The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies / 药物分析学报

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chlo-ride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl-extrusion,and sodium po-tassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl-loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable ad-vances in our understanding of CCCs'control mechanisms in cell volume regulations,with many tech-niques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptake-assay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring y-aminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride con-centration with sensitive microelectrodes,radiotracer 36Cl-,and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Na+uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review sum-marizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Value of lymph node regional sorting in radical colorectal cancer surgery / 中华普通外科杂志

Objective:To evaluate the value of lymph node regional sorting in radical colorectal cancer surgery.Methods:Between Jan 2021 and Mar 2022, A total of 307 colorectal cancer patients undergoing radical surgery at the Tianjin Medical University General Hospital were retrospectively included and assigned to either the lymph node regional sorting group (123) or no-sorting group (184) according to the lymph node examination methods.Results:There was a significant difference between the two groups in the number of total lymph nodes and negative lymph nodes (26.74±13.08 vs. 16.80±4.87, t=9.381, P<0.001; 25.65±13.25 vs. 16.04±4.87, t=8.979, P<0.001). The number of positive lymph nodes of lymph node regional sorting group increased compared with no-sorting group (1.09±2.28 vs. 0.76±1.34, t=1.589, P=0.113). A total of 52 cases in the lymph node regional sorting group showed metastasis, of which 10 showed lymph node skip metastases. There was no significant difference in tumor location and TNM stage between skip and non-skip lymph node metastasis patients. Conclusions:The lymph node regional sorting increase the number of examined lymph nodes. The method can determine the positive lymph node distribution and ensure the accuracy of staging.

Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a / 生物工程学报

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.

Molecular epidemiology of norovirus among infants with diarrhea in Chaoyang district, Beijing from 2011 to 2017 / 中华实验和临床病毒学杂志

Objective@#To investigate the genetic characteristics of human norovirus (NoV) among infants under 5 years of age with diarrhea in Chaoyang District, Beijing from 2011 to 2017.@*Methods@#NoV-positive stool samples were collected from 2011 to 2017 in this region. The partial RdRp and VP1 genes were amplified and sequenced. Multi-sequence alignment was performed and phylogenetic tree was constructed using Mega software.@*Results@#A total of 151 samples were sequenced and analyzed. The ratio of male and female was 2.28∶1 with mean age of 1.72 years. Fourteen NoV subtypes were detected, including GII.Pe/GII.4 (47.68%), GII.P12/GII.3 (20.53%), GII.P4/GII.4 (17.22%), GII.P16/GII.2 (3.31%), GII.P12/GII.12 (1.99%), GII.P17/GII.17 (1.99%), GII.P16/GII.13 (1.32%), GII.P7/GII.7 (1.32%), GII.P7/GII.6 (1.32%), GII.P2/GII.2 (0.66%), GII.P21/GII.21 (0.66%), GII.Pg/GII.12 (0.66%), GI.Pa/GI.3 (0.66%) and GI.P6/GI.6 (0.66%).@*Conclusions@#NoV genetic diversity was found among infants under 5 with diarrhea in Chaoyang district, Beijing. The subtypes from surveillance and those from epidemics occurred in chronological order. The surveillance should be strengthened for early detection of new subtype for monitoring the epidemic and vaccine design.

Molecular epidemiology of adenovirus infection among infants with diarrhea in Chaoyang district, Beijing from 2011 to 2017 / 中华实验和临床病毒学杂志

Objective@#To investigate the genetic characteristics of human adenovirus (AdV) among infants with diarrhea in Chaoyang district, Beijing from 2011 to 2017.@*Methods@#Adenovirus positive stool samples were collected from 2011 to 2017 in Chaoyang District of Beijing. The hexon region genes of human adenovirus were sequenced. Multi-sequence alignments were performed and phylogenetic tree was constructed by Mega software.@*Results@#A total of 64 samples were sequenced and analyzed. The ratio of male to female was 11∶5. The mean age was 1.56 years. Among them, AdV41 accounted for 70.31%, followed by AdV31 (26.25%), AdV40 (4.69%), AdV1 (3.13%), AdV5 (3.13%), AdV6 (3.13%), AdV7 (3.13%), AdV2 (1.56%), AdV3 (1.56%), AdV4 (1.56%) and AdV61 (1.56%).@*Conclusions@#Human adenovirus may play an important role in viral diarrhea in Chaoyang district from 2011 to 2017. The current adenovirus epidemic is complex and AdV41 was the dominant strain in this region.

Three-dimensional reconstruction and finite element analysis of the optic nerve head of a cat / 中国组织工程研究

BACKGROUND: Glaucoma is a kind of eye disease that can cause irreversible blindness which is characterized by visual field loss. Clinical research shows that the optic nerve head has changed before the visual field loss. The morphological changes of the optic nerve head have become the key to determine the early diagnosis of glaucoma and disease development. So it has important significance for us to study the morphological changes of the tissues of optic nerve head under the high intraocular pressure. OBJECTIVE: To establish three-dimensional finite element model of optic nerve head which includes choroid, retina and lamina cribrosa, and analyze the thickness of the optic nerve head under the acute high intraocular pressure. METHODS: (1) We chose healthy cats without refractive media and other eye diseases. The tomographic sequence images of the optic nerve head of a cat were obtained with the intraocular pressure of the normal value by using enhanced depth imaging spectral-domain optical coherence tomography. (2) The three-dimensional model of the retina, choroid and lamina cribrosa was obtained. Three-dimensional model of optic nerve head was established by assembling the model of the retina, the choroid and the lamina cribrosa. The thickness of the retina, choroid and lamina cribrosa was analyzed under different intraocular pressures by using the method of finite element analysis. (3) Animal model of acute ocular hypertension was established by methods of anterior chamber perfusion. The tomographic sequence images of the optic nerve head of a cat were obtained with different intraocular pressures by using enhanced depth imaging spectral-domain optical coherence tomography. Then, we measured the thickness changes of the choroid, retina and lamina cribrosa under different intraocular pressures, and compared with the results of finite element analysis. RESULTS AND CONCLUSION: The thickness of the choroid, retina and lamina cribrosa trended to be thin, and the cup dish ratio of optic nerve head increased gradual y with the increased intraocular pressures. Regarding to the thickness changes of the choroid, retina and lamina cribrosa, the trend of experimental measurement results was consistent with finite element calculation results. Hence, it is feasible to analyze morphological changes of every fundus tissue under high intraocular pressure using the tomographic sequence images obtained by optical coherence tomography. We can predict the morphological changes of the optic nerve head tissue by finite element analysis, which has certain guiding significance in determining the progression of glaucoma.