) and the expression of AR and FSH receptor(FSHR) in granulosa cells(GCs) were measured, meanwhile ovarian response parameters and IVF outcomes were compared. The GCs from another 36 DOR women were cultured with different concentrations of DHEA in vitro. Then, we compared the expression of AR and FSHR in GCs according to the different numbers of oocytes retrieved both in DHEA and control group. RESULTS: In the present study, DHEA supplementation resulted in significantly higher levels of serum T(P = 0.047), DHEAs(P = 0.019) and AR mRNA expression in GCs(P = 0.049). In vitro experiment, the protein and mRNA expression of AR and FSHR in the preovulatory GCs were significantly increased in response to DHEA supplementation(P <0.05). No significant differences were found in ovarian reserve, ovarian response, or IVF outcomes between the two groups. Subgroup analyses showed the levels of AR and FSHR mRNA in GCs were significantly increased in DHEA group with ≥5 oocytes retrieved(P <0.05). CONCLUSION: DHEA supplementation can increase the expression of AR in preovulatory GCs both in vivo and in vitro. The selective beneficial effects of DHEA supplementation on ovarian response in DOR women may depend on the increasing expression of AR and FSHR in GCs. TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( ChiCTR-IPR-15006126 ). Retrospectively Registered 19 March 2015.

Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine: a group consensus.

With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.

Epidemiological investigation of risk factors of the pregnant women with early spontaneous abortion in Beijing.

OBJECTIVE: To determine the risk factors of the pregnant women with early spontaneous abortion in Beijing. METHODS: A total of 34,417 cases of pregnant women were participated in the survey from January 2000 to December 2013. A questionnaire was informed to each woman. The content of questionnaire includes four parts: general condition, obstetrical history, past history and family history, and living environment and habits. The mental condition was evaluated with Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). RESULTS: A total of 32,296 questionnaires were collected. The spontaneous abortion rate in the total sample was 3.0%. There was no significant difference between the normal pregnancy group and spontaneous abortion group in terms of general condition, obstetrical and past history (P>0.05). Significant differences between the two groups were found in terms of decoration during pregnancy, keeping pets, near mobile communication base station within 100 m around the residence, drinking during pregnancy, having a cold during pregnancy and SAS (P<0.05). Having a cold during pregnancy, decoration during pregnancy, near mobile communication base station within 100 m around the residence, keeping pets and high SAS were determined the independent risk factors of spontaneous abortion by Logistic regression analysis. CONCLUSIONS: Having a cold during pregnancy, decoration, keeping pets, near mobile communication base station within 100 m around the residence and high SAS are the independent risk factors of spontaneous abortion in Beijing.

Effect and mechanism of fuzhisan and donepezil on the sirtuin 1 pathway and amyloid precursor protein metabolism in PC12 cells.

The present study aimed to determine the effect and mechanism of fuzhisan (FZS) and donepezil on the SIRT1 signaling pathway and the metabolism of the amyloid precursor protein (APP) in PC12 cells. An experimental cell model of PC12 cells with Aß25­35­induced neurotoxicity was established and cell proliferation was determined by the MTT assay following treatment with donepezil and FZS. In addition, cell apoptosis was determined using DAPI staining and light microscopy. Furthermore, western blot analysis and ELISA were utilized to evaluate the expression levels of associated APP, Aß40, Aß42, sAPPα, sAPPß, ADAM10, sirtuin 1 (SIRT1) and forkhead box O (FoxO) protein. The results indicated that the cell model was successfully established and FZS protected the PC12 cells from the neurotoxic effects of Aß25­35, in a similar effect to donepezil, in a dose­dependent manner. The expression of APP remained at the same level during the experimental period. The levels of Aß40, Aß42 and sAPPß were downregulated, where as sAPPα, ADAM10, SIRT1 and FoxO expression levels were upregulated. In conclusion, FZS treatment attenuated the Aß25­35­induced neurotoxicity in vitro. The neuroprotective mechanism of FZS was determined, including the induction of ADAM10 and SIRT1­FoxO pathway, which participated in the process of neuroprotection. The present study identified the neuroprotective function of FZS, which may protect against Aß­induced toxicity. Therefore, FZS may be used clinically as a beneficial therapeutic drug for the development or progression of Alzheimer's disease.

