Transoral Thyroidectomy: Safety and Outcomes of 200 Consecutive North American Cases.

BACKGROUND: North American adoption of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been limited due to concerns regarding the generalizability of published outcomes, as data are predominantly from Asian cohorts with a different body habitus. We describe our experience with TOETVA in a North American population in the context of the conventional transcervical approach thyroidectomy (TCA). STUDY DESIGN: Cases of TOETVA and TCA were reviewed from August 2017 to March 2020 at a tertiary care center. Outcomes included operative time, major (permanent recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, hematoma, conversion to open surgery), and minor complications. The TOETVA cohort was stratified into body mass index (BMI) classes of underweight/normal < 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥ 30 kg/m2 for comparative analysis. Multivariable logistic regression analyses were performed for odds of cumulative complication. RESULTS: Two hundred TOETVA and 333 TCA cases were included. There was no difference in incidence of major complications between the TOETVA and TCA cohorts (1.5% vs. 2.1%, p = 0.75). No difference was found in the rate of temporary RLN injury (4.5% vs. 2.1%, p = 0.124) or temporary hypoparathyroidism (18.2% vs. 12.5%, p = 0.163) for TOETVA and TCA, respectively. Surgical technique (TOETVA vs TCA) did not alter the odds of cumulative complication (OR 0.69 95% CI [0.26-1.85]) on logistic regression analysis. In the TOETVA cohort, higher BMI did not lead to a significantly greater odds of cumulative complication, 0.52 (95% CI [0.17-1.58]) and 1.69 (95% CI [0.74-3.88]) for the overweight and obese groups, respectively. CONCLUSION: TOETVA can be performed in a North American patient population without a difference in odds of complication compared to TCA. Higher BMI is not associated with greater likelihood of complication with TOETVA.

[Content determination and principal component analysis of nine active components in Paeonia lactiflora flowers from different cultivars and drying methods].

This study aims to establish an UPLC-DAD method for the simultaneous determination of nine active components in phenolic acids, anthocyanins, monoterpene glucosides and flavonoids in the petals of Paeonia lactiflora flowers from different cultivars and processing methods. UPLC analysis was performed on a Waters ACQUITY UPLC HSS T3 C_(18) column(2.1 mm × 100 mm, 1.8 µm)for gradient elution with a mobile phase consisting of 0.5% formic acid solution(A)-acetonitrile(B)at a flow rate of 0.3 mL·min~(-1).The detection wavelength was determined with a switched wavelength method and the column temperature maintained at 20 ℃, with an injection volume of 2 µL.The contents of the above components in the samples with different sources and treatment methods were obtained. The principal component analysis(PCA)of P. lactiflora flowers was conducted by using SIMCA 14.0 software, and the results showed that the P. lactiflora flowers could be classified into two categories according to cultivars, including P. lactiflora 'Bozhou-shaoyao' as one category with high contents of the above components, P. lactiflora 'Baihuachuanshaoyao' and P. lactiflora 'Honghuachuanshaoyao' as the other category. Dried P. lactiflora flowers could be classified into three categories, including baking-drying, sun-drying and shade-drying, with baking-drying method as the optimal one.The P. lactiflora flowers were not greatly affected by origins, growing altitudes, growing years, or blooming stages.The results of contents determination can be used to guide the cultivar selection, harvest and processing of P. lactiflora flowers.

The Role of Autophagy and the Chemokine (C-X-C Motif) Ligand 16 During Acute Lung Injury in Mice.

