Development and future promise of salivary gland organoids and salivary gland tumor organoids / 中华口腔医学杂志

Salivary glands are important organs in the oral and maxillofacial region. Environment and genetic factors may cause salivary gland tumors or non-neoplastic diseases, but the mechanisms of those diseases are still unclear. One of the important reasons is the short of researching media and model. As a new technique and research model, organoids have been widely used in the research of various diseases. Organoid culture plays a bridging role between two-dimensional cell culture and living animal models, and it is also the most promising translational research model that could connect the clinical research to basic research. This review will discuss the recent development of organoid techniques in the culture of normal salivary glands and salivary gland tumors, also their applications and challenges in tissue engineering, etiological research, and tumor therapy.

Radiofrequency deep hyperthermia combined with chemotherapy in the treatment of advanced non-small cell lung cancer / 中华医学杂志(英文版)

BACKGROUND@#In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion.@*METHODS@#We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant.@*RESULTS@#Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs. 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs. 46.7%, χ = 13.16, P < 0.001) and gastrointestinal (25.0% vs. 77.8%, χ = 25.88, P < 0.001) adverse reactions than that in CT group. The objective tumor response and survival showed no significant differences.@*CONCLUSIONS@#Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients. Also, it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.

Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental Abnormality in the Mouse Brain / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality.</p><p><b>METHODS</b>The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells. In addition, the regulation of Nr2e1 expression by RA was also determined in vitro.</p><p><b>RESULTS</b>Nr2e1 expression was significantly downregulated in the brain and NSCs of RA-treated mouse embryos, and knockdown of Nr2e1 affected the proliferation of NSCs in vitro. In addition, a similar expression pattern of Nr2e1 and RA receptor (RAR) α was observed after treatment of NSCs with different concentrations of RA.</p><p><b>CONCLUSION</b>Our study demonstrated that Nr2e1 could be regulated by RA, which would aid a better understanding of the mechanism underlying RA-induced brain abnormality.</p>

Reason analysis and preventive treatment countermeasure of impaired vision after LASlK / 国际眼科杂志(Guoji Yanke Zazhi)

To analyze the reasons of impaired vision after LASlK and explore its preventive treatment measures preliminarily.METHODS: ln this retrospective study, 175 eyes of 134 patients whose vision was decreased after LASlK were included. The constituent ratio of every reason was counted and uncorrected visual acuity ( UCVA ) between pre-treatment and post-treatment were compared by paired t-test respectively.RESULTS:The overall incidence of impaired vision after LASlK was 1. 86%. The constituent ratio of regression was 51. 43% and UCVA increased from 0. 61±0. 22 to 0. 90±0. 38 (t=8. 00, P<0. 001) after treatment. The constituent ratio of punctate corneal epithelial defect was 32. 57% and UCVA increased from 0. 60±0. 19 to 1. 20±0. 24 (t=20. 00, P<0. 001 ) after treatment. The constituent ratio of accommodative spasm was 5. 14% and UCVA increased from 0.76±0. 21 to 1. 32±0. 22 (t=8. 14, P<0. 001) after treatment. The constituent ratio of corneal flap shift and gauffer was 4% and UCVA increased from 0. 29 ± 0. 26 to 1. 24 ± 0. 28 ( t = 6. 33, P<0. 001 ) after treatment. The constituent ratio of corticosteroid - induced ocular hypertension was 4% and UCVA increased from 0. 57±0. 05 to 1. 0 ± 0. 16 ( t= 2. 53, P<0. 05 ) after treatment. The constituent ratio of fundus lesions and diffuse lamellar keratitis ( DLK) was 2. 86% and UCVA all increased by different degrees after treatment.CONCLUSlON: The reasons of impaired vision after LASlK are many and varied. These cases could recover their vision by discovery and treatment in time, and the appropriate preventive measures were essential.

Sinistral portal hypertension caused by body and tail tumors of the pancreas in 40 cases / 中华普通外科杂志

Objective To evaluate the clinical characteristics,diagnosis and treatment method of pancreatic sinistral portal hypertension caused by tumors in the body and tail of the pancreas.Methods A retrospective review of 40 patients diagnosed with pancreatic sinistral portal hypertension at Peking Union Medical College Hospital from January 2007 to December 2012 was performed.Results The Initial symptoms were epigastric pain and discomfort (n =12),emaciation (n =5),low-back pain (n =4),splenomegaly (n =2),hematemesis and melena (n =4),hypoglycemic coma (n =1).All 40 patients had splenomegaly and varices in the gastric fundus with normal liver function.8 had combined esophageal varices.24 had hypersplenism and 26 had elevated serum CA19-9 level.25 patients received surgical intervention and 15 were treated conservatively.Pathology confirmed malignancy in 29 patients and benign lesions in 11.Thirty-five patients (35/40,88％) were followed up for 12 to 72 months.For patients undergoing surgery,hypersplenism and varices in the gastric fundus were all relieved.There was no upper gastrointestinal bleeding occurred during follow-up.For patients treated conservatively,hypersplenism remained stable and among them 4 patients had upper gastrointestinal bleeding,and successfully treated by medication,therapeutic endoscopy and interventional therapy.Conclusions Patients with pancreatic sinistral portal hypertension caused by tumor in the body and tail of the pancreas can be cured successfully by surgery.In those patients portal hypertension can present as initial clinical manifestation.