Effect of Isopropanolic Cimicifuga racemosa Extract on Uterine Fibroids in Comparison with Tibolone among Patients of a Recent Randomized, Double Blind, Parallel-Controlled Study in Chinese Women with Menopausal Symptoms.

Objective. Effect of isopropanolic Cimicifuga racemosa extract (iCR) on uterine fibroid size compared with tibolone. Method. The randomized, double-blind, controlled study in China enrolled 244 patients aged 40-60 years with menopausal symptoms (Kupperman Menopause Index ≥ 15). The participants were treated with either iCR of 40 mg crude drug/day (N = 122) or tibolone 2.5 mg/day (N = 122) orally for 3 months in 2004. Now, we investigated the subset of all women (N = 62) with at least one uterine fibroid at onset of treatment for the effect of iCR (N = 34) on fibroid size compared with tibolone (N = 28) by transvaginal ultrasonography. Results. The median myoma volume decreased upon iCR by as much as -30% (P = 0.016) but increased upon tibolone by +4.7%. The percentage of volume change, mean diameter change and geometric mean diameter change of the iCR group compared to tibolone were statistically significant (P = 0.016, 0.021, 0.016 respectively). Conclusion. Our results suggest that iCR (Remifemin) is a valid herbal medicinal product in patients with uterine myomas as it provides adequate relief from menopausal symptoms and inhibits growth of the myomas in contrast to tibolone.

Effects of low-level organic selenium on lead-induced alterations in neural cell adhesion molecules.

Low-level lead (Pb) exposure has been reported to impair the formation and consolidation of learning and memory by inhibiting the expression of neural cell adhesion molecules (NCAMs) and altering the temporal profile of its polysialylation state. In this study, we investigated whether administration of low-level organic selenium (selenomethionine, Se) at different time points could affect Pb-induced changes of NCAMs in female Wistar rats. Here we reported that the exposure of Se (60µg/kg body weight/day) at different time points significantly alleviated Pb-induced reductions in the mRNA and protein levels of NCAMs, and increases in the mRNA levels of two polysialyltransferases (St8sia II, Stx; St8sia IV, Pst) as well as the sialyltransferase activity (p<0.05). The concentrations of Pb in blood and hippocampi of Wistar rats treated with the combination of Se and Pb were significantly lower than those treated with Pb alone (p<0.05). Our results suggest that low-level organic Se can not only prevent but also reverse Pb-induced alterations in the expression and polysialylated state of NCAMs as well as the concentration of Pb in rat blood and hippocampus.

[Efficacy and safety of remifemin compared to tibolone for controlling of perimenopausal symptoms].

OBJECTIVE: To investigate the efficacy and safety of remifemin (isopropanolic extract of cimicifuga racemosa) treating perimenopausal symptoms in comparison of tibolone. METHODS: One hundred and eighty postmenopausal women at range of 40 - 60 years old were enrolled in a multicenter, randomized and double blind study. They were divided into remifemin and tibolone group at ratio 1:1. The therapeutic strategy was remifemin 20 mg bid po for 12 weeks in remifemin group and tibolone 2.5 mg qd po for 12 weeks in tibolone group. To evaluate therapeutic effect, total score of Kupperman menopause index (KMI) was used as the major observed index and single item score of KMI were secondary observed index. Safety warning was determined by laboratory tests and adverse events at timepoint of before, at 4 and 12 weeks treatment. RESULTS: (1) Total score of KMI: it were 24 +/- 5 in remifemin group and 25 +/- 6 in tibolone group before treatment. At timepoint of 4 weeks treatment, it were 11 +/- 6 in remifemin group and 11 +/- 7 in tibolone group. At timepoint of 12 weeks treatment, it were 7 +/- 6 in remifemin group and 6 +/- 5 in tibolone group. Total KMI score between two groups did not show statistical difference at various timepoint (P > 0.05). (2) Single item score of KMI: when compared before, at 4 and 12 weeks treatment, did show remarkable difference (P < 0.05) either in remifemin or in tibolone group. However, those single items of KMI score did not show statistical difference between 4 and 12 weeks timepoint in each treatment group (P > 0.05). (3) Adverse effect: the incidence of adverse effect in remifemin group was significantly lower than that of tibolone group. None case with vaginal bleeding was observed in remifemin group, however, 17 cases with vaginal bleeding occurred in tibolone group (19%, 17/90). The incidence of breast swelling were 16% (14/90) in remifemin group and 36% (32/90) in tibolone group; before treatment, the thickness of endometrium were (2.6 +/- 1.1) mm in remifemin group and (2.8 +/- 1.1) mm in tibolone group; at timepoint of 12 weeks treatment, the thickness of endometrium were (2.9 +/- 1.4) mm in remifemin group and (3.4 +/- 2.0) mm in tibolone group. In comparison of thickness of endometrium before and at 12 weeks treatment, no remarkable changes was observed in remifemin group, however, endometrium displayed significantly thicker in tibolone group. CONCLUSIONS: Our study suggested that remifemin was one effective and safe agent to manage women with climacteric symptom. It has similar therapeutic effect and lower incidence of adverse effect when compared with tibolone.

Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone.

OBJECTIVE: To investigate the efficacy-safety balance of the isopropanolic extract of Actaea (=Cimicifuga) racemosa (iCR, Remifemin) in comparison with tibolone in Chinese women with climacteric complaints. METHOD: The randomized, double-blind, controlled 3-month study in 5 centers of 3 cities in China enrolled 244 menopausal patients aged 40-60 years and with a Kupperman Menopause Index (KMI)>or=15. The participants were assigned to either iCR corresponding to 40 mg crude drug/day (N=122) or tibolone 2.5mg/day (N=122) orally. The primary endpoint was the combination of the Mann-Whitney values (MWV) of the KMI and the frequency of adverse events (benefit-risk balance) at end of treatment (MWV>0.5 shows superiority; MWV>0.36 shows non-inferiority). RESULTS: KMI decreased from 24.7+/-6.1 to 11.2+/-6.2 and 7.7+/-5.8 (iCR) and to 11.2+/-7.2 and 7.5+/-6.8 (tibolone) at 4 and 12 weeks. This remarkable and clinically relevant improvement was similar in both treatment groups (MWV=0.47; 95% CI=0.39-0.54; p(non-inferiority)=0.002) showing statistical significant non-inferiority of iCR to tibolone. The KMI-responder rate was similar in both groups (84% and 85%). The safety evaluation showed for both groups a good safety and tolerability profile, however, there is a significant lower incidence of adverse events (p<0.0001) in favor of the herbal treatment. None of the postmenopausal iCR patients experienced vaginal bleeding in contrast to tibolone (17 cases). Breast and abdominal pain as well as leukorrhea was mostly observed in the tibolone group (p=0.015, p=0.008, p=0.002). No serious adverse event was observed in the iCR-group, however, two occurred in the tibolone-group. The benefit-risk balance for iCR was significantly (p=0.01) superior to tibolone (MWV=0.56; 95% confidence interval [0.51-0.62]). CONCLUSION: The efficacy of iCR (medicinal product Remifemin) is as good as tibolone for the treatment of climacteric complaints, even for moderate to severe symptoms, whereby iCR is clearly superior regarding the safety profile. This iCR containing medicinal product is an excellent option for treatment of climacteric complaints which has now for the first time been verified in Asian women.

[Cloning and expression of human IL-1R II gene].

AIM: To clone human IL-1R II cDNA and construct its recombinant retrovirus vector so as to explore its role in IL-1R II related diseases. METHODS: Human IL-1R II cDNA was amplified by RT-PCR from peripheral blood mononuclear cells (PBMCs) and inserted into the vector PET22b to construct recombinant vector PET22b-IL-R II. The recombinant was transfected into E. coli BL21 and expressed under IPTG induction. Expressed products were detected by Western blot. In addition, human IL-1R-II cDNA was subcloned into retrovirus vector LZRSPBMN and transfected into 293 cells by calcium phosphate precipitation. IL-1R II expression was detected by immunohistochemical staining. RESULTS: IL-1R II cDNA with 1,203 bp was amplified by RT-PCR from human PBMCs. The recombinant of this cDNA could be expressed in E. coli,which was confirmed by Western blot results. Immunohistochemistry detection showed IL-1R II protein was expressed in 293 cells. CONCLUSION: Human IL-1R II gene was cloned successfully. PET22b-IL-1R II and LZR-IL-1R II were constructed and the recombinant protein IL-1R II was expressed in E.coli BL21. The results reported herein lay the foundation for further research on the role of IL-1R II in certain diseases.