BACKGROUND Acute lung injury (ALI) is responsible for mortality in hospitalized patients. Autophagy can negatively regulate inflammatory response, and CXCL16 (chemokine (C-X-C motif) ligand 16) is a kind of chemokine, which is closely related to the inflammatory response. However, the relationship between autophagy and CXCL16 in ALI is still unclear. This study aimed to investigate the role of autophagy and chemokine CXCL16 in ALI in mice. MATERIAL AND METHODS Thirty-two male C57BL/6 mice were divided into four groups. The control group (C group) was given normal saline through intraperitoneal injection. The L group was given LPS (lipopolysaccharide) at 30 mg/kg to construct an ALI model. The 3-MA group received an intraperitoneal injection of inhibitor of autophagy 3-methyladenine at 15 mg/kg, 30 minutes before LPS injection. The anti-CXCL16 group was given 20 mg/kg of CXCL16 monoclonal antibody 30 minutes before the LPS injection. RESULTS In the 3-MA Group, the level of histological analysis, lung wet/dry ratio, total protein of BAL (bronchoalveolar lavage fluid) and TNF-a level were higher than the L group (p<0.05), the level of autophagy was lower than the L group (p<0.05), and the level of CXCL16 was higher than the L group (p<0.05). In the anti-CXCL16 group, the level of histological analysis, lung wet/dry ratio, BAL protein, and TNF-α level were declined compared to the L group (p<0.05), but there was no statistically significant difference in expression of CXCL16 detected by ELISA between the anti-CXCL16 group and the L group (p>0.05). CONCLUSIONS Autophagy played a protective role in ALI induced by LPS in mice. Autophagy could regulate the level of CXCL16. The chemokine CXCL16 could exacerbate ALI.

Pseudoaneurysm formation after valve sparing root replacement in children with Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder predisposing patients to aneurysm formation and arterial dissection. Aortic root replacement is often performed prophylactically and valve-sparing root replacement (VSRR) has become the procedure of choice. However, in these patients with connective tissue disorders, postoperative pseudoaneurysms may develop. METHODS: All children with LDS undergoing VSRR at a single institution were retrospectively reviewed to identify patients who developed postoperative pseudoaneurysms. RESULTS: Thirty-one children with LDS underwent VSRR; four of these developed pseudoaneurysms of their synthetic aortic root grafts requiring reoperation. These four children were reviewed to investigate the cause of pseudoaneurysm formation after VSRR. Each had severe subtypes of LDS. Each underwent reoperation for repair of their pseudoaneurysms and were found to have suffered pseudoaneurysms as a result of tearing of sutures from their reimplantation VSRR. CONCLUSIONS: Pseudoaneurysms following aortic root replacement with VSRR can occur in children with severe subtypes of LDS. Long-term surveillance is required to detect these potentially life-threatening lesions.

Pyro-Borates, Spiro-Borates, and Boroxinates of BINOL-Assembly, Structures, and Reactivity.

VANOL and VAPOL ligands are known to react with three equivalents of B(OPh)3 to form a catalytic species that contains a boroxinate core with three boron atoms, and these have proven to be effective catalysts for a number of reactions. However, it was not known whether the closely related BINOL ligand will likewise form a boroxinate species. It had simply been observed that mixtures of BINOL and B(OPh)3 were very poor catalysts compared to the same mixtures with VANOL or VAPOL. Borate esters of BINOL have been investigated as chiral catalysts, and these include meso-borates, spiro-borates, and diborabicyclo-borate esters. Borate esters are often in equilibrium, and their structures can be determined by stoichiometry and/or thermodynamics, especially in the presence of a base. The present study examines the structures of borate esters of BINOL that are produced with different stoichiometric combinations of BINOL with B(OPh)3 in the presence and absence of a base. Depending on conditions, pyro-borates, spiro-borates, and boroxinate species can be generated and their effectiveness in a catalytic asymmetric aziridination was evaluated. The finding is that BINOL borate species are not necessarily inferior catalysts to those of VANOL and VAPOL but that, under the conditions, BINOL forms two different catalytic species (a boroxinate and a spiro-borate) that give opposite asymmetric inductions. However, many BINOL derivatives with substitutents in the 3- and 3'-positions gave only the boroxinate species and the 3,3'-Ph2BINOL ligand gave a boroxinate catalyst that gives excellent inductions in the aziridination reaction. BINOL derivatives with larger groups in the 3,3'-position will not form either spiro-borates or boroxinate species and thus are not effective catalysts at all.

[Mutations of vitamin D receptor gene found in patients with multiple myeloma].

