[Radiographic diagnosis of distal fibula avulsion fractures: Comparison of ankle X-ray and three-dimensional reconstruction of CT].

OBJECTIVE: To investigate the difference in sensitivity between X-ray and three-dimensional reconstruction of computed tomography (3D-CT) for the diagnosis of distal fibular avulsion fracture, and the radiographic presentation of the ossicle. METHODS: From January to October 2018, 92 patients with distal fibular avulsion fracture were visited for surgical treatment in Department of Sports Medicine, Peking University Third Hospital, and 60 cases were finally enrolled according to the inclusion and exclusion criteria. Intraoperative detection was regarded as the gold standard, and the diagnostic sensitivity of preoperative ankle X-ray and 3D-CT for the distal fibular avulsion fractures was statistically determined. The ossicle maximum diameter as well as the degree of its displacement were also measured. On 3D-CT, the distance from the ossicle center point to the anterior fibular tuberosity (a), the distance to the fibular tip (b), and the a/b value was used to present the ossicle displacement. RESULTS: Among the 60 patients, 36 and the 52 patients were correctly detected by X-ray and 3D-CT, respectively, and the sensitivities was 60.0% and 86.7%, respectively (P=0.004). The mean diameter of the ossicle on X-ray and 3D-CT was (9.2±3.9) mm and (10.5±3.2) mm, respectively. The mean distance from the ossicle center to the anterior fibular tuberosity (a) was (17.5±3.6) mm and the mean distance to the fibular tip (b) was (17.4±4.8) mm, with mean a/b values of 1.1±0.7. The intraclass correlation coefficients (ICC) for each measurement ranged from 0.891-0.998 with a high degree of consistency. CONCLUSION: Compared with X-ray, 3D-CT has higher sensitivity in diagnosing distal fibular avulsion fractures, can help clinicians evaluate ossicle's location and choose surgical methods, and is recommended to be performed in patients with suspected distal fibula avulsion fractures in clinical practice.

[Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19].

OBJECTIVE: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19). METHODS: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups. RESULTS: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043). CONCLUSION: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

Limited clinical utility of genotype-guided warfarin initiation dosing algorithms versus standard therapy: a meta-analysis and trial sequential analysis of 11 randomized controlled trials.

In terms of inconsistent conclusions across all relevant randomized controlled trials (RCTs) and available meta-analyses, we aimed to use a meta-analysis and trial sequential analysis (TSA) to evaluate whether clinical utility of a genotype-guided warfarin initiation dosing algorithm could be better than that of a standard therapy regimen, and whether currently relevant evidence could be reliable and conclusive. Overall, 11 eligible RCTs involving 2677 patients were included for further analyses. Compared with fixed dose or clinically adjusted warfarin initiation dosing regimens, genotype-guided algorithms significantly increased time in therapeutic range, shortened time to first therapeutic international normalized ratio (INR) and time to stable doses, but did not show any marked improvements in excessive anticoagulation, bleeding events, thromboembolism, or all-cause mortality. Subgroup analyses revealed that, genotype-guided algorithms showed better control in the outcomes of time in therapeutic range or excessive anticoagulation than fixed-dose regimens rather than clinically adjusted regimens. Except for excessive anticoagulation, currently available evidence of all other outcomes was unreliable and inconclusive as determined with TSA. Our findings suggest that genotype-guided warfarin initiation dosing algorithms have superiority in the improvement of surrogate quality markers for anticoagulation control, but that this does not translate into statistically significant differences in clinical outcomes, which is largely because of the insufficient sample size in the RCTs analyzed.

Immunocytochemical colocalization of progesterone receptor and prolactin in individual stromal cells of human decidua.

Progesterone stimulates decidual PRL production. However, decidualized tissue, in which a high level of PRL is present, features a relatively low level of progesterone receptor (PR) expression. The discrepancy has to be explored at the individual cell level. The present study employed a double labeling method to colocalize PR and PRL in human decidua to examine the correlation between these two proteins. In frozen sections, decidual stroma presented two kinds of cell, which differed in PRL staining. Decidualized cells were positively stained with PRL in cytoplasm and displayed a large cell size and a clear cell outline. Nondecidualized cells showed no specific PRL staining and no clear cell boundary. In decidual stroma, PR staining was exclusively localized in the nuclei, with variations in intensity. When double staining with PR and PRL was performed, these two types of cells demonstrated diverse staining patterns. The PRL-producing cells exhibited weak PR staining, whereas PRL-negative cells evidenced stronger PR staining. In RU 486-treated samples, decidual stroma became less stained with PRL, compared with the control, and fewer cells displayed typical morphology of decidualization, whereas PR staining in the tissue became more extensive and intensive. Double labeling disclosed that the cells with enhanced PR staining were coupled to weaker PRL immunoreaction. Our data suggested an inverse relationship between PRL and PR in individual stromal cells in vivo, which could be reversed by antiprogestin treatment. A possible autocrine mechanism controlling this phenomenon was proposed and deserves further study.

