[Value of direct immunohistochemical staining in assisting intraoperative frozen diagnosis of bronchiolar adenoma].

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

High figure-of-merit in the heavy-fermion UN2 system for radioisotope thermoelectric applications.

The design of uranium-based thermoelectric (TE) materials presents a novel and intriguing strategy for directly converting nuclear heat into electrical power. Using high-level first-principles approach combined with accurate solution of Boltzmann transport equation, we demonstrate that a giant n-type power factor of 13.8 mW m-1 K-2 and a peak ZT value of 2.2 can be realized in the heavy-fermion UN2 compound at 700 K. Such promising TE performance arises from the large degeneracy (N v = 14) of heavy conduction band coupled with weak electron-phonon interactions, which is in principle governed by the strong Coulomb correlation among the partially filled U-5f electrons in the face-centered cubic structure. Collectively, our theoretical work suggests that the energetic UN2 could serve as both excellent heat source and efficient power convertor, which also uncovers an underexplored area for TE research.

Surprisingly good thermoelectric performance of a black phosphorus/blue phosphorus van der Waals heterostructure.

Thermoelectric properties of a black phosphorus/blue phosphorus van der Waals heterostructure are investigated by using first-principles calculations and Boltzmann transport theory for both electrons and phonons. It is found that the heterostructure is both energetically and kinetically stable even at higher temperature. Compared with those of the constituent black and blue phosphorus monolayers, the thermoelectric performance of the heterostructure is significantly enhanced due to sharply decreased thermal conductivity caused by the presence of van der Waals interactions, as well as obviously reduced band gaps and multi-valley structures resulting from type-II band alignment. As a consequence, the room temperature ZT value can reach 1.6, which is much higher than those of the components. Furthermore, we obtain ZT over 2.0 in a wide temperature range from 400 to 800 K, and a maximum ZT of ∼3.2 can be realized at 700 K, which is surprisingly good for systems consisting of light elements only.

High thermoelectric performance of half-Heusler compound BiBaK with intrinsically low lattice thermal conductivity.

Half-Heusler compounds usually exhibit relatively higher lattice thermal conductivity that is undesirable for thermoelectric applications. Here we demonstrate by first-principles calculations and Boltzmann transport theory that the BiBaK system is an exception, which has rather low thermal conductivity as evidenced by very small phonon group velocity and relaxation time. Detailed analysis indicates that the heavy Bi and Ba atoms form a cage-like structure, inside which the light K atom rattles with larger atomic displacement parameters. In combination with its good electronic transport properties, the BiBaK shows a maximum n-type ZT value of 1.9 at 900 K, which outperforms most half-Heusler thermoelectric materials.

Research Progress on Chiral Separation Methods and Toxic Effects of Methamphetamine Enantiomers.

ABSTRACT: Methamphetamine （MAMP） is a kind of amphetamine-type stimulants （ATS） which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-（+）-MAMP and R-（-）-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-（+）-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.

A comparative study of the thermoelectric performance of graphene-like BX (X = P, As, Sb) monolayers.

The electronic and phonon transport properties of graphene-like boron phosphide (BP), boron arsenide (BAs), and boron antimonide (BSb) monolayers are investigated using first-principles calculations combined with the Boltzmann theory. By considering both the phonon-phonon and electron-phonon scatterings, we demonstrate that the strong bond anharmonicity in the BAs and BSb monolayers can dramatically suppress the phonon relaxation time but hardly affect that of electron. As a consequence, both systems exhibit comparable power factors with that of the BP monolayer but much lower lattice thermal conductivities. Accordingly, a maximum ZT value above 3.0 can be realized in both BAs and BSb monolayers at optimized carrier concentration. Interestingly, very similar p - and n-type thermoelectric performance is observed in the BSb monolayer along the zigzag direction, which is of vital importance in the fabrication of thermoelectric modules with comparable efficiencies.

[Clinical features and genetics studies of Finnish variant late infantile neuronal ceroid lipofuscinosis in two families].

Objective: To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis. Methods: The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents. Results: The probands were 11 years and 3 moths, 9 years and 1 month,10 years and 1 month old. All were normal at birth, and from 5-6 years old they began to develop "regression of cognition and motion, impaired vision". Physical examination at the first consultation: clear minded butignorant, unable to speak and understand instructions, unable to stand up and sit alone, unable to maintain postureupright. The brain magnetic resonance imaging(MRI) indicated diffuse cerebral and cerebellar atrophy, white matter damage. Blood biochemistry, lactic acid, acid-base balancewere normal. Electron microscopic examination of peripheral blood lymphocytes showed swelling of the nucleus, autophagy, intracellular massive deposits and abnormal vacuoles. Two compound heterozygous c.334C> T (p.Arg112Cys) and c.595C> T (p.Arg199Ter) mutations of CLN5 gene were identified in the two siblings, and the proband 3 was c.335G> A (p.Arg199His) homozyousmutation, which were inherited from their unaffected parents. Conclusions: The 3 cases with Finnish variant late infantileneuronal ceroid lipofuscinosises were normal at birth, cognitive and motor function was regressed at preschool age.Brain MRI showed whole brain atrophy, white matter lesions, there were no bovious difference from other neurodegenerative diseases. Blood biochemistry and pathological examination of lymphocytes had no specific changes. The pathogenic genes were CLN5,most are inherited in autosomal recessive way.

