[Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes].

Objective: To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. Methods: A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. Results: All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all P<0.05), and the scores decreased byï¼»M（Q1，Q3）］3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (P<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all P<0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (P<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all P<0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. Conclusion: PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.

[Efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation].

Objective: To assess the efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation. Methods: A total of 89 patients with primary trigeminal neuralgia in Nanjing Drum Tower Clinical College of Xuzhou Medical University from July 2021 to July 2022 were prospectively included, and were divided into experimental group (n=45, modified Hartel approach: selecting 2.0 cm lateral to and 1.0 cm below angulus oris as insertion point) and control group (n=44, traditional Hartel approach: selecting 2.5 cm lateral to the angulus oris as insertion point) according to the random number table method. There were 19 males and 26 females in the experimental group, and aged (67.6±8.8) years. Meanwhile, there were 19 males and 25 females in the control group, and aged (64.8±11.7) years. All the patients were treated by CT-guided radiofrequency thermocoagulation. The success rate of one-time puncture, number of punctures, the time of puncture, operation time, numerical rating scale (NRS) scores and complications were recorded and compared between the two groups. Results: The success rate of one-time puncture in experimental group was 64.4% (29/45), which was higher than that in control group 31.8% (14/44) (P<0.05). The number of punctures [M (Q1, Q3)], the time of puncture [M (Q1, Q3)] and operation time in the experimental group were 1 (1, 2), 218 (206, 378) s, (19.9±2.7) min, which were less than those of control group [2 (1, 3), 390 (231, 598) s, (27.0±3.9) min] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the experimental group were 1 (1, 2), 1 (0, 2) and 1(0, 1), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the control group were 1 (1, 2), 1 (0, 2) and 1 (0, 2), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). There was no statistically significant difference in the incidence of nausea and vomiting, facial numbness, and decreased masticatory muscle strength between the two groups (all P>0.05) In the experimental group, two patients had puncture needles into the oral cavity, with timely detection and replacement of puncture needles, and no infection occurred. There was no cerebrospinal fluid leakage and decreased corneal reflex in both groups. Conclusion: The modified Hartel approach can significantly improve the success rate of one-time puncture via foramen ovale, reduce the operation time and the incidence of postoperative facial swelling, which is a safe and effective puncture method.

[Analysis of clinical features and surgical outcomes of petrous bone cholesteatomas].

Objective: To analyze the clinical features and surgical outcomes of petrous bone cholesteatomas (PBCs). Methods: Data from 39 PBCs patients treated in the Department of Otorhinolaryngology, Xijing Hospital from September 2011 to December 2017 were reviewed retrospectively, including 23 males, 16 femals, aged 12-71 years old, with the median age of 37. Clinical classifications, surgical methods, facial and hearing function, and intraoperative and postoperative complications were made summary analysis. Results: In this study, five patients were congenital PBCs and 34 patients were acquired PBCs. The common clinical symptoms were hearing loss (100%, 39/39), ear discharge/pus (89.7%, 35/39) and facial paralysis (46.2%, 18/39). According to Sanna's classification, 14 cases were supralabyrinthine, including three cases underwent transcochlear (TC) approach, six cases underwent transotic (TO) approach and five underwent translabyrinthine (TL) approach. 10 cases were infralabyrinthine, including eight cases underwent subtotal petrosectomy, one case underwent TO approach and one underwent TL approach.10 cases were massive, including seven cases underwent TC approach, three cases underwent TO approach. Five cases were infralabyrinthine-apical, including two cases underwent TC approach, two cases underwent TO approach, and one case underwent endoscope assisted infratemporal fossa type B. The degree of facial nerve (FN) dysfunction from high to low was massive (6/10), supralabyrinthine (8/14), infralabyrinthine-apical (2/5) and infralabyrinthine (2/10). 19 cases involved in facial nerve operation, three cases underwent FN decompression, four cases underwent FN rerouting, four cases underwent nerve grafting, and one case underwent facial-hypoglossal anastomosis. Preoperative FN involvement in 18 cases, and the FN function was improved in 14 cases after surgery. The improved rate of postoperative FN function was 77.8%. The bone conducted hearing retained 50.0% (14/28) postoperatively. Five cases with cerebrospinal fluid leak were managed by inserting free muscle plugs and cavity obliteration. Two cases with the cholesteatomas matrix involved the sigmoid sinus and the jugular bulb, and occlusion of the sigmoid sinus was performed. Postoperatively, two patients presented with synkinesis. The patients were followed up for 40 to 115 months, and there was no recurrence. Conclusions: There are no specific clinical manifestations for PBCs, thus, it is difficult in early diagnosis and treatment. According to Sanna's classification, preoperative FN and hearing function, the best surgical approach should be selected with minimal recurrences and perioperative morbidity.

[Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases].

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

[Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases].

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

[Application of 3D-printed navigation plate in pulsed radiofrequency therapy of dorsal root ganglion in thoracic postherpetic neuralgia].

Objective: To evaluate the accuracy, efficacy and safety of 3D-printed personalized navigation template in the treatment of thoracic postherpetic neuralgia (PHN) with dorsal root ganglion pulsed radiofrequency (DRG-PRF). Methods: A total of 63 patients with thoracic PHN from March 2019 to December 2020 in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled and randomly divided into study group (n=31) and control group (n=32) by random number table method. The study group received DRG-PRF treatment assisted by 3D-printed navigation template, while the control group received DRG-PRF treatment guided by conventional CT. The one-time success rate of puncture, the incidence of puncture times ≥3, the number of punctures, puncture time, visual analogue scale (VAS) score and surgical complications between the two groups were compared. Results: The one-time success rate of puncture in study group was 84.9% (79/93), which was higher than that of control group [30.2% (29/96)] (P<0.001). The incidence of puncture times ≥3, the number of punctures, puncture time in study group were 4.3% (4/93), 1 (1, 1) and 2.9 (2.8, 3.0) min, respectively, which were lower than that of the control group [21.9% (21/96), 2(1, 3), 9.0 (4.5, 12.9) min, respectively] (all P<0.01). No difference was found in VAS score at each time point before and after surgery between the two groups (all P>0.05). There was one case of pleura puncture in the control group, but no other complications such as straying into vertebral canal, hematoma, spinal cord injury, limb movement disorder, infection were found in the two groups. Conclusions: 3D-printed personalized navigation template is an effective method to guide DRG-PRF for the treatment of thoracic postherpetic neuralgia. It can significantly improve the surgical efficiency of DRG-PRF, but has no significant effect on the surgical efficacy.

[Study of portal venous pressure gradient to predict high-hepatic encephalopathy-risk population post TIPS].

Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce the portal venous pressure and relieve the clinical complications related to portal hypertension. However, hepatic encephalopathy (HE) is still the main complication post TIPS. Studies have shown that patients over 65 years old with liver function reserve in Child-Pugh grade C are the high-HE-risk group post TIPS, and early TIPS treatment can benefit the survival of these high-risk patients. In this study, TIPS was used to treat 60 cases aged > 65 years old and liver function reserve in Child-Pugh grade C (decompensated liver cirrhosis) with esophagogastric variceal bleeding. The clinical results of 1-year was observed and the porto systemic gradient (PSG) was evaluated. The relationship between the incidence of HE and the PSG of patients with and without HE were compared to evaluate the effect of PSG on the incidence of HE.

[Surgical management of petrous bone cholesteatoma and facial nerve protection].

Objective: To discuss the therapeutic scheme of petrous bone cholesteatoma(PBC) and the technique of facial nerve reconstruction. Method: The data of 28 patients who underwent surgery for PBC in our center were analyzed retrospectively. All patients were diagnosed radiologically with PBCs and reconfirmed pathologically after surgery. The surgical approach was discussed basing Sanna's classification of PBCs, and the facial nerve outcomes were analyzed moreover. Result: PBC cases 11 were supralabyrinthine, 4 infralabyrinthine, 3 infralabyrinthine-apical, 10 massive and none apical. The facial nerve was involved in 50% of the cases. The translabyrinthine approach were used in 3 cases. The transotic approach was used in 7 cases in this series.The transcochlear approach type was applied in 12 cases. The Infratemporal fossa type B approach and subtotal petrosectomy were employed in 2 cases and 4 cases respectively. Active management of the nerve(rerouting, anastomosis, or grafting) was required in 14 cases, postoperative facial nerve function were inproved in 10 cases(71.43%). Conclusion: The appropriate surgery approach was vitally important to radical disease clearance in PBCs. The facial nerve preservation was preceded hearing preservation. Active facial nerve management were beneficial to facial nerve recovery..

MiR-630 promotes epithelial ovarian cancer proliferation and invasion via targeting KLF6.