Estrogen and progesterone receptors in human decidua after RU486 treatment.

OBJECTIVE: To examine RU486 action on decidua at the level of cellular estrogen receptor (ER) and P receptor (PR). DESIGN: Controlled basic study for contragestion mechanism of mifepristone. SETTING: Normal human volunteers in an academic research environment. PATIENTS: Sixty women with 6 to 7 weeks of gestation who voluntarily requested termination of pregnancy were recruited and randomly divided into three groups. INTERVENTION: A single dose of 200 mg RU486 was orally administered to the two treatment groups 12 and 24 hours, respectively, before surgical interruption of pregnancies. Placebo was used for control group. Decidual tissues were collected right after operation. MAIN OUTCOME MEASURE: Immunocytochemical reactions of PR and ER in decidua after RU486 treatment were compared with the control subjects. The differences of the reaction in decidual area with or without trophoblast invasion were noted. RESULTS: RU486 treatment increased PR and ER staining in vessel and stroma of decidua without trophoblast invasion (decidua parietalis) but not in decidua with trophoblast invasion (decidua capsularis or basalis). Chi-squared analysis indicated a significant increase in the number of ER-positive samples after RU486 treatment. CONCLUSION: The decidua parietalis was the primary target site of RU486. The lack of RU486 effect on decidua capsularis implied that trophoblast invasion prevented against antiprogestin impact.

PIP: In China, physicians randomly placed 60 pregnant women of 6-7 weeks gestational age into a group receiving one oral dose of RU-486 12 or 24 hours before undergoing vacuum aspiration or into a group receiving a placebo. Aspirate samples were submitted to a laboratory to determine the effect of Ru-486 on progesterone (P) and estrogen (E) receptors in human decidua. RU-486 multiplied P and E receptor staining in vessel and stoma cells of decidua (decidua parietalis) without fetal trophoblast invasion (89% for 12-hour group and 84% in 24-hour group vs. 26%; p M .005). This did not occur, however, in decidua with fetal trophoblast invasion (decidual capsularis or basalis). These findings confirmed the hypothesis that the P antagonist, RU-486, increases P and E receptor levels in decidual tissue. Further, the findings indicated that the contragestive mechanisms of RU-486 is directed at the maternal endometrium and not at the developing embryo or those interfacing cells which anchor it to the endometrium. In fact, the cytological barrier inhibits antiprogestin effects and may even play a role in protecting against spontaneous abortion.

Tissue and serum levels of steroid hormones and RU 486 after administration of mifepristone.

The present study was designed to examine the effect RU 486 administration on steroid hormone levels in serum and decidua. Sixty women at 6-7 weeks gestation were divided into three groups. The first group took a placebo 24 hours before interruption of pregnancy. The other two groups took 200 mg mifepristone 12 and 24 hours before the surgical procedure, respectively. The concentrations of steroids and mifepristone were measured by radioimmunoassay or high performance liquid chromatography. Mifepristone treatment increased the levels of estradiol, cortisol and testosterone in serum and decidual cytosol (p < 0.05 or p < 0.01). A minor elevation in progesterone level was observed but was not statistically significant. The tissue levels of progesterone, estradiol and testosterone were much higher than the serum levels, whereas RU 486 concentration in the tissue was only one-third of the serum level. In addition, the RU 486 level in decidual cytosol was of the same order as that of progesterone. This competitive concentration was not achieved in chorionic villi in our previous observation, explaining why mifepristone exerts its predominant effect on decidua rather than villi. It is concluded that RU 486 reached an effective inhibitory concentration in decidua and had significant effects on the endocrine milieu.

Observation of the activity of factor VIII in the endometrium of women pre- and post-insertion of three types of IUDs.