Objective: To explore the mutations of vitamin D receptor (VDR) gene in patients with multiple myeloma (MM). Methods: Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the mutations of VDR gene(loci Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ, Taq Ⅰ) in forty MM cases and 84 healthy control subjects. Results: A synonymous mutation (ATC→ATA , both encode isoleucine) at cDNA codon1421 of VDR gene was found in one MM patients, which correlated to a better therapeutic response. Rare Bsm Ⅰ AA genotype and Taq Ⅰ CC genotype were detected in a MM patient, which might be related to the relapsing and refracfory disease. Meanwhile, a rare allele(rs201747972, global MAF: A=0.0005/1), was found in another MM patient, which might be related to MM cell lines of two origins. rs11574113 G>C, rs2229829 C>A and rs201747972 C>T polymorphic loci(the same as Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ and Taq Ⅰ) were found in a MM patient, which were associated with nonsense-mediated mRNA decay(NMD), contributing to the onset of MM. Conclusions: A new synonymous mutation, rare genotype, rare allele and new SNP are found in this study. These data enrich the genetic information of MM in China, and are helpful for the further research on MM pathogenesis.

Serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF) which is found in high levels during pregnancy is not higher in women with progesterone (P) receptor (R) positive vs. negative breast cancer.

PURPOSE: To determine if serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF), which is present in high levels during normal pregnancy, is present in higher levels in women with breast cancer positive for progesterone receptors. The study would also determine whether the presence or absence of the estrogen receptor in any way modifies PIBF expression. MATERIALS AND METHODS: PIBF using a research ELISA was evaluated in the follicular phase in 21 women with receptor status as follows: seven with estrogen receptor (ER)+ and progesterone receptor (PR)+, seven with ER- and PR+, and seven with ER+ and PR. RESULTS: The results showed no differences in serum PIBF in the three groups. The serum PIBF levels were no different than historical controls in the follicular phase. CONCLUSIONS: Measurement of serum PIBF does not seem to be an important marker to use to either detect women with breast cancer or to help determine tumor virulence or potential specific therapies. If PIBF plays a role in helping cancer cells to escape immune surveillance, it seems that the intracytoplasmic PIBF would be the form most likely operative.

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer.

BACKGROUND: The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC). METHODS: Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses. RESULTS: Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis. CONCLUSION: Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.

Double stereodifferentiation in the catalytic asymmetric aziridination of imines prepared from α-chiral amines.

The catalytic asymmetric aziridination of imines and diazo compounds (AZ reaction) mediated by boroxinate catalysts derived from the VANOL and VAPOL ligands was investigated with chiral imines derived from five different chiral, disubstituted, methyl amines. The strongest matched and mismatched reactions with the two enantiomers of the catalyst were noted with disubstituted methyl amines that had one aromatic and one aliphatic substituent. The synthetic scope for the AZ reaction was examined in detail for α-methylbenzyl amine for cis-aziridines from α-diazo esters and for trans-aziridines from α-diazo acetamides. Optically pure aziridines could be routinely obtained in good yields and with high diastereoselectivity and the minor diastereomer (if any) could be easily separated. The matched case for cis-aziridines involved the (R)-amine with the (S)-ligand, but curiously, for trans-aziridines the matched case involved the (R)-amine with the (R)-ligand for imines derived from benzaldehyde and n-butanal, and the (R)-amine with the (S)-ligand for imines derived from the bulkier aliphatic aldehydes pivaldehyde and cyclohexane carboxaldehyde.

BRCA2 deficiency increases sensitivity of medulloblastoma to Olaparib by inhibiting RAD51-mediated DNA damage repair system.

PURPOSE: BRCA2 defect exists in glioma and regulates drug resistance of glioma to chemotherapy. However, its role in medulloblastoma and the mechanism is not known. To investigate the effects of BRCA2 deficiency combined with Olaparib in medulloblastoma and the mechanism. METHODS: BRCA2 was knocked down by RNAi technology and cell proliferation was detected by CCK-8 assay. Cell apoptosis was determined by FACS analysis when the in vivo role of BRCA2 was explored with xenograft mice model. Western blotting technology was used to explore the mechanism of BRCA2. RESULTS: Knockdown of BRCA2 enhanced the inhibitory effect of Olaparib on proliferation of Daoy and LN229 cells. The inhibition rate of Olaparib on Daoy or LN229 cells was 61.1%, 66.03% in shBRCA2 group, while it was 42.9%, 41.1% in shNC group. Overexpression of RAD51 partially reversed the effect of shBRCA2. In Daoy cells, apoptotic rate was 26.9% in Olaparib group and 58.9% in Olaparib/shBRCA2 group. However, it was 33.4% after RAD51 was overexpressed. It was the same in LN229 cells. In xenograft mice model, tumor volume in Olaparib and Olaparib/shBRCA2 group was 376.12 and 84.95mm3 when tumor weight was 0.46 g and 0.12 g. In addition, the level of RAD51, RAD50, MRE11, and NBS was increased by Olaparib alone but decreased reversely after knockdown of BRCA2 in Daoy cells. CONCLUSIONS: Knockdown of BRCA2 increases the sensitivity of medulloblastoma cells to Olaparib and strengthens the efficacy of Olaparib in vitro and in vivo. Knockdown of BRCA2 causes DNA damage repair by regulating RAD51-mediated signaling pathway in Daoy cells.

Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population.

BACKGROUND: To describe the demographics, clinical characteristics and visual function of Asian patients with keratoconus managed in a tertiary eye centre. DESIGN: Prospective cross-sectional study. PARTICIPANTS: 116 patients with clinically evident or suspected keratoconus (on videokeratography) recruited over 11 months. METHODS: A standardised interview, full ophthalmic examination, refraction and corneal topography were performed. Visual function was assessed with the VF-14 questionnaire. MAIN OUTCOME MEASURES: Demographics, clinical characteristics and visual function. RESULTS: Mean age of our patients was 29.5 ± 9.40 years on enrolment, 62.9% were male, and the ethnic distribution was 60.3% Chinese, 13.8% Malays and 9.5% Indians. Clinically evident keratoconus was present bilaterally in 65 patients (56.0%) and unilateral keratoconus in five patients (4.3%). Five patients (4.3%) had a family history of keratoconus. The majority of patients were managed with contact lenses (60.8%) or glasses (24.5%). Eye rubbing was common (68%) as were asthma (26.3%) and eczema (18.4%). Conical protrusion was the commonest sign (75.3%). The mean cylinder was higher in keratoconus eyes compared with keratoconus suspect eyes (-4.01 vs. -1.27, P < 0.001), and best-corrected visual acuity was poorer (0.19 vs. 0.05, P < 0.001). Unaided visual acuity was significantly worse with increasing age (P = 0.016). On the VF-14, 32% scored 90 or less (out of 100), reflecting difficulties with vision-related daily activities. CONCLUSIONS: Our Asian patients with keratoconus had similar demographic and clinical characteristics to patients in Western populations. Even with apparently good visual acuity, some patients still experience substantial impairment in vision-related activities.

Substrate-induced covalent assembly of a chemzyme and crystallographic characterization of a chemzyme-substrate complex.

A substrate induced covalent assembly of a highly organized chemzyme known to be effective in both catalytic asymmetric aziridination and aza Diels-Alder reactions is described and the information gained from which led to an efficient one-pot aziridination protocol. The crystal structures of two chemzyme-iminium complexes were elucidated by X-ray diffraction analysis that provides critical insights into the binding of the substrates with the chemzyme.

Neuropsychiatric Symptoms and Risk Factors in Mild Cognitive Impairment: A Cohort Investigation of Elderly Patients.