In vitro differentiation of islet-like cells from mouse bone-marrow stem cells on a PLGA scaffold / 国际生物医学工程杂志

Objective To investigated the potential influences of poly(lactic-co-glycolicacid)(PLGA)scaffold as a platform on the differentiation of mouse bone-marrow stem cells to islet-like cells.Methods Mouse bonemarrow stem cells were grown and differentiated in culture with or without PLGA scaffold,and cell morphology and functions were compared within these groups.Results The PLGA scaffold showed fine biological compatibility.Differentiated islet-like cells were dithizone (DTZ) positive,insulin and C-peptide double positive,glucagon positive and somatostatin positive in both groups.Under electron microscope there were ultrastructures similar to that of islet β cells in cells of both groups.Cells with PLGA scaffold secreted more insulin under high level glucose stimulation (P＜0.01).Conclusions PLGA scaffold was biologically compatible and improved function of the differentiated islet-like cells.

Structure-based identification of drug-like inhibitors of p300 histone acetyltransferase / 药学学报

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.

Pathological and high resolution CT findings in Churg-Strauss syndrome / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis.</p><p><b>METHODS</b>We retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well.</p><p><b>RESULTS</b>The patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months).</p><p><b>CONCLUSIONS</b>Asthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.</p>

Effect of nano-hydroxyapatite to glass ionomer cement / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanical character, microleakage and mineralizing potential of nano-hydroxyapatite (nano-HAP)-added glass ionomer cement(GIC).</p><p><b>METHODS</b>8% nano-HAP were incorporated into GIC as composite, and pure GIC as control. Both types of material were used to make 20 cylinders respectively in order to detect three-point flexural strength and compressive strength. Class V cavities were prepared in 120 molars extracted for orthodontic treatment, then were filled by two kinds of material. The microleakage at the composite-dentine interface was observed with confocal laser scanning microscope (CLSM) after stained with 1% rhodamin-B-isothiocyanate for 24 hours. Class V cavities were prepared in the molars of 4 healthy dogs, filled with composite, and the same molars in the other side were filled with GIC as control. The teeth were extracted to observe the mineralizing property with polarimetric microscope in 8 weeks after filling.</p><p><b>RESULTS</b>Three-point flexural strength and compressive of nano-HAP-added GIC were increased compared with pure GIC (P < 0.001, P < 0.05). The nanoleakages and microleakages appeared at the material-dentine interface in the two groups, but there were more microleakages in control group than in experiment group (P = 0.004). New crystals of hydroxyapatite were formed into a new mineralizing zone at the interface of tooth and nano-HAP-added GIC, while there was no hydroxyapatite crystals formed at the interface of tooth and pure GIC.</p><p><b>CONCLUSION</b>8% nano-HAP-added GIC can tightly fill tooth and have mineralizing potential, and can be used as liner or filling material for prevention.</p>

Effect of TRAIL gene in human squamous cell carcinoma cell line induced by adenovirus / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the apoptotic effect on the squamous cell carcinoma cell line TCa83 induced by recombined adenovirus vector containing TRAIL gene and CMV promoter.</p><p><b>METHODS</b>The TCa83 cell line was firstly infected with different titre of AdCMV-EGFP containing enhanced green fluorescence protein gene (EGFP) as control, and investigated the transducing rate through fluorescence to obtain the definite titre. Then TCa83 cell line was infected with AdCMV-TRAIL in proper titre, and TRAIL gene was detected by means of RT-PCR. After TCa83 cell line was infected with AdCMV-TRAIL and AdCMV-EGFP at day 1, 3, 5, 7, the activity of TCa83 cell line were evaluated by MIT and the apoptosis were detected by flow cytometer.</p><p><b>RESULTS</b>Proper titre was of 1,000 particles/cell, and TCa83 cell line could be infected 100% in this titre. TRAIL gene was detected by RT-PCR after infected with AdCMV-TRAIL. The activity of TCa83 decreased in both groups, but the AdCMV-TRAIL group decreased more sharply than AdCMV-EGFP group (P < 0.001). Both AdCMV-TRAIL and AdCMV-EGFP could lead to apoptosis of TCa83 cells, but the AdCMV-TRAIL, function stronger than AdCMV-EGFP. Especially there was remarkable statistic difference between two groups (P < 0.0001).</p><p><b>CONCLUSION</b>AdCMV-TRAIL could effectively decrease the activity of TCa83 cell line and induce apoptosis.</p>