TGF-ß induced epithelial-mesenchymal transition in an advanced cervical tumor model by 3D printing.

An advanced in vitro cervical tumor model was established by 3D printing to study the epithelial-to-mesenchymal transition (EMT), which is a very important stage of dissemination of carcinoma leading to metastatic tumors. A HeLa/hydrogel grid construct composed of gelatin, alginate, Matrigel and HeLa cells was fabricated by forced extrusion in a layer-by-layer fashion. HeLa cells rapidly proliferated, formed spheroids and presented tumorigenic characteristic in the 3D-printed structure. With the supplement of TGF-ß, aggregated HeLa cells started to disintegrate, and some of them changed into fibroblast-like spindle morphology, which indicated that EMT was induced. The down-regulation of epithelial marker E-cadherin, and up-regulation of mesenchymal markers such as snail, vimentin and N-cadherin were all observed in the 3D-printed model, and performed differently in 3D and 2D models. The TGF-ß induced EMT was inhibited by the treatment of disulfiram and EMT pathway inhibitor C19 in a dose dependent manner, showing great potential for future studies of a therapeutic program towards cervical tumor metastasis.

Clinical effects and safety review of self-expanding stent surgery for extracranial carotid artery stenosis treatment.

This study aimed to investigate the clinical effects and safety review of self-expanding stent surgery in the treatment of extracranial carotid artery stenosis. Seventy-eight patients with carotid artery stenosis were applied with the self-expanding stent for endovascular interventional therapy. Eighty-one stents were implanted into 80 blood vessels of the 78 patients, in which protective umbrellas were used in 56 cases, and the success rate of stent implantation was 100%. The stenosis degree decreased from the preoperative (86.72 ± 9.5%) to the postoperative (13.43 ± 5.62%) stage, and the blood peak velocity of the stenosed vessels decreased from 189.58 ± 13.5 to 83.73 ± 5.61 cm/s. Transient blood pressure and heart rate decreases occurred in 21 cases, continuously low blood pressure and heart rate decreasing occurred in 29 cases, and acute occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was resolved through thrombolysis and thrombus breaking in time. Over-perfusion symptoms were observed in 13 cases, although without serious complications such as cerebral hemorrhage. The follow-up period continued for 6-32 months, and ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had restenosis. The application of self-expanding stents had good clinical effects, with fewer complications and higher safety for the treatment of extracranial carotid artery stenosis.

Efficacy of treatment with antisense oligonucleotides complementary to immunoglobulin sequences of bcl-2/immunoglobulin fusion transcript in a t(14;18) human lymphoma-scid mouse model.

In t(14;18)-positive lymphoma cells, bcl-2 is expressed from a fusion mRNA transcript containing the full coding sequence of bcl-2 and 3' immunoglobulin sequences. We reported previously that antisense oligodeoxyribonucleotides directed at the bcl-2 translational start site, as well as those targeted to immunoglobulin sequences 3' of the translocation breakpoint, down-regulate bcl-2 and inhibit growth of the t(14;18)-positive lymphoma line WSU-FSCCL in vitro. We have developed a scid mouse model with this human cell line and demonstrate that antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences down-regulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells in vivo. This leads to prolonged survival of the mice. Targeting non-oncogenic sequences outside of the breakpoints of fusion transcripts may be a clinically useful therapeutic strategy.

Expression of transforming growth factor-beta 1 in prostate cancer.

