Frontiers in liver transplantation for liver cancer: sarcopenia / 中华器官移植杂志

Liver cancer patients scheduled for liver transplantation (LT) are frequently accompanied by liver cirrhosis.Within a state of long-term malnutrition and inflammatory stress, they are prone to sarcopenia with a poor efficacy of LT.Influenced by such multiple factors as surgery, infections and metabolic disorders, there is an elevated risk of exacerbation or a new onset of sarcopenia after LT.Therefore meticulous managements of sarcopenia are required throughout all aspects and periods of LT.A refined recipient stratification system of sarcopenia can accurately predict the efficacy of LT and its evaluating system has been becoming more precise, diverse and intelligent.Currently basic researches of sarcopenia have remained in infancy and its interactions with the related organs have become a novel research field.Sarcopenia has become an emerging challenge of LT for liver cancer.Further mechanistic explorations of sarcopenia are warranted and clinical precision managements should be further optimized.

Clinical characteristics of patients with colon complications after necrotizing pancreatitis: a retrospective cohort study / 中华外科杂志

Objective: To investigate the clinical characteristics of colon complications in patients with necrotizing pancreatitis(NP). Methods: The clinical data of 403 patients with NP admitted to the Department of General Surgery,Xuanwu Hospital, Capital Medical University from January 2014 to December 2021 were retrospectively analyzed. There were 273 males and 130 females,aged (49.4±15.4) years(range: 18 to 90 years). Among them,there were 199 cases of biliary pancreatitis,110 cases of hyperlipidemic pancreatitis,and 94 cases of pancreatitis caused by other causes. A multidisciplinary diagnosis and treatment model was used to diagnose and treat patients. Depending on whether the patients had colon complications,they were divided into colon complications group and noncolon complications group. Patients with colon complications were treated with anti-infection therapy,parental nutritional support,keeping the drainage tube unobstructed,and terminal ileostomy. The clinical results of the two groups were compared and analyzed using a 1∶1 propensity score match(PSM) method. The t test,χ2 test, or rank-sum test was used to analyze data between groups,respectively. Results: The incidence of colon complications was 13.2%(53/403),including 15 cases of colon obstruction,23 cases of colon fistula,and 21 cases of colon hemorrhage. After PSM,the baseline and clinical characteristics at admission of the two groups of patients were comparable (all P>0.05). In terms of clinical outcome,compared to patients with NP without colon complications,the number of patients with colon complications who received minimally invasive intervention(88.7%(47/53) vs. 69.8%(37/53),χ2=5.736,P=0.030),the number of minimally invasive interventions (M(IQR))(2(2) vs. 1(1), Z=4.638,P=0.034),the number of patients with multiple organ failure(45.3%(24/53) vs. 32.1%(17/53),χ2=4.826,P=0.041),and the number of extrapancreatic infections(79.2%(42/53) vs. 60.4%(32/53),χ2=4.476,P=0.034) increased significantly. The time required for enteral nutrition support(8(30)days vs. 2(10) days, Z=-3.048, P=0.002), parental nutritional support(32(37)days vs. 17(19)days, Z=-2.592, P=0.009),the length of stay in the ICU(24(51)days vs. 18(31)days, Z=-2.268, P=0.002),and the total length of stay (43(52)days vs. 30(40)days, Z=-2.589, P=0.013) were also significantly prolonged. However,mortality rates in the two groups were similar(37.7%(20/53) vs. 34.0%(18/53),χ2=0.164,P=0.840). Conclusions: Colonic complications in NP patients are not rare,which can lead to prolonged hospitalization and increased surgical intervention. Active surgical intervention can help improve the prognosis of these patients.

Fibroblast growth factor 21 (FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB (TFEB)-regulated lipophagy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).

Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

Inhibitory effect of CLC-2 chloride channel targeted blocking on fibrosis of human conjunctival fibroblasts / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of CLC-2 chloride channel targeted blocking on fibrosis of human conjunctival fibroblasts (HConF).Methods:HConF were divided into blank control group, lipofectamine 2000 (Lipo2000) group, nonsense small interfering RNA (siRNA) group, and CLC-2 siRNA transfected group.The HConF were cultured in medium containing the corresponding transfection reagents according to grouping.No intervention was given to blank control group.The expression level of CLC-2 mRNA of HConF was detected by real-time fluorescence quantitative PCR; absorbance ( A) value indicating the proliferative ability of HConF was determined by CCK-8 kit; the apoptosis ratio of HConF was tested by flow cytometry; the migration ability of HConF was identified by cell scratch test and Transwell migration assay; the contraction rate of HConF was assayed by collagen contraction test; the expression levels of collagenⅠ, collagen Ⅲ, PI3K, Akt, p-PI3K and p-Akt proteins were measured by Western blot. Results:Significant differences were found in relative expression levels of CLC-2 mRNA and A value among four groups ( F=90.110, 198.680; both at P<0.001). The relative expression level of CLC-2 mRNA and A value were significantly lower in CLC-2 siRNA transfected group than nonsense siRNA group, showing statistically significant differences (both at P<0.001). The proportion of apoptotic HConF in blank control group, Lipo2000 group, nonsense siRNA group, and CLC-2 siRNA transfected group was (4.78±1.10)%, (4.54±1.51)%, (4.82±0.88)% and (28.90±0.91)%, respectively, and a statistically significant difference was found ( F=363.260, P<0.001). The proportion of apoptotic HConF was significantly higher in CLC-2 siRNA transfected group than nonsense siRNA group, with a statistically significant difference ( P<0.001). Statistically significant differences were found in cell migration rate and the number of migrating cells among four groups ( F=74.493, 1 625.431; both at P<0.01). The cell migration rate of HConF in CLC-2 siRNA transfected group was significantly lower and the number of migrating cells was significantly smaller than those of nonsense siRNA group, with statistically significant differences (both at P<0.001). A statistically significant difference in contraction rate was found among four groups ( F=104.692, P<0.001). The contraction rate of HConF was significantly lower in CLC-2 siRNA transfected group than nonsense siRNA group, and the difference was statistically significant ( P<0.001). Statistically significant differences were found in relative expression levels of collagen Ⅰ and collagen Ⅲ proteins, p-PI3K/PI3K ratio, and p-Akt/Akt ratio among four groups ( F=112.073, 456.931, 340.889, 43.021; all at P<0.001). The relative expression levels of collagen Ⅰ and collagen Ⅲ proteins, p-PI3K/PI3K ratio and p-Akt/Akt ratio in CLC-2 siRNA transfected group were significantly lower than those of nonsense siRNA group, showing statistically significant differences (all at P<0.05). Conclusions:Targeted blocking of CLC-2 chloride channel gene expression can inhibit fibrosis of HConF by promoting apoptosis of HConF through PI3K/Akt signaling pathway and inhibit fibrotic processes such as cell migration, collagen synthesis and collagen contraction.

Therapeutic effect of liraglutide on non-alcoholic fatty liver disease rats and its influence on the expression of FGF21 / 中国医师杂志

Objective:To study the therapeutic effect of liraglutide on rat models with non-alcoholic fatty liver disease (NAFLD) and its influence on the expression of fibroblast growth factor 21 (FGF21).Methods:Thirty five Sprague Dawley (SD) rats were randomly divided into normal control group (15 rats) and control group (20 rats). They were fed with normal diet and high fat diet respectively. The NAFLD rat model was established by feeding the model group for 12 weeks. After successful modeling, the model group was randomly divided into liraglutide group and model group. 600 μg/(kg·d) liraglutide and equal volume normal saline were injected intraperitoneally respectively. All rats were killed at the 16th week. Serum FGF21, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (TC) were measured; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of rat liver tissue, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of FGF21 mRNA in rat liver tissue.Results:The liver index and serum ALT, AST, TC and TG contents in model group were significantly higher than those in normal control group (all P<0.05). The above indexes in liraglutide group were significantly lower than those in model group (all P<0.05). There was no significant difference in serum FBG level among the three groups ( P>0.05). HE staining showed that there were no abnormal pathological changes in liver of normal control group. Steatosis and inflammatory cell infiltration occurred in liver cells of model group. Compared with model group, liver steatosis and inflammatory cell infiltration in liraglutide group were significantly reduced. The level of FGF21 in serum and mRNA expression of FGF21 in liver tissue in model group were significantly higher than those in normal control group ( P<0.05). The levels of FGF21 in serum and FGF21 mRNA in liver tissue in liraglutide group were lower than those in model group ( P<0.05). Conclusions:Liraglutide can effectively delay the development of NAFLD in rats, and its mechanism may be related to the regulation of the expression of FGF21.