BACKGROUND: Neuropsychiatric symptoms (NPS) have been shown to affect the progression and development of Alzheimer's disease (AD) in the elderly. However, the published data are still controversial and limited in large cohort-based NPS study. AIM: To explore the potential relationship between NPS and mild cognitive impairment (MCI) among the elderly of Chinese community. METHODS: A total of 465 Chinese community-dwelling elderly (age ≥ 60 years) with mild cognitive impairment (MCI) were recruited into this investigation. At baseline, enrolled participants were assessed for Clinical Dementia Rating (CDR), mini-psychiatric examination. They were also subjected to categorical language fluency test, list learning and delayed recall. We assessed the NPS severity by Neuropsychological Inventory (NPI). The global cognitive status (GCS) of the participants at the end of the 3-year study period were measured with the CDR. RESULTS: Approximately 41.6% of subjects had 1 or more NPS (total NPI score ≥ 1) at baseline. The most common NPSs were nocturnal behavior (20.8%), depression (17.3%), apathy (12.7%) and anxiety (13.2%). At the end of 3-year follow-up, 26.9% of baseline depressed patients developed AD, while 15.2% of baseline non-depressed patients developed AD (χ2 = 4.86, P=0. 04). Abnormal motor behavior was significantly correlated with cognitive deterioration as well (χ2 = 5.75, P=0. 03). Logistic regression analysis revealed that depression was considered as a risk factor for AD progression at baseline (95% CI: 1.12-5.67, OR=2.37, P=0.03). CONCLUSIONS: Depression may be an independent factor representing early neurodegeneration in elder patients with MCI. Further studies are warranted to assess whether effective management of NPS promotes the cognitive functions.

Evidence for a boroxinate based Brønsted acid derivative of VAPOL as the active catalyst in the catalytic asymmetric aziridination reaction.

Studies are described that were designed to determine the structure of the active catalyst in the asymmetric catalytic aziridination of imines with ethyl diazoacetate (AZ reaction). Evidence suggests that the active catalyst contains a boroxine ring in which one of the three boron atoms is spiro-fused with the two phenol groups of the VAPOL ligand. (11)B and (1)H NMR evidence supports the boroxinate structure B in which the counterion to the boroxinate is the protonated form of the imine. The boroxinate structure is also supported by two solid state structures of a VAPOL boroxinate in which the gegen cation is tetramethyl ammonium and 4-dimethylaminopyridinium.

Optically active calixarenes conduced by methylene substitution.

The first method for the synthesis of optically active calix[4]arenes that are chiral as a result of substitution on the methylene bridges is described. The key step in the synthesis involves the reaction of a biscarbene complex with a diyne, which generates two of the benzene rings and the macrocyclic ring of the calix in a single transformation. The utility of this triple annulation process is demonstrated in the synthesis of di- and tetramethoxycalix[4]arenes. The flexibility of this synthetic approach is demonstrated by the synthesis of two diastereomers of the tetramethoxycalix[4]arenes in which each is synthesized in a stereoselective fashion by proper control of the absolute configurations of the methoxy groups in the biscarbene complex and in the diyne.

Building blocks for molecule-based magnets: radical anions and dianions of substituted 3,6-dimethylenecyclohexane-1,2,4,5-tetrones as paramagnetic bridging ligands.

We have prepared four tetraaryl derivatives of 3,6-dimethylene-1,2,4,5-tetraoxocyclohexane (aryl = Ph; 4-MeOPh; 4-Me(2)NPh; and 3,5-(t-Bu)(2)-4-MeOPh) with guidance from an earlier reported ab initio analysis (Misiolek, A. W.; Jackson, J. E. J. Am. Chem. Soc. 2001, 123, 4774-4780). These electron acceptors may be chemically or electrochemically reduced to the mono- and dianions desired as building blocks for the assembly of molecule-based magnets. Cyclic voltammetry shows that the potential of the first reduction wave depends on the electron donor ability of the aryl ring substituents, ranging from -0.28 V for the tetraphenyl derivative to -0.78 V for the p-dimethylamino substituted analogue (vs ferrocene/ferrocinium(+) at 0.46 V). Spin density distributions in the semiquinone moieties were elucidated by electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) observations of hyperfine couplings to internal (1)H sites and bound alkali metal cations. X-ray diffraction studies of the sodium and potassium salts of the octa-t-butyltetramethoxy derivative reveal the structure of the monoanion and its tendency to self-assemble with metal cations into one-dimensional chains in the solid state. Within the chains the anions display the expected bridging and chelating mode of coordination; SQUID magnetometry revealed weak intermolecular spin-spin couplings of 2J = -0.2 and approximately 0 K for the sodium and potassium salts, respectively. NIR transitions in the electronic spectra of the monoanions in solution are consistent with the expected low energy gap between frontier orbitals and its tunability by substituent variations. EPR studies of the free dianions and monoradical analogues indicate diradical localization into separate triphenylmethyl-like monoradicals via twisting of the diarylmethylene termini.

Sirtuin 6 promotes cell aging of myeloma cell line KM-HM_(31) by via Hippo signal pathway.

OBJECTIVE: Myeloma poses a serious risk for people's health and life quality. Molecular targeted treatment of myeloma emerges as a promising therapy. This study aimed to determine the effect of Sirtuin 6 on myeloma KM-HM_(31) cell aging and provide evidence for clinical treatment. MATERIALS AND METHODS: Myeloma KM-HM_(31) cell aging model induced by Carbamide peroxide (CP) was generated. Cells were transfected with Sirtuin 6 over-expression plasmid and specific siRNA. Western blot was used to study Sirtuin 6 expression, P53, P16, and Hippo in KM-HM_(31) cells. ß-galactosidase assay was applied to measure cell aging. Verteporfin inhibited Hippo signal pathway and measured aging of KM-HM_(31) cells. RESULTS: The levels of Sirtuin 6, aging protein P53, and P16 were remarkably elevated while Hippo expression was significantly inhibited in CP-induced KM-HM_(31) cells. Transfection of Sirtuin 6 over-expression plasmid enhanced Sirtuin 6 expression in KM-HM_(31) cells and potentiated cell aging with downregulation of Hippo protein. In contrast, a block of Sirtuin 6 resulted in the opposite effect. Moreover, Verteporfin inhibited Hippo signal pathway and enhanced CP-induced KM-HM_(31) cell aging, which contributed similar effect as Sirtuin 6 did. CONCLUSIONS: We showed that sirtuin 6 facilitates CP-induced myeloma cell KM-HM_(31) aging via suppressing Hippo.

Circulating exosomal miRNAs as diagnostic biomarkers in Parkinson's disease.

OBJECTIVE: This research has showed that exosomal miRNAs from cerebrospinal fluid could act as biomarkers for Parkinson's disease (PD). However, no analysis has been conducted to explore the potential value of exosomal miRNAs from plasma. PATIENTS AND METHODS: 52 patients with PD were included in study group. 48 healthy adults were included in control group. Blood samples were collected from all those people and then exosomes were extracted from the plasma. RESULTS: Compared with controls, patients with PD showed a significantly higher expression of circulating exosomal miR-331-5p. ROC curve showed that the area values under the curve of miR-331-5p and miR-505 were 0.849 and 0.898, respectively. CONCLUSIONS: Exosomal miRNAs, including miR-331-5p and miR-505, could potentially act as biomarkers for PD.

In vivo response-based identification of direct hormone target cell populations using high-density tissue arrays.

To identify cell populations directly responsive to prolactin (PRL), GH, erythropoietin, or granulocyte-colony stimulating factor within the physiological setting of an intact mammal, we combined in situ detection of hormone-activated signal transducer and activator of transcription (Stat)-5 in rats with high-throughput tissue array analysis using cutting-edge matrix assembly (CEMA). Inducible activation of Stat5a/b, as judged by levels of nuclear-localized, phosphoTyr694/699-Stat5a/b, served as an immediate and sensitive in situ marker of receptor signaling in rat tissues after injection into male and female rats of a single, receptor-saturating dose of hormone for maximal receptor activation. CEMA tissue arrays facilitated analysis of most tissues, including architecturally complex, thin-walled, and stratified tissues such as gut and skin. In 40 tissues analyzed, 35 PRL-responsive and 32 GH-responsive cell types were detected, of which 22 cell types were responsive to both hormones. Interestingly, PRL but not GH activated Stat5 in nearly all of the endocrine glands. In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells. Finally, the organism-wide screening revealed a yet-to-be identified erythropoietin-responsive cell type in connective tissue. CEMA tissue arrays provide cost-effective in situ analysis of large numbers of tissues. Biomarker-based identification of cell populations responsive to individual hormones may shed new light on endocrine disease as well as improve understanding of effects and side effects of hormones and drugs.