Transforming growth factor-beta 1 (TGF beta 1) is a potent modulator of cell proliferation, differentiation, angiogenesis, and the immune system. TGF beta 1 messenger RNA (mRNA) levels were much higher in several rat prostate adenocarcinomas (Dunning R3327 MATLyLu, AT2, G, HI, and H sublines) than in normal prostate. Normal prostate and the well differentiated H and HI tumors produced two TGF beta 1 mRNA transcripts, 2.4 kilobases (major) and 1.6 kilobases (minor). The poorly differentiated MATLyLu and AT2 sublines produced these plus additional TGF beta 1 mRNA transcripts that were present in the primary tumors, metastases, and cultured cell lines. TGF beta 1 mRNA levels were unchanged 2 weeks after castration. Immunohistochemical staining of TGF beta 1 protein was more prominent and more extensive in prostate cancer than in normal prostate. Only extracellular TGF beta 1 staining was detected. In normal prostate and in well differentiated tumors (H and HI), extracellular TGF beta 1 staining was located in the interacinar stroma, suggesting that it may be produced there. In contrast, in the poorly differentiated tumors (MATLyLu, AT2, and G) that contain sheets of epithelial cells, extracellular TGF beta 1 staining was present throughout the tumor, suggesting that TGF beta 1 may be made and secreted by the tumor epithelial cells. MATLyLu, AT2, and G tumor cells were cultured in vitro, and the conditioned medium was analyzed for the presence of TGF beta using a bioassay. TGF beta 1 is produced and secreted as an inactive latent precursor and must be activated to release bioactive TGF beta 1. Cells secreted about 100-500 pg TGF beta/10(6) cells.24 h and were able to activate about 50% of the total TGF beta secreted. Because TGF beta 1 mRNA and protein expression are higher in cancerous than normal tissue and because prostate cancer cells themselves can activate latent TGF beta 1 to a bioactive form, TGF beta 1 produced endogenously by prostate cancer has the potential to affect tumor behavior in vivo. Therefore, TGF beta 1 may represent a new therapeutic target in prostate cancer.

Involvement of central vs. peripheral mechanisms in mediating sympathoadrenal activation in endotoxic rats.

The contribution of central vs. peripheral mechanisms in mediating increases in plasma norepinephrine (NE) and epinephrine (Epi) during endotoxicosis were studied. Plasma catecholamine responses after endotoxin were assessed in conscious animals and in animals without central regulatory mechanisms (pithed rats). In conscious rats, endotoxin (1.5 mg/kg i.v.) induced a marked elevation in plasma NE after 90 min (3-fold), but elevations were not seen in pithed rats. Endotoxin also induced a profound increase (12- to 13-fold) in plasma Epi in conscious rats, but increases were less (2- to 3-fold) and delayed in pithed rats. These results suggest that central mechanisms are essential in plasma NE response to endotoxic challenge, whereas plasma Epi response involves both central and peripheral mechanisms, with the former being dominant. In conscious adrenal-denervated animals, plasma Epi was not elevated until 90 min postendotoxin. This delayed Epi elevation was approximately one-third of the maximal response observed in conscious adrenal-intact rats. In pithed adrenal-denervated rats, plasma Epi at 90 min postendotoxin was also increased to a level comparable to that in pithed adrenal-intact rats. These results imply that a significant fraction of peripheral release of Epi with endotoxicosis is nonneurogenic.

Arterial baroreflexes are not essential in mediating sympathoadrenal activation in conscious endotoxic rats.

We examined the contributions of arterial baroreceptor reflexes in mediating sympathoadrenal activation during endotoxicosis. Conscious rats with chronic sinoaortic denervation (SAD) or sham-operation (SHAM) were subject to endotoxin treatment (5 mg/kg, i.v.). Hemodynamic responses, renal sympathetic nerve activity (RSNA) and plasma catecholamines were assessed at different times post endotoxin infusion. In both SAD and sham groups, intravenous endotoxin injection induced a rapid and significant sympathoadrenal activation, as indicated by a parallel elevation of RSNA and plasma catecholamines. Such activation peaked 15-30 min following endotoxin and was sustained throughout the 2-3 h protocol. The early response of the sympathoadrenal system to endotoxin is more profound in SAD rats compared to sham rats. We propose that the afferent neural input from arterial baroreceptors is not essential in mediating sympathoadrenal activation during sepsis. The elimination of feedback buffering mechanisms with SAD may account for the augmented sympathetic response seen in SAD animals.

Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats.