Historical Evolution and Modern Clinical Application of Shengyang Yiweitang / 中国实验方剂学杂志

Shengyang Yiweitang is one of the first 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine. It originated from the Clarifying Doubts about Damage from Internal and External Causes by physician LI Dongyuan of Jin dynasty， and is composed of Astragali Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Pinelliae Rhizoma， Citri Reticulatae Pericarpium， Angelicae Pubescentis Radix， Saposhnikoviae Radix， Notopterygii Rhizoma et Radix， Bupleuri Radix， Paeoniae Radix Alba， Alismatis Rhizoma， and Coptidis Rhizoma. With the effects of replenishing Qi， promoting Yang， clearing heat and removing dampness， Shengyang Yiweitang is used to treat spleen-stomach weakness and dampness-heat accumulation syndrome. Using bibliometrics， the authors systematically sorted out the source，composition， dosage， preparation， efficacy， indications， principle of composition， origin and processing of drugs，and modern clinical application of the prescription， and explored its history and key information. Additionally， it was found that Shengyang Yiweitang was widely used in modern clinical practice and was suitable for multisystem diseases， of which digestive system （264） was the most common， accounting for 41.71%， followed by urogenital system （57， 9.00%） and nervous system （48， 7.58%）. Although the treatment scope was wide， the pathogenesis of the diseases in traditional Chinese medicine belongs to "spleen-stomach weakness"， which fully reflected Li's academic thought of "internal injury of spleen and stomach leads to various diseases". The key information of Shengyang Yiweitang was determined by summarizing the relevant ancient books and modern literature， so as to provide accurate reference for its rational clinical application and further research and development.

Historical Evolution and Modern Clinical Application of Shengyang Yiweitang / 中国实验方剂学杂志

Shengyang Yiweitang is one of the first 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine. It originated from the Clarifying Doubts about Damage from Internal and External Causes by physician LI Dongyuan of Jin dynasty， and is composed of Astragali Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Pinelliae Rhizoma， Citri Reticulatae Pericarpium， Angelicae Pubescentis Radix， Saposhnikoviae Radix， Notopterygii Rhizoma et Radix， Bupleuri Radix， Paeoniae Radix Alba， Alismatis Rhizoma， and Coptidis Rhizoma. With the effects of replenishing Qi， promoting Yang， clearing heat and removing dampness， Shengyang Yiweitang is used to treat spleen-stomach weakness and dampness-heat accumulation syndrome. Using bibliometrics， the authors systematically sorted out the source，composition， dosage， preparation， efficacy， indications， principle of composition， origin and processing of drugs，and modern clinical application of the prescription， and explored its history and key information. Additionally， it was found that Shengyang Yiweitang was widely used in modern clinical practice and was suitable for multisystem diseases， of which digestive system （264） was the most common， accounting for 41.71%， followed by urogenital system （57， 9.00%） and nervous system （48， 7.58%）. Although the treatment scope was wide， the pathogenesis of the diseases in traditional Chinese medicine belongs to "spleen-stomach weakness"， which fully reflected Li's academic thought of "internal injury of spleen and stomach leads to various diseases". The key information of Shengyang Yiweitang was determined by summarizing the relevant ancient books and modern literature， so as to provide accurate reference for its rational clinical application and further research and development.

Changes of pancreatic gene expression and signal transduction pathway in large conductance calcium-activated potassium channels gene knockout rats detected by transcriptome sequencing / 中华胰腺病杂志

Objective:To investigate the differences of gene expression and signal transduction pathways in large conductance calcium-activated potassium channels(BKCa) gene knockout rats and analyze the role of BKCa gene in pancreas.Methods:Three adult female BKCa knockout SD rats (BKCa knockout group) were donated by Professor Wang Wei from Department of Pathology and Physiology of Basic Medical College of Capital Medical University, and three wild type adult femal SD rats were used as wide-type group. The whole pancreas was resected and RNA was extracted. RNA transcriptome sequencing (RNA-seq) technology was used for sequencing and DESeq2 differentiation analysis software was used for screening differentially expressed genes between two groups, and the gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed. The key genes were validated by RT-PCR.Results:18 258 genes were detected by sequencing in the 2 groups. There were statistically significant differences in the expression of 348 genes screened by DESeq2, 200 of which were highly expressed in the pancreas of BKCa knockout group, and 148 of which were low-expressed. 214 differentially expressed genes enrichments were found in GO database, including 25 involved in biological process, 18 in cell components and 14 molecular functions. All 348 differentially expressed genes were found in KEGG database, 15 of which were significantly enriched in PI3K/Akt signaling pathways. RT-PCR results showed that the expression of key genes Hsp90ab1, Hsp90aa1, Foxo3a and Col1a2 in the BKCa knockout group was significantly higher than that in wide type group ( P<0.0001), while Thbs1, Pik3r1 and Ppp genes were not significantly different. Conclusions:Differentially expressed genes and related important regulatory signaling pathways were screened out between BKCa knockout SD rats and wild-type SD rats at the transcriptional level, and PI3K/Akt pathway was found to be the most enriched, providing an important clue for predicting the function of BKCa in the pancreas.