The endometrial materials were obtained from 90 women who had been randomly inserted with three types of IUDs (Stainless steel ring, SS; copper T 220, TCu 220, and levonorgestrel-releasing device, LNG). An immunoperoxidase reaction, PAP method, with the antiserum of Factor VIII as the primary antibody, was carried out to detect the Factor VIII activity in the endometrial endothelium pre- (control) and post-insertion of the IUDs. The results revealed that: 1. There was a generalized lower Factor VIII activity in the endometrium of women post-insertion of IUDs (except LNG). 2. Comparison of the Factor VIII activity in the endometrium of women using different types of IUDs showed that the TCu type and the SS type decreased the activity significantly whereas the activity remained unchanged after 3-6 months' use of the LNG-IUD. The different types of IUDs seemed to influence the coagulation regulatory system in different ways; the lower Factor VIII activity, the more tendency to bleeding. 3. The Factor VIII activity in the endometrium of women using IUDs was lower in all phases of the menstrual cycle including the proliferative phase when the Factor VIII activity is normally high. It cannot be excluded that this could be a contributing factor to IUD-induced bleedings.

Autoradiographic localization of [3H]RU 486 and [3H]progesterone in the uterus, pituitary and hypothalamus of the rat.

Twenty-one castrated oestrogen-primed Wistar rats, which were 2-months-old, were injected via the jugular vein with 100 microCi/100 g body weight of [3H]RU 486 or [3H]progesterone. Some of these received unlabelled compounds for competition studies. Samples of reproductive tract, pituitary and hypothalamus were excised after 15 min. The 4-micron frozen sections were processed for thaw-mounted autoradiography. The exposure time of the autoradiogram was approximately 6 months. After the injection of [3H]RU 486 and [3H]progesterone, the nuclear concentration of radioactivity was most distinct in muscular and stromal cells of the uterus, and the epithelial nuclei of lumina and glands showed weak labelling. Nuclear localization was also observed in muscle cells of the vagina, cervix and oviduct. After injection of [3H]progesterone, the radioactivity was found in the nuclei and cytoplasm of anterior pituitary cells and some cells showed a preferential nuclear concentration of radioactivity. The distribution of [3H]RU 486 in the anterior pituitary was more extensive than that of [3H]progesterone. In the hypothalamus, specific localization of [3H]RU 486 and [3H]progesterone existed in neurones accumulated in the preoptic nucleus, preoptic suprachiasmatic nucleus and the periventricular nucleus. No localization was found in the diaphragm. Pretreatment with RU 486, but not with dexamethasone, reduced the nuclear concentration of radioactivity of [3H]progesterone in the vagina, uterus, oviduct, pituitary and hypothalamus. The nuclear concentration of radioactivity after injection of [3H]RU 486 was also decreased by preinjection with progesterone. The autoradiographic results suggest that RU 486 and progesterone competed for the specific binding site (possibly a progesterone receptor) in the target cells at the levels of the uterus, pituitary and hypothalamus in vivo.

Autoradiographic localization of [3H]RU 486 and [3H]progesterone in the uterus, pituitary and hypothalamus of the rat.

Twenty-one castrated oestrogen-primed Wistar rats, which were 2-months-old, were injected via the jugular vein with 100 mu Ci/100 g body weight of [3H]RU 486 or [3H]progesterone. Some of these received unlabelled compounds for competition studies. Samples of reproductive tract, pituitary and hypothalamus were excised after 15 min. The 4-microns frozen sections were processed for thaw-mounted autoradiography. The exposure time of the autoradiogram was approximately 6 months. After the injection of [3H]RU 486 and [3H]progesterone, the nuclear concentration of radioactivity was most distinct in muscular and stromal cells of the uterus, and the epithelial nuclei of lumina and glands showed weak labelling. Nuclear localization was also observed in muscle cells of the vagina, cervix and oviduct. After injection of [3H]progesterone, the radioactivity was found in the nuclei and cytoplasm of anterior pituitary cells and some cells showed a preferential nuclear concentration of radioactivity. The distribution of [3H]RU 486 in the anterior pituitary was more extensive than that of [3H]progesterone. In the hypothalamus, specific localization of [3H]RU 486 and [3H]progesterone existed in neurones accumulated in the preoptic nucleus, preoptic suprachiasmatic nucleus and the periventricular nucleus. No localization was found in the diaphragm. Pretreatment with RU 486, but not with dexamethasone, reduced the nuclear concentration of radioactivity of [3H]progesterone in the vagina, uterus, oviduct, pituitary and hypothalamus. The nuclear concentration of radioactivity after injection of [3H]RU 486 was also decreased by preinjection with progesterone. The autoradiographic results suggest that RU 486 and progesterone competed for the specific binding site (possibly a progesterone receptor) in the target cells at the levels of the uterus, pituitary and hypothalamus in vivo.

The effect of RU 486 on progesterone receptor in villous and extravillous trophoblast.