Conscious rats treated with bolus endotoxin (ET; 4.0 mg/kg) increased plasma epinephrine (Epi) 48-fold (from 134 +/- 5 to 6,545 +/- 1,607 pg/ml) at 30 min, but by 6 h this elevation was less than 9-fold above control (1,174 +/- 166 pg/ml). In contrast, plasma norepinephrine (NE) elevation (6.5-fold above control) was maintained during the protocol. The present study was designed to test the hypothesis that the decreased Epi response following ET was due to 1) depletion of adrenal Epi content such that adrenomedullary stimulation would not release Epi, 2) decreased Epi release with direct stimulation, i.e., desensitization of release, or 3) decreased afferent signals generated by ET itself. In these experiments an initial low ET dose (0.5 mg/kg) was followed 3 h later by a second dose of either the same (0.5 mg/kg) or greater (4.0 mg/kg) magnitude. Plasma Epi was elevated following the initial (low) dose but not following the same second (0.5 mg/kg) dose, whereas the second higher dose (4.0 mg/kg) resulted in elevated plasma Epi. This response to high dose was 60% less than that observed with 4.0 mg/kg as an initial dose. Just before the second ET bolus, there was no depletion of adrenal Epi content (P greater than 0.05 saline vs. ET treated), and direct nerve stimulation demonstrated enhanced rather than attenuated Epi release from the adrenal medulla (P less than 0.05 saline vs. ET treated). These results suggest that the decline in Epi following the ET-induced elevation may be mediated by a decrease in the afferent signal that initiates Epi release.

Sympathoadrenal activation in sinoaortic-denervated rats following endotoxin.

We evaluated the role of the baroreceptor reflex in mediating the sympathoadrenal activation during endotoxicosis, using acutely as well as chronically denervated rats. Three groups of experiments were conducted. In the first experiment, hemodynamic and plasma catecholamine responses following endotoxin (5 mg/kg iv) were measured in alpha-chloralose-anesthetized rats with acute sinoaortic baroreceptor denervation (SAD) or sham operation. In the second experiment, chronically sinoaortic-denervated rats and sham controls were used and experiments were conducted as in acute preparations. In the third experiment hydralazine (1 mg/kg iv) was given to chronically denervated rats and sham controls to evaluate the singular contribution of hypotension-evoked baroreflex disinhibition in the absence of endotoxin. In both acute and chronic preparations, endotoxin induced marked elevation of plasma norepinephrine and epinephrine in the presence as well as the absence of arterial baroreceptors (P greater than 0.05). Plasma catecholamines were significantly increased by hydralazine-induced hypotension in the sham group, but this elevation was far less than that induced by endotoxin. Hypotension alone did not significantly increase plasma catecholamines in SAD rats. These results suggest that the baroreflex is not the major factor in mediating sympathoadrenal activation during endotoxicosis and that non-baroreflex mechanisms may be involved in stimulating such activation.

The vascular response to adrenergic stimulation in pithed rats following endotoxin.

In vivo and in vitro studies have shown that the vascular response to catecholamine is attenuated during endotoxemia. The mechanism of such attenuation is complex and might involve high catecholamine-induced desensitization of adrenoceptors. The purpose of this study was to assess the vascular response to adrenergic stimulation after endotoxin (ETX) administration in pithed rats. In pithed rats, sympathetic outflow is controlled by stimulation, ETX does not elevate norepinephrine (NE), and there are no compensatory reflexes. Rats were pithed, curarized, and adrenal-demedullated. Preganglionic thoracolumbar nerves were stimulated (3 Hz, 10 V, 0.5 msec) for 1 hr after pithing, at which time the first set of frequency and NE-dose responses were assessed by measuring the peak increase in diastolic blood pressure. Intravenous ETX (1.5 mg/kg or 0.5 mg/kg) or saline was administered immediately after these measurements. A sham group was designed to mimic the falling blood pressure pattern seen in the endotoxin group during 1 hr after ETX was given by gradually decreasing the stimulation frequency. The second set of frequency and NE-dose responses were evaluated 1 hr after ETX, saline, or sham treatment. Plasma NE and epinephrine (EPI) were determined before and 1 hr after ETX (1.5 mg/kg) or saline injection. The results showed that blood pressure response to adrenergic stimulation was markedly attenuated in pithed rats following both high and low doses of ETX compared with the saline and sham groups. Plasma NE was not elevated by ETX insult in pithed rats. We propose that mechanisms other than high-catecholamine-induced adrenergic desensitization or hypotension account for the attenuated adrenergic responsiveness of the vasculature following ETX.

Diagnosis of interstitial cystitis.

We reviewed clinical and histological findings in 55 patients with interstitial cystitis and 21 with voiding dysfunction secondary to other pathological conditions. Of our interstitial cystitis patients 36% would fail to meet the research definition proposed at a recent National Institutes of Health workshop. Detrusor mastocytosis was present in 64% of our interstitial cystitis patients compared to 80% of the noninterstitial cystitis group. There was no statistically significant difference in mean detrusor mast cell counts between interstitial cystitis and noninterstitial cystitis patients. Biopsies of 12 patients who did meet the proposed National Institutes of Health research definition were evaluated by immunohistochemical techniques. Early results are inconclusive. These studies indicate that interstitial cystitis is a complex disease whose diagnosis presently still must be made from a symptom complex rather than from objective histological criteria, including mastocytosis or the presence of any specific immunoreactive cell.