Dual role of interleukin-33 in tumors / 中南大学学报(医学版)

Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.

Sarcopenia: a new challenge in liver transplantation / 中华消化外科杂志

Liver transplantation remains as the first choice treatment for patients with end stage liver diseases. Sarcopenia is a skeletal muscle disease characterized by loss of muscle mass and muscle function. As a common but easily overlooked complication, sarcopenia significantly influences the death and prognosis of recipients with cirrhosis and liver cancer waiting liver trans-plantation, which significantly influences the death and prognosis of those patients. Scientific evalua-tion and fine stratification of sarcopenia are expected to achieve precision intervention and improve prognosis of liver transplantation recipients.As sarcopenia is increasingly important in perioperative as well as medium and long-term management of liver transplantation recipients, it should be incorporated into normalized clinical diagnosis and treatment system. The authors review the research results at home and abroad, and comprehensively expound the research progress of sarcopenia in liver transplantation, in order to improve the cognition of sarcopenia in liver transplan-tation recipients in China.

Discrimination of lung cancer and adjacent normal tissues based on permittivity by optimized probabilistic neural network / 南方医科大学学报

OBJECTIVE@#To propose a probabilistic neural network classification method optimized by simulated annealing algorithm (SA-PNN) to discriminate lung cancer and adjacent normal tissues based on permittivity.@*METHODS@#The permittivity of lung tumors and the adjacent normal tissues was measured by an open-ended coaxial probe, and the statistical dependency (SD) algorithm was used for frequency screening.The permittivity associated with the selected frequency points was taken as the characteristic variable, and SA-PNN was used to discriminate lung cancer and the adjacent normal tissues.@*RESULTS@#Three frequency points, namely 984 MHz, 2724 MHz and 2723 MHz, were selected by SD algorithm.SA-PNN was used to discriminate 200 samples with the permittivity at the 3 frequency points as the characteristic variable.After 10-fold cross-validation, the final discrimination accuracy was 92.50%, the sensitivity was 90.65%, and the specificity was 94.62%.@*CONCLUSIONS@#Compared with the traditional probabilistic neural network, BP neural network, RBF neural network and the classification discriminant analysis function (Classify) in MATLAB, the proposed SA-PNN has higher accuracy, sensitivity and specificity for discriminating lung cancer and the adjacent normal tissues based on permittivity.

Selection and optimization of nutritional risk screening tools for esophageal cancer patients in China

Purification and characterization of two PR-10 protein isoforms from the crude drug of Angelica sinensis / 生物工程学报

Two proteins of similar molecular weight (named as ASPR-C-1 and ASPR-C-2) from the crude drug of Angelica sinensis were purified and characterized by 80% ammonium sulfate precipitation, Sephadex G-50 gel filtration chromatography, and DEAE-Sepharose anion exchange chromatography. The molecular weight of ASPR-C-1 and ASPR-C-2 on SDS-PAGE was 17.33 kDa and 17.18 kDa, respectively. They were mainly monomeric in solution, but partially formed dimers and they were glycoproteins with glycosyl content of 2.6% and 8.2%, respectively. Both ASPR-C-1 and ASPR-C-2 were identified to be members of pathogenesis-related 10 family of proteins by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and have ribonuclease activities with the specific activity of 73.60 U/mg and 146.76 U/mg, respectively. The optimum pH of the two isoforms was similar, at about 5.6, while their optimum temperatures were different. The optimum temperature of ASPR-C-1 was 50 ℃, and that of ASPR-C-2 was 60 ℃. Both isoforms presented highest thermal stability at 60 ℃. However, ASPR-C-2 was more thermotolerant than ASPR-C-1. The latter was rapidly inactivated and retained only about 20% residual activity while the former still maintained about 80% of its original activity at a higher treatment temperature (80 to 100 ℃). In addition, Fe²⁺ had an activating effect on the ribonuclease activities of two isoforms while Ca²⁺, Mg²⁺, Zn²⁺, Mn²⁺, Ag⁺, Cu²⁺, EDTA (Elhylene diamine tetraacetic acid), dithiothreitol and sodium dodecylsulphate showed different degrees of inhibition of the enzyme activities. Our findings provide a foundation for further research on the biological function of PR-10 protein from Angelica sinensis.