Study of methods of decalcification for making united slices of tooth and affiliated periodontic tissues / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the methods of decalcification for making united slices of tooth and affiliated periodontic tissues.</p><p><b>METHODS</b>Twenty-one samples containing dog molars and affiliated periodontic tissues were divided into seven mean groups. The pH value of solution, time of decalcification, weight and volume of samples, and content of decalcified calcium were detected. The slices were observed by HE, specific, and immunohistochemical stain.</p><p><b>RESULTS</b>The velocity of decalcification increased with decrease of solution pH. The weight of samples lightened by 37.61%, the volume reduced by 25.97% on average, and calcium decalcified was 174.49 mg per gram humid samples. The EDTA decalcification was slowest, but it was best. Decalcification was fast in Plank-Rycho solution while the section was worst, and faster in the formyl solution containing aluminium chloride than in EDTA, and the section was better.</p><p><b>CONCLUSIONS</b>The 50% formyl solution containing aluminium chloride is an ideal decalcifying solution.</p>

Population Polymorphism of Trypanosoma cruzi in Latin America indicated by Proteome analysis and by in vitro amastigote proliferation

Nineteen stocks of <I>Trypanosoma cruzi</I> originating from several endemic countries for Chagas‘ disease in Central and South America were subjected to two-dimensional protein electrophoresis analysis. The presence or absence of a total of492polypeptide spots among19gel profiles was determined. The stocks were classified into three major distinctive groups derived from (I) Central America and the northern part of South America; (IIa) Central America and the northern part of South America; and (IIb) central and southern parts of South America, which showed perfect concordance with the previously reported classification based on isozyme and DNA sequence analyses. Late log phase of each epimastigote was inoculated to human cell lines WI-38and Hs224.T originating from the lung and muscle, respectively, and the number of trypomastigotes released was counted. The number of trypomastigotes from <I>T</I>. <I>cruzi</I> in group I released from the two cell lines was significantly higher than that in group III (p&It;0.05). The findings suggested that the phenetic distance appearing within the <I>T</I>. <I>cruzi</I> may, to some extent, be associated with the intracellular growth of <I>T</I>. <I>cruzi</I>, one of the characteristic features of growth found in the species.

Establishment of an IR-HIRc cell model for screening GFAT inhibitor / 药学学报

<p><b>AIM</b>To set up an IR-HIRc cell model for screening the inhibitor of GFAT (glutamine: fructose-6-phosphate amidotransferase) , the key enzyme in the hexosamine biosynthesis pathway (HBP).</p><p><b>METHODS</b>For GFAT activity assay, the GDH method was improved by adjusting the value of pH in the reaction system and the concentrations of the reactants. The sensitivity to insulin in the cells was estimated by the measurement of insulin-induced glucose-uptake. The IR-HIRc model was set up by the stimulation of long-action insulin for 36 h. The IR-HIRc model and GDH method was used for screening GFAT inhibitor.</p><p><b>RESULTS</b>With the administration of 25 nmol x L(-1) long-action insulin in HIRe cells for 36 hours, the GFAT activity increased by 47% and the insulin-induced glucose-uptake decreased by 21%. Azaserine, a GFAT inhibitor, inhibited GFAT activity significantly in a dose-dependent manner in IR-HIRc model.</p><p><b>CONCLUSION</b>With the stimulation of 25 nmol x L(-1) long-action insulin for 36 h, excess hexosamine flux and insulin resistant in IR-HIRc cell model was set up, which can be used for screening</p>

Effects of L.F04, the active fraction of Lycopus lucidus, on erythrocytes rheological property / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of L.F04, the active fraction of Lycopus lucidus, on erythrocytes rheological property so as to investigate its mechanism in promoting blood circulation and removing blood stasis.</p><p><b>METHOD</b>The effects of L.F04 (used for treatment for 10 days in different dosages) on deformability, aggregation and membrane liquidity of erythrocytes (MLE) as well as whole blood apparent viscosity (eta(b)) were examined on the basis of rat model of blood-stasis syndrome induced by venous injection of high molecular weight dextran.</p><p><b>RESULT</b>As compared with the normal control group, the model group's RBC deformability and MLE were lower, and the aggregation of erythrocytes and eta(b) were higher. Compared with the model group, both L.F04 0.612 g/kg and 0.306 g/kg showed significant effect in improving deformability and inhibiting aggregation of red blood cells (RBC) and reducing blood viscosity. The trend of improving MLE was also shown.</p><p><b>CONCLUSION</b>L.F04 could significantly improve the abnormal rheological property of erythrocytes.</p>