Clinicopathological features of fibrin-associated diffuse large B-cell lymphoma: a report of six cases / 中华病理学杂志

Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.

Bone-derived MSCs encapsulated in alginate hydrogel prevent collagen-induced arthritis in mice through the activation of adenosine A2A/2B receptors in tolerogenic dendritic cells

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Anti-colorectal cancer mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma based on network pharmacology and experimental verification / 中国中药杂志

The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and β-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.

Therapeutic effect of compound acid, alpha hydroxyl acid and salicylic acid on acne vulgaris: a comparative study / 中华医学美学美容杂志

Objective:To evaluate the curative effect and adverse reactions of compound acid, alpha hydroxyl acid (AHA), and salicylic acid (SA) in the treatment of mild to moderate acne.Methods:A total of 105 patients admitted in Suzhou Municipal Hospital from August 2019 to May 2020 were divided into three groups randomly and treated with compound acid, AHA and SA, once every 3 weeks, 4 times totally. The efficacy was evaluated before treatment, 3 weeks after 1 time, 2 times, 3 times, and 4 times. The number of non-inflammatory lesions (comedos) and inflammatory lesions (papules or pustules) were recorded. VISIA image was used to record the patient＇s facial characteristics before treatment and 3 weeks after 4 times. The occurrence of adverse reactions was recorded.Results:Three groups were all safe and effective. The efficiency of non-inflammatory lesions showed that there was no statistically significant difference between the 3 groups (χ 2= 4.58, P=0.101). The effective rate of inflammatory lesions in the compound acid and SA groups were higher than that of AHA group, and the difference was statistically significant (χ 2=6.45, P=0.040). After 4 times, the clinical data of purpurin, red area, and spot in compound acid and SA groups were higher than those before treatment, and the difference was statistically significant ( P<0.05). While in the AHA group, the purple matter was higher than that before treatment after 4 times, the difference was statistically significant ( t=3.506, P=0.010), and the change in the red area was not statistically significant ( P>0.05). Conclusions:The compound acid is safe and effective in treating mild and moderate acne. It is effective for acne inflammatory and non-inflammatory lesions. It has less adverse reactions and is worthy of clinical application.

Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Astragali Radix-Curcumae Rhizoma （AC） in inhibiting tumor growth in the orthotopic transplantation model of colon cancer in mice. Method:The molecular docking technology was used to predict the intermolecular interaction between the main active components of AC and the pathway target proteins， such as stromal cell-derived factor-1 （SDF-1）， C-X-C motif chemokine receptor 4 （CXCR4）， and nuclear factor kappa-B p65 （NF-<italic>κ</italic>B p65）. The orthotopic transplantation model of CT26.WT colon cancer was established in mice for <italic>in vivo</italic> experimental verification. Sixty BALB/c male mice were randomly divided into a sham operation group， a model group， a 5-fluorouracil （5-Fu， 30 mg·kg^-1） group，and low- （0.32 g·kg^-1）， medium- （0.64 g·kg^-1）， and high-dose （1.28 g·kg^-1） AC groups， with 10 mice in each group. The sham operation group and the model group received normal saline by gavage. The corresponding drugs were administered by gavage in the 5-Fu group and by intraperitoneal injection in the AC groups. After intervention for 15 days， the tumor <italic>in situ</italic> was completely stripped， and the colon tissues 5-6 cm in length adjacent to the tumor were taken. The tumor volume was measured and calculated. The pathological changes of tumor tissues and colon tissues were observed by Hematoxylin-Eosin （HE） staining. Western blot was used to detect the protein expression of SDF-1， CXCR4， p-NF-<italic>κ</italic>B p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect SDF-1， CXCR4， NF-<italic>κ</italic>B p65， Cyclin D₁， oncogene c-Myc protein and mRNA expression in tumor tissues. Result:Compared with the model group， 5-Fu and AC groups showed reduced tumor volumes <italic>in situ</italic> （<italic>P</italic><0.05， <italic>P</italic><0.01）， with the tumor inhibition rate in the 5-Fu group as high as （61.38±2.34）%. The tumor-inhibiting effect was optimal in the medium-dose AC group， with the tumor inhibition rate of （43.43±3.71）%. Compared with the model group， 5-Fu and AC groups showed relieved pathological changes of tumor and colon tissues. Specifically， AC down-regulated the protein expression levels of SDF-1， CXCR4， and p-NF-<italic>κ</italic>B p65 in colon tissues （<italic>P</italic><0.01）， and down-regulated the protein and mRNA expression levels of SDF-1， CXCR4， NF-<italic>κ</italic>B p65， Cyclin D₁， and c-Myc in tumor tissues （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:AC can inhibit the growth of orthotopic transplantation tumor of colon cancer， and its intervention mechanism may be related to the regulation of related protein and mRNA expression in the SDF-1/CXCR4/NF-<italic>κ</italic>B signaling pathway.

Analysis of the status and influencing factors of exercise and exercise self-efficacy in middle-aged and elderly patients with hypertension / 公共卫生与预防医学

Objective To analyze the current status of exercise and exercise self-efficacy (ESE) and its influencing factors in middle-aged and elderly patients with high blood pressure, and to provide a basis for the intervention of patients with hypertension in the community. Methods The stratified random sampling method was used to select 546 patients with hypertension who had received hypertension management for one year in the community. The general condition, exercise condition, and ESE scores were collected using survey questionnaires. Chi-square test was applied to analyze the difference of exercise efficacy score among different characteristic objects, and analysis of regression method was applied to analyze the influencing factors of exercise self-efficacy. Results A total of 546 people were surveyed in this study, of which 67.03% of hypertension patients participated in exercise. The main exercise program was walking healthily (87.43%). A total of 262 people (47.99%) had strong performance on ESE score, while 284 people (52.01%) had weak self-efficacy. The univariate unconditional logistic regression analysis found that there were significant differences in the distribution of educational level, family monthly income, years of hypertension, whether they received the guidance from family doctors, whether they exercised and whether they warmed up before exercise (P<0.05). The multivariate unconditional logistic regression analysis showed that educational level of junior high school and low average monthly household income were the risk factors affecting exercise efficacy, and the guidance of family doctors, exercise, and hypertension less than 5 years were the protective factors affecting exercise efficacy. Conclusion The exercise self-efficacy of middle-aged and elderly patients with hypertension in this community is at a medium level, and family doctors should carry out targeted interventions based on influencing factors to improve exercise self-management ability.

Effect of resveratrol on PTEN expression and fibrosis of renal tubular epithelial cells in a high-glucose environment / 中国中药杂志

This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 μmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.

Mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on intervention of cerebral ischemia based on network pharmacology-molecular docking / 中国中药杂志

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.

Study on intervention effect of Astragali Radix-Curcumae Rhizoma on growth and metastasis of colon cancer in orthotopic transplantation mice model of colon cancer / 中国中药杂志

Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(β-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of β-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.

Effect of salvianolic acid B on high-glucose induced renal tubular epithelial-mesenchymal transition in rats and its mechanism / 中国中药杂志

The aim of this paper was to observe the effect of salvianolic acid B(Sal B) on high-glucose induced renal tubular epithelial-mesenchymal transition(EMT) in rats, and to explore its possible mechanisms of prevention and treatment of diabetic nephropathy. The rat renal tubular epithelial NRK-52 E cells were cultured in vitro. The cells were divided into control group, high glucose group, high glucose+10 μmol·L~(-1)Sal B group(Sal B), the above 3 groups were set at 6, 12, 24 and 48 h for dynamic observation; high glucose+Sal B different concentration(1, 5, 10 μmol·L~(-1)) groups, high glucose+5.0 μmol·L~(-1) pioglitazone group, high glucose+10 μmol·L~(-1)Sal B+5 μmol·L~(-1)GW9662 group. The protein expression levels of PPARγ, PTEN, α-SMA, E-cadherin and PI3 K/Akt signaling molecules were determined by Western blot. The mRNA expression of PPARγ and PTEN were detected by Real-time PCR. The viabi-lity of NRK52 E cells was determined by MTT assay. The results showed that as compared with control group, the mRNA and protein expression levels of PPARγ and PTEN in high glucose group gradually reduced, the protein expression levels of α-SMA and p-Akt~((Thr308))gradually increased, and the protein expression of E-cadherin gradually reduced(P<0.05). As compared with high glucose group, when increases in Sal B doses, the mRNA and protein expression levels of PPARγ, PTEN in high glucose + different concentrations of Sal B groups gradually increased, the protein expression levels of α-SMA and p-Akt~((Thr308)) gradually reduced, and the protein expression of E-cadherin gradually increased(P<0.05), however, the effect of 1 μmol·L~(-1)concentration of Sal B on the expression of PPARγ mRNA and protein and PTEN mRNA was not significantly different. As compared with high glucose group, the mRNA and protein expression levels of PPARγ mRNA(except 6 h) and protein(except 6 h), PTEN mRNA(except 6 h) and protein(except 6, 12 h) kept increasing, the protein expression levels of α-SMA and p-Akt~((Thr308))(except 6 h) continued to reduce, the protein expression of E-cadherin kept increasing in high glucose+10 μmol·L~(-1) Sal B dynamic observation group(P<0.05). As compared with high glucose group, Sal B and the pioglitazone(PIO) can greatly enhance the expression of PPARγ, PTEN at mRNA and protein levels, enhance the expression of E-cadherin at protein levels, and reduce the expression of α-SMA, p-Akt~((Thr308))protein level(P<0.05), there was no significant difference between the two groups. However, the expression levels of PPARγ and PTEN mRNA and protein, E-cadherin, α-SMA and p-Akt(Thr308) protein in the Sal B+GW9662 control group were not statistically significant compared with the high glucose group. The effect of Sal B was blocked by the PPARγ antagonist GW9662. It can be concluded that Sal B can suppress the NRK52 E cells induced by high-glucose EMT. The mechanism may be related to the activation of PPARγ with Sal B, and the up-regulation of PTEN expression, and thereby inhibiting the fibrosis effect of PI3 K/Akt signaling pathway.

Suberoylanilide hydroxamic acid overcomes erlotinib-acquired resistance via phosphatase and tensin homolog deleted on chromosome 10-mediated apoptosis in non-small cell lung cancer / 中华医学杂志(英文版)

BACKGROUND@#Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.@*METHODS@#An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.@*RESULTS@#The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.@*CONCLUSIONS@#PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

Effects and Mechanism Study of Pioglitazone on High Glucose-induced Epithelial-mesenchymal Transition in Renal Tubular Epithelial Cells of Rat / 中国药房

OBJECTIVE：To investigate the effects o f pioglitazone （PIO）on high glucose-induced epithelial-mesenchymal transition（EMT）in renal tubular epithelial cells of rat and its possible mechanism ，and to provide theoretic reference and new target for the prevention and treatment of diabetic nephropathy. METHODS ：The rat renal tubular epithelial NRK- 52E cells were randomly divided into control group （5.5 mmol/L glucose ），high-glucose group （30 mmol/L glucose ），PIO intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO），GW9662 intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO+5.0 μmol/L specific anta- gonist GW 9662）. The cells of the first 3 groups were detected at 6，12，24，48 h of culture ，while those in GW 9662 intervention group were detected at 48 h of culture. mRNA expression of PTEN and PPARγ were detected by real-time PCR. The protein expression of PTEN ，PPARγ，α-SMA and E-cadherin as well as the changes of PI 3K/AKT signaling pathway were determined by Western blotting assay. RESULTS ：With the extension of culture time ，compared with control group ，the mRNA and protein expression of PPARγ（except for protein expression at 6 h）and PTEN in high-glucose group reduced significantly ，while the protein expression of α-SMA and p-AKT （Thr308）increased significantly ，and the protein expression of E-cadherin reduced significantly （P＜0.05），showing time-dependent trend. Compared with high-glucose group ，the mRNA and the protein expression （except for 6 h） of PPAR γ and PTEN were increased significantly in PIO intervention group ， while the protein expression of α-SMA and p-AKT （Thr308） were decreased significantly，and the protein expression of E-cadherin wasincreased significantly （P＜0.05）， showing time-dependent trend. There was no statistical significance in mRNA and protein expression of PPAR γ and PTEN，protein expression of E-cadherin ，α-SMA and p-AKT （Thr308） between GW 9662 intervention group and high-glucose group ；the effect of PIO was blocked by PPAR γ antagonist GW9662. CONCLUSIONS ：PIO may up-regulate the expression of PTEN by activating PPARγ，inhibit PI 3K/AKT signaling pathway so as to inhibit the occurrence of EMT of renal tubular epithelial cells .

Efficacy of nalbuphine combined with propofol for esophageal dilation with gastroscope in pediatric patients / 中华麻醉学杂志

Objective:To evaluate the effect of nalbuphine combined with propofol for esophageal dilation with gastroscope in the pediatric patients.Methods:A total of 150 pediatric patients with esophageal stenosis, aged 6 months-2 yr, weighing 6-15 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective painless balloon dilation with gastroscope under general anesthesia, were randomized into 3 groups ( n=50 each) according to the random number table method: nalbuphine 0.1 mg/kg plus propofol group (N 1P group), nalbuphine 0.2 mg/kg plus propofol group (N 2P group), and fentanyl plus propofol group (FP group). Nalbuphine 0.1 and 0.2 mg/kg and fentanyl 1 μg/kg were intravenously injected in N 1P, N 2P and FP groups, respectively, and 2 min later propofol 1.5-2.0 mg/kg was intravenously injected for sedation until the eyelash reflex disappeared in the three groups.Propofol 1.0 mg/kg was added when body movement occurred during surgery.The amount of propofol consumed during surgery, occurrence of body movement and respiratory depression, occurrence of adverse reactions such as postoperative nausea and vomiting, and laryngospasm, emergence time, Face Legs Activity Cry Consolability (FLACC) pain scale score and surgeons′ satisfaction were recorded. Results:Compared with group N 1P, the consumption of propofol, body movement classification ratio and FLACC score were significantly decreased, and the emergence time was shortened in group N 2P ( P<0.05), and no significant change was found in the parameters mentioned above in group FP ( P>0.05). There was no significant difference in the incidence of perioperative adverse reactions and degree of surgeons′ satisfaction among the three groups ( P>0.05). Conclusion:Nalbuphine combined with propofol can provide satisfactory anesthetic efficacy with fewer adverse reactions when used for esophageal dilation with gastroscope in the pediatric patients.

Preparation of a co-amorphous form of bexarotene-PVP-K30 and evaluation in rats / 药学学报

Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.

Analysis of visual acuity and refractive status of kindergarten children and primary and middle school students in a community in Shanghai 2015-2018 / 公共卫生与预防医学

Objective To analyze the visual acuity and refractive status of kindergarten children and primary and middle school students in Xinhong Community of Shanghai from 2015 to 2018, and to provide basis and reference for the prevention and control of students' myopia. Methods The data of 3 904 person-times of complete visual acuity and refraction records from 2015 to 2018 was derived from the "Shanghai Residents' Eye Health Information Service System". Results From 2015-2018, the total detection rate of poor vision of kindergarten children and primary and middle school students was 60.86%, and the detection rate of poor vision in kindergarten, primary school and middle school was 29.90%，62.63% and 87.26% respectively，showing an increasing trend with the education stage (χ2=727.206，P2=19.949, P2=1099.978, P<0.05). In terms of growth rate, the increase in myopia in the first grade of primary school was the largest. Conclusion The myopia rate of primary and secondary school students was higher than that of kindergarten children, and showed an increasing trend with the education stage. The critical period of myopia prevention and control should be advanced to the kindergarten stage.

Research progress on regulation of signaling pathway by microRNA in phenotypic change of vascular smooth muscle cell / 药学学报

A change in vascular smooth muscle cell (VSMC) phenotype, known as converting from a contractile state into a synthetic phenotype, is a crucial event in vascular remodeling, which determines the occurrence, development and prognosis of cardiovascular diseases such as pulmonary hypertension and atherosclerosis. Research shows that the expression level of key signaling molecules, which controls the phenotype change of VSMC, is regulated by microRNA (miRNA), a type of non-encoding RNA. In this article, we provide a review of miRNA in the regulation of VSMC phenotype changes with a focus on the key molecules in MAPK, TGFβ/Smad and PI3K/Akt signaling pathways.

Expression of WNT4 and its inhibitory factor SFRP1 in renal tissue of diabetic nephropathy rats / 基础医学与临床

Objective To observe the change of expression of WNT4/β-catenin signaling pathway and its inhibitory factor secreted frizzled-related protein 1 (SFRP1) in renal tissue in diabetic nephropathy(DN) rats, and to explore its possible role in the development of renal fibrosis. Methods Rats were randomly divided into normal control(NC) group and DN group, and equipped with 8 in each group. The IDDM model was prepared by tail vein injection of STZ 55 mg/kg. Hemotoxyin and eosin、Periodic Acid-Schiff and Masson stain were used to observe the morphological structure and fibrotic lesions in renal tissue;Immunohistochemical analysis was used to observe the protein expression of WNT4 and β-catenin in renal tissue;Western blot was used to detect the protein expression changes of WNT4, SFRP1, β-catenin, p-GSK-3β, GSK-3β, Collagenl, a-SMA, E-cadherin in renal tissue in each group;The mRNA expression of WNT4 and SFRPl in renal tissues of rat was detected by realtime PCR. Results Compared with NC group, renal tissue fibrosis was obvious in DN group. Compared with NC group, the protein and mRNA expressions of WNT4 significantly increased (P＜0.05), the protein expressions of β-catenin, p-GSK-3β, α-SMA and collagen I significantly increased (P < 0.05), the protein expressions of Ecadherin significantly decreased (P＜0. 05), the protein and mRNA expression of SFRPl significantly decreased (P＜0.05). Conclusions In the case of DN, the signal pathway of WNT4/β-catenin is abnormal activation. The expression of SFRPl is decreased, and that may inhibit this pathway and promote the development of renal fibrosis in DN.

Repair of corneal ulcer or perforation using the corneal stromal lenticule / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To describe the outcomes of corneal stromal lenticules in repairing of corneal ulcer and/or perforation.METHODS:This was a retrospective chart review of 6 eyes of 6 patients from January to June 2017,who underwent corneal ulcer repair with the corneal,stromal lenticules harvested from femtosecond laser refractive surgery and kept in pure glycerin for use.Three cases of infectious corneal ulcers were bacterial,fungal,and infection with foreign bodies in corneal deep layer,one each.The other 3 were corneal ulcer perforation.Making sure no air bubble between donor graft and Descemet membrane.The mean follow-up time was 3.71 ±1.56mo (range 1-6mo).RESULTS:All eyes were successfully treated under control of infection without intra-operative complications,and early postoperative evaluation showed a clear graft in all cases.The last follow-up visit showed the mean best corrected visual acuity (VA) significantly improved after surgery.There was significant difference from 0.48±0.12 to 1.50±0.08 (P＜0.01).CONCLUSION:The preliminary results suggest that the use of corneal stromal lenticules may be a safe and effective surgical alternative for corneal ulcer,even though the long-term outcome of the graft needs to be further observed.

Management of patients with chronic kidney disease in the community / 中华全科医师杂志

Huacao Community Health Service Center has established an integrated chronic kidney disease (CKD) management system since 2015,which greatly improved CKD management in the community.From September 2016 to August 2017,4084 residents were screened by the family doctor team,975 were suspected to have CKD (23.87％),among whom 202 (20.72％) were referred to district CKD treatment center,and 197 (97.52％) were confirmed as CKD.The detection rate of suspected CKD among patients with hypertension and diabetes mellitus was the highest,which was much higher than that among outpatients and those with routine health check up.It is suggested that the integrated management of CKD should be widely implemented to cope with the prevalence of CKD,particularly for those with hypertension and diabetes.

Facial cutaneous phaeohyphomycosis caused by Microsphaeropsis arundinis: a case report / 中华皮肤科杂志

A 55-year-old male patient presented with plaques on the face for more than 20 years,and no immunodeficiency diseases were diagnosed.Skin examination showed large areas of pink plaques on the nose,bilateral cheeks and upper oral lips with slight desquamation,verrucous hyperplasia on the dorsal area of the nose,and a bean-sized verrucous protuberance on the tip of the nose.Histopathological examination of the skin lesions revealed pseudoepitheliomatous hyperplasia in the epidermis and hyphae-like structures in the stratum corneum.Moreover,there was diffuse infiltration of inflammatory cells in the dermis,which mainly included neutrophils,lymphocytes,histiocytes and multinucleated giant cells.Periodic acid-Schiff (PAS)-positive spore-like structures were observed in the multinucleated giant cells.Culture of the lesional tissues on Sabouraud dextrose agar (SDA) medium showed grey-brown villous colonies.Microculture on the potato dextrose agar (PDA) medium yielded dark septate hyphae and pycnidia filled with a large number of spores.Microsphaeropsis arundinis was identified by fungal molecular biological techniques.The patient was diagnosed with cutaneous phaeohyphomycosis caused by Microsphaeropsis arundinis.The patient was treated with CO2 laser for the removal of verrucous protuberance on the tip of the nose,and oral itraconazole capsules at a dose of 200 mg twice a day.After 3-month treatment,the skin lesions subsided and the drug was withdrew.During 6-month follow-up,no relapse occurred.