Current Situation and Demand Analysis of Rehabilitation Personnel by Stratified Sampling / 中国康复理论与实践

Objective:To explore the problems and give reasonable advice by investigating the current situation and needs of rehabilitation professionals nationwide. Methods:This research investigated the rehabilitation institutions invested by Disabled Persons' Federation system, sanitary system, privately-run institutions and People's Insurance Company from March to July, 2015 to collect data of rehabilitation physicians and therapists, in which the questionnaire survey, expert consultation and on-spot investigation were used. Results:The survey issued 416 questionnaires, 329 questionnaires were recalled, and 261 out of them were eligible. The profession titles of rehabilitation professionals were generally low, 39.3% were below the primary profession title; rehabilitation professionals were lack of educational background, 34.2% were college degree or below; low salary lead to low competence to other industries, 66.4% employees were paid 2000 to 4000 Yuan (RMB) per month; rehabilitation institutions were most in need of rehabilitative physicians, speech therapists and psychotherapists; lack of professionals, lack of bonus and space limitation ranked the top three of the restrictive factors. Conclusion:At present, the contradiction that the quantity and quality of rehabilitation talents cannot meet the increasing demand of rehabilitation is becoming more and more prominent. To solve the root of the problem, we need to start with the cultivation of talents, and the government needs to give policy support, open green pass and give strong assistance in cultivation of talents, academic title evaluation, salary levels, and policy guarantee system of rehabilitation to promote the rapid, sustaining and healthy development of rehabilitation industry.

The effect and mechanisms of chloride channel blocker NPPB on TGF-β1 induced HConF fibrosis / 中华实验眼科杂志

Objective To study the effect and mechanisms of chloride channel blocker 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) on thansforming growth factor β1 (TGF-β1) induced human conjunctival fibroblasts (HConF) fibrosis.Methods Cell counting kit (CCK-8) was used to screen out the optimal TGF-β1 treatment time and the optimal NPPB concentration.The cells were divided into control group,TGF-β1 treatment group and TGF-β1+NPPB group.Cell proliferation and cell cycle were detected by CCK-8 and flow cytometer,respectively.Cell migration ability were observed by scratch and transwell migration assays.Western blot and Real time-PCR were used to detect the expression of collagen Ⅰ (COL-Ⅰ),fibronectin (FN) and α-smooth muscle actin (α-SMA).The phosphorylation level of PI3K and Akt were measured by Western blot.Results TGF-β1 promotes cell proliferation in a time-dependent manner.There was no statistically significant difference in A values between 48 hours and 72 hours after TGF-β1 treatment (P =0.064).Forty-eight hours was selected as the most appropriate time for TGF-β1 treatment.NPPB inhibited HConF cell proliferation in a concentration-dependent manner.Compared with the control group,the proliferation A values of cells in the 50 mol/L and 100 mol/L NPPB groups were significantly reduced (P =0.020,0.000),and 100 mol/L was selected as the optimal concentration of NPPB.The cell proliferation A value,migration area and migration cell number of TGF-β1 +NPPB group were significantly lower than those of TGF-β1 treatment group (all at P＜0.05).Compared with the control group and TGF-β1 +NPPB group,the proportion of G1 phase cells in the TGF-β1 treatment group was reduced,and the proportion of cells in the S phase and G2/M phase were increased,with statistically significant differences between them (all at P ＜ 0.05).The protein and mRNA expression of α-SMA,COL-Ⅰ and FN in the TGF-β1 treatment group were higher than those in the control group and TGF-β1+NPPB group,with statistically significant differences between them(all at P＜0.05);the ratios of p-PI3K/PI3K and p-Akt/Akt in the TGF-β1 treatment group were significantly higher than those in the control group and TGF-β1 +NPPB group,with statistically significant differences between them (all at P＜0.05).Conclusions NPPB may inhibit TGF-β1 induced HConF fibrosis process by inhibiting phosphorylation of PI3K and Akt.

Osteogenic potential of different adipose derived stem cells in rats / 中华口腔医学杂志

Objective@#To compare the in vitro osteogenic ability of brown adipose stem cells (BADSC) and white adipose stem cells (WADSC), and to provide evidence for further research and clinical application of adipose-derived stem cells.@*Methods@#The brown fat under the scapula of SD rats and the white adipose tissue in the groin were isolated and obtained BADSC and WADSC. The morphology of the cells was observed by an inverted phase contrast microscope, and the cell count was used to detect the proliferative ability. After osteogenic induction, alkaline phosphatase (ALP) staining and alizarin red staining were performed. The expression of the osteogenic marker gene [Runt-related transcription factor-2 (RUNX2), osteocalcin] was detected by quantitative real-time PCR (qPCR).@*Results@#Both BADSC and WADSC were osteogenic. The ALP activity of BADSC was significantly greater than that of WADSC at each time point after osteogenic induction. After 5 weeks of osteogenic induction, BADSC formed a larger area of calcium nodules (accumulated optical density was 92 558±1 507), which was significantly greater than WADSC (accumulated optical density was 52 319±1 786) (t=29.81, P<0.05). The expression of BADSC osteogenic marker genes (RUNX2 and osteocalcin) was significantly higher than that of WADSC (P<0.05).@*Conclusions@#Both BADSC and WADSC have the potential for osteogenic differentiation, but BADSC has better osteogenic differentiation ability than WADSC.

Major diagnostic signs of magnetic resonance imaging for uterine adenomyosis / 第二军医大学学报

Objective To investigate the value of abnormal thickening of the junctional zone, and T1 weighted imaging (WI) and (or) T2WI hyperintense in magnetic resonance imaging (MRI) for the diagnosis of uterine adenomyosis. Methods The MRI images of 37 cases of adenomyosis confirmed by pathology in Changhai Hospital of Navy Medical University (Second Military Medical University) from Jan. 2013 to Jan. 2016 were retrospectively analyzed, and 37 cases of normal uterus and ovary confirmed by MRI in the same period were randomly selected as controls. The maximal junctional zone thickness (JZmax), the difference between the smallest and largest junctional zone thickness (JZdiff), and the ratio of JZmax to maximal myometrium thickness (JZmax/ Mmax) were measured and compared between the two groups. The receiver operating characteristic (ROC) curve of each parameter in diagnosis of adenomyosis was drawn, and the area under curve (AUC), cut-off value, sensitivity, specificity and accuracy were calculated. In addition, the T1WI and T2WI hyperintense and their types in the uterine wall were observed. Results There were significant differences in JZmax, JZdiff and JZmax/Mmax between the adenomyosis and control groups (all P<0.01). The AUC for the diagnosis of adenomyosis by JZmax JZdiff, and JZmax/Mmax were 0.95, 0.90, and 0.85, respectively. When JZmax≥10 mm, the sensitivity, specificity and accuracy were 78.8%, 97.3% and 88.6%, respectively; when JZdiff≥3.4 mm, those were 81.8%, 91.9% and 87.1%, respectively; When JZmax/Mmax≥61%, those were 72.7%, 83.8% and 78.6%, respectively. Eighteen cases (48.6%) had only T2WI hyperintense, while 14 cases (37.8%) had both T1WI and T2WI hyperintense; most of them showed snowdrift sign on T1WI and (or) T2WI. T1WI and (or) T2WI showed linear stripe sign in 5 cases (13.5%), microcapsule sign in 5 cases (13.5%), and cystic hemorrhage syndrome in 1 case (2.7%). Conclusion JZmax≥10 mm, JZdiff≥3.4 mm and JZmax/Mmax≥61% have significant diagnostic value in diagnosis of adenomyosis, and JZmax has the best diagnostic efficiency. Snowdrift sign, linear stripe sign, microcapsule sign and cystic hemorrhage sign on T1WI and (or) T2WI are unique for the diagnosis of adenomyosis. Comprehensive evaluation of the above signs can improve the diagnostic value of MRI and early accurate diagnosis of adenomyosis.

CRISPR/Cas9 and its application in drugs development / 药学学报

CRISPR/Cas9 system, consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages. A simple version of the CRISPR/Cas system, type Ⅱ CRISPR, has been modified to edit genomes. By delivering the Cas9 nuclease together with a synthetic guide RNA (sgRNA) into cells, genome can be edited at desired loci site. CRISPR/Cas genome editing techniques have been widely implemented in various species and research areas. In this review, we summarize the several applications of CRISPR/Cas9 in the field of drug discovery and development, which include target gene screening and editing, drug target screening and validation, generation of animal models and treatment of genetic disease, etc. The defects and improvements of CRISPR/Cas9 technology is discussed as well.