OBJECTIVE: MicroRNAs play critical roles in post-translational gene expression. The current study was to investigate the effects of miR-630 in epithelial ovarian cancer. PATIENTS AND METHODS: Thirty epithelial ovarian cancer tissue and thirty normal ovarian tissue samples were collected and were detected miR-630 expression level with qRT-PCR. MiR-630 mimics, inhibitors and negative controls were transfected into SKOV3 and Cell Counting Kit-8 (CCK-8) assay, and transwell experiment were performed to detect the proliferation rate and migration, respectively. The luciferase reporter assay was utilized to identify miR-630's target gene. Balb/c nude mice were utilized to verify the effect of miR-630 in vivo. RESULTS: QRT-PCR showed a significantly high miR-630 expression in epithelial ovarian cancer relative to normal ovarian tissue. The miR-630 overexpression promoted epithelial ovarian cancer cell SKOV3 proliferation and migration. Krüppel-like factor 6 (KLF6) was predicted as the target of miR-630. In vivo study also verified that miR-630 overexpression stimulated ovarian cancer growth. CONCLUSIONS: We propose that targeting miR-630 might be a promising therapeutic approach for ovarian cancer.

A novel HLA-DRB1 allele, DRB1*16:36 identified in a Chinese individual from the Xinjiang region.

A novel class II human leukocyte antigen allele HLA-DRB1*16:36 is described.

Independent and joint effects of the IL-6 and IL-10 gene polymorphisms in pulmonary tuberculosis among the Chinese Han population.

We investigated the association between interleukin (IL)-6 and IL-10 gene polymorphisms and the susceptibility to pulmonary tuberculosis (PTB). DNA samples were obtained from 191 Han Chinese patients with PTB and 191 healthy control subjects. IL-6 (-572, -174, -597) and IL-10 (-1082, -819) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism. The IL-6 -572 C/C and IL-10 -819 T/T genotypes were observed less frequently in the case group than in the control group, with crude odds ratios of 0.591 [95% confidence interval (CI) = 0.381-0.917] and 0.401 (95%CI = 0.257-0.627), respectively. A significant association remained after adjusting for environmental factors in multivariate logistic analysis. The homozygote genotypes of IL-6 -572 and IL-10 -819 had an adjusted OR of 0.565 (95%CI = 0.356-0.898) and 0.341 (95%CI = 0.210-0.553), respectively. These results indicate that the mutant heterozygote IL-10 -1082 A/ G+G/G genotype and the homozygote IL-10 -819 T/T genotype have a combined effect on PTB. These results suggest that the IL-6 -572 C/C and IL-10 -819 T/T genotype polymorphisms are protective factors against PTB.

Enhanced repair effect of toll-like receptor 4 activation on neurotmesis: assessment using MR neurography.

BACKGROUND AND PURPOSE: Alternative use of molecular approaches is promising for improving nerve regeneration in surgical repair of neurotmesis. The purpose of this study was to determine the role of MR imaging in assessment of the enhanced nerve regeneration with toll-like receptor 4 signaling activation in surgical repair of neurotmesis. MATERIALS AND METHODS: Forty-eight healthy rats in which the sciatic nerve was surgically transected followed by immediate surgical coaptation received intraperitoneal injection of toll-like receptor 4 agonist lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24, control group) until postoperative day 7. Sequential T2 measurements and gadofluorine M-enhanced MR imaging and sciatic functional index were obtained over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve stumps were measured and compared between nerves treated with lipopolysaccharide and those treated with phosphate buffered saline. RESULTS: Nerves treated with lipopolysaccharide injection achieved better functional recovery and showed more prominent gadofluorine enhancement and prolonged T2 values during the degenerative phase compared with nerves treated with phosphate buffered saline. T2 values in nerves treated with lipopolysaccharide showed a more rapid return to baseline level than did gadofluorine enhancement. Histology exhibited more macrophage recruitment, faster myelin debris clearance, and more pronounced nerve regeneration in nerves treated with toll-like receptor 4 activation. CONCLUSIONS: The enhanced nerve repair with toll-like receptor 4 activation in surgical repair of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting such improved nerve regeneration.

Multi-walled carbon nanotubes supported Cu-doped ZnO nanoparticles and their optical property.

Multi-walled carbon nanotubes (MWNTs)/Cu-doped ZnO composite powders were prepared by co-precipitation method, and were characterized by X-ray diffraction, electron microscopy, fluorescence spectrum, and ultraviolet spectrum. Experimental results show that the MWNTs can be modified by Cu-doped ZnO nanoparticles with hexagonal wurtzite structure after annealed at 450 °C, and the nanoparticle size is about 15 nm. Two ultraviolet (UV) peaks and a green band centered at about 510 nm are observed in the fluorescence spectrum of MWNTs/Cu-doped ZnO composite powder annealed at 450 °C. Furthermore, MWNTs and Cu doping significantly improve the UV absorption ability of ZnO.

Review: Male systemic lupus erythematosus: a review of sex disparities in this disease.

Although males with systemic lupus erythematosus (SLE) represent 4-22% of all SLE patients, it may not be appropriate that these cases should be subordinated to females with SLE in terms of most health-related issues. Over the past few decades, some distinctive features of male lupus have been observed with regard to genetic and environmental aspects of sex differences, clinical features, and outcome. In addition, recent insights into sex disparities in this disease have brought forth a few plausible and novel pathogenetic hypotheses. This review discusses these findings and sex disparities in SLE that appear to be especially noteworthy and pertinent to our understanding of male SLE.

A clinically relevant orthotopic implantation nude mouse model of human epithelial ovarian cancer--based on consecutive observation.

The aim of this study is to establish an orthotopic implantation nude mouse model of epithelial ovarian cancer (EOC) and observe its biologic features. A human ovarian tumor line SKOV3ipl previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 64 nude mice. Every week eight mice were taken randomly, and the tumor growth pattern and extent of metastatic disease were monitored continuously. Those mice that died of disease were necropsied and the end date was recorded. The orthotopic implanted tumors demonstrated a 100% take rate. Three weeks after implantation the tumors grew fast and weighed 1149 +/- 152 mg, and 5 weeks after implantation the tumors reached a flat stage. The tumors metastasized more often to peritoneum (32/56) and diaphragm (18/56), then to pelvic lymph nodes (11/56) and lung (10/56), and then to the seldom invaded organs including the pancreas, the liver, the contralateral ovary, and the para-aortic lymph node. Eight nude mice became exhausted 7 weeks after implantation and died within 68 days after implantation. Our study, utilizing the SKOV3ipl cell, is the first model of consecutive observation of the process of invasion and metastasis of EOC. It should be useful in understanding the molecular biology of EOC and in the development of therapeutic modalities against metastasis.

Establishment of a subcutaneous model of the human extrahepatic bile duct carcinoma in nude mice via transplantation of histologically intact tumor tissue.

The purpose of the study was to establish the subcutaneous model of human extrahepatic bile duct carcinoma in nude mice so as to provide a suitable model for the study of extrahepatic bile duct carcinoma. Surgical specimens of the patient with extrahepatic bile duct carcinoma were transplanted into the subcutaneous layer of nude mice. Growth curve of transplanted tumors was drawn and its morphological and biological characteristics, as well as choromosome were observed. A well differentiated mucinous adenocarcinoma model of human bile duct carcinoma in nude mice, designated as HBDCM1-ZSH (Human Bile Duct Carcinoma Model No. 1 established by Zhong Shan Hospital in April, 2001), was established via subcutaneous transplantation of the surgically resected tumor from a 56-year-old Chinese man. HBDCM1-ZSH has been maintained for 13 passages and exhibited 98.1% transplantability. Mean latent periods were 26 days. Transplanted tumors exhibited the characteristics of the original tumor in morphology and biology. Chromosomal analysis revealed numerical abnormalities ranging from 67 to 84. HBDCM1-ZSH expressed carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, cytokeratin (CK7, CK19, CK20), PCNA, AB and PAS. In conclusion, HBDCM1-ZSH is similar to human extrahepatic bile duct carcinoma and provides an applicable animal model for research on extrahepatic bile duct carcinoma.

6-Carboxymethyl genistein: a novel selective oestrogen receptor modulator (SERM) with unique, differential effects on the vasculature, bone and uterus.

The novel genistein (G) derivative, 6-carboxymethyl genistein (CG) was evaluated for its biological properties in comparison with G. Both compounds showed oestrogenic activity in vitro and in vivo. On the other hand G and CG differed in the following parameters: (i) only CG displayed mixed agonist-antagonist activity for oestrogen receptor (ER) alpha in transactivation assays and (ii) only CG was capable of attenuating oestrogen (E(2))-induced proliferation in vascular smooth muscle cells and of inhibiting oestrogen-induced creatine kinase (CK) specific activity in rat tissues. On the other hand only G enhanced the stimulatory effect on CK specific activity in the uterus. In comparison to the selective oestrogen receptor modulator (SERM) raloxifene (RAL), CG showed the same selectivity profile as RAL in blocking the CK response to E(2) in tissues derived from both immature and ovariectomized female rats. Molecular modelling of CG bound to the ligand binding domain (LBD) of ERbeta predicts that the 6-carboxymethyl group of CG almost fits the binding cavity. On the other hand, molecular modelling of CG bound to the LBD of ERalpha suggests that the carboxyl group of CG may perturb the end of Helix 11, eliciting a severe backbone change for Leu 525, and consequently induces a conformational change which could position Helix 12 in an antagonist conformation. This model supports the experimental findings that CG can act as a mixed agonist-antagonist when E(2) is bound to its receptors. Collectively, our findings suggest that CG can be considered a novel SERM with unique effects on the vasculature, bone and uterus.