A total of 60 women with 6-7 weeks' amenorrhoea were randomly allocated to three groups. The women in the first group (control) took a placebo 24 h before undergoing vacuum aspiration. The subjects in the second and third groups were given orally 200 mg of RU 486, 12 or 24 h before surgical interruption of their pregnancy. Villi and decidua were collected and frozen in liquid nitrogen. There were no significant differences in villous cytosolic steroid concentrations between the control and RU 486-treated groups. The RU 486 concentration was lower in villous cytosol than in decidua and serum. The immunostaining of progesterone receptor in villous and extravillous trophoblast was weak and localized in both cytoplasm and nucleus. RU 486 treatment had no effect on the immunostaining of progesterone receptors in trophoblast populations except in the placental bed giant cells, where the weak and diffuse progesterone receptor staining in the cytoplasm of controls seemed to be concentrated in the nucleus after RU 486 treatment. In conclusion, RU 486 might have no effect on the immunostaining of progesterone receptor and on steroid concentrations in villi in vivo.

Immunohistochemical localization of progesterone receptor in human decidua of early pregnancy.

Rat monoclonal antibodies to human progesterone receptor were used for immunolocalization studies in human decidua of early pregnancy. Frozen sections of 42 specimens of decidua were stained by the peroxidase-antiperoxidase method (PAP). Progesterone receptor was localized exclusively in the nuclei of decidual and myometrial cells with no specific staining in the cytoplasm. In the decidualized endometrium, stroma were always positively stained. Smooth muscle, pericyte and endothelial cells of blood vessels were extensively stained. Glandular epithelia showed variation in staining, which was positive in the basal but very weak or negative in the superficial layer of the decidua. No specific staining could be detected in the control sections. Of special interest was the positive staining of the endothelium of decidual blood vessels, a finding which has not been reported previously. The cells of the inner lining of vessels that stained with the antiprogesterone receptor antibodies were also Factor VIII positive, thus confirming the endothelial nature of these cells. It is concluded from these results that endothelial cells from human first trimester decidua express progesterone receptors.

Early changes of affinity and binding sites of progesterone and oestrogen receptors in decidua exposed to RU 486.

Sixty patients with 6-7 weeks of amenorrhoea were randomly allocated to three groups. The women in the first group (control) took a placebo 24 h before undergoing a vacuum aspiration. The patients in the second and third groups were given 200 mg of RU 486 orally, 12 or 24 h before surgical interruption of their pregnancy. Decidua were collected and frozen in liquid nitrogen. By Scatchard plot analysis, the number of cytosolic binding sites (1798 +/- 803 fmol/mg DNA) of progesterone in decidua in the control group was significantly reduced (P less than 0.01) to 696 +/- 408 or 626 +/- 179 fmol/mg DNA by RU 486 treatment for 12 or 24 h respectively. The dissociation constants of both cytosolic and nuclear progesterone receptors in RU 486-exposed decidua were increased (P less than 0.01). The number of nuclear binding sites of oestrogen receptor was significantly higher (P less than 0.05) in decidua with RU 486 treatment for 12 h (178 +/- 77 fmol/mg DNA) compared to the control (89 +/- 32 fmol/mg DNA). The results suggest that RU 486 might regulate progesterone and oestrogen receptors in the decidua of early human pregnancy, either directly or indirectly.

Progesterone receptor immunoreactivity at the maternofetal interface of first trimester pregnancy: a study of the trophoblast population.

The aim of our study was to localize oestrogen receptor (ER) and progesterone receptor (PR) in the trophoblast population at the maternofetal interface in early pregnancy. Rat monoclonal antibodies to human ER and PR were used to study 44 cases of chorionic villi and 82 cases of decidua using an immunocytochemical method. The PR-immunoreactive products were localized in the nuclei of syncytiotrophoblast and cytotrophoblast cells of the villi. Specific staining was also present in the cytoplasm. Villous stroma and vessels were stained occasionally. Using cytokeratin staining in an adjacent section or double staining with PR and cytokeratin, the distribution of invading trophoblast cells and their PR expression were examined. In decidual stroma, a type of interstitial cell was identified which simultaneously expressed cytokeratin and PR in the cytoplasm, indicating that the invading trophoblast cells may express PR. All extravillous populations at the interface were positive for PR, including the syncytial lining of the decidual surface, the cytotrophoblast column, the cytotrophoblast shell and the interstitial trophoblast. The immunoreactivity of PR was also localized in the nuclei of vascular endothelial cells, whereas Factor VIII was localized in the cytoplasm of the same cells, thus confirming their endothelial nature. In contrast to PR, little ER could be detected in the trophoblast cell population using anti-ER antibody D75 in our study.

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus.

The interaction of genetic and environmental factors can determine an individual's susceptibility to various cancers. We present a hospital-based case-control study, which included 90 patients of esophageal squamous-cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC.