Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics / 中华心血管病杂志

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Effect of different abutment materials on the expression of genes and proteins related to hemidesmosome adhesion in human gingival epithelial cells / 中华口腔医学杂志

Objective: To investigate the effects of polyetheretherketone, zirconium dioxide, and titanium abutment materials on the expression of genes and proteins related to hemidesmosome adhesion in human gingival epithelial cells, in order to screen out abutment materials that are easier for epithelial adhesion. Methods: Forty-eight specimens were prepared in each of the three materials, polyetheretherketone, zirconium oxide, and pure titanium specimens. The surface morphology of each group of specimens was observed by scanning electron microscopy, the surface roughness was measured by the white light interferometer, and the contact angle was measured by optical contact angle measuring instrument. The early adhesion status of human gingival epithelial cells on the surface of each group of specimens was observed by scanning electron microscopy, and the proliferation ability of human gingival epithelial cells on the surface of each group of specimens was assessed by using a cell counting kit, and the expression levels of genes and proteins related to the adhesion of human gingival epithelial cells on the surface of each group of specimens were detected by real-time fluorescence quantitative PCR and Western blotting, respectively. Results: The surface morphology of the three groups of specimens was flat and smooth. The mean roughness (Ra value) of the polyetheretherketone, zirconia, and pure titanium groups were (95.63±2.06), (37.93±3.56), and (134.2±4.62) nm (F=368.16, P<0.001), respectively, and the mean maximum height (Rz value) was (2.42±0.22), (0.87±0.10) and (3.77±0.28) nm (F=91.95, P<0.001), with statistical significance (P<0.05). The contact angles were 81.23°±0.91°, 82.08°±2.10°, and 80.47°±1.85°, respectively, with no statistically significant overall difference (F=0.45, P=0.658). Human gingival epithelial cells showed irregular shapes such as flattened and extended polygons and polygons on the surface of the three groups of specimens, exhibiting a typical paving stone pattern. The differences in cell proliferation among the three groups at 1 and 3 d of culture were not statistically significant (P>0.05). Cell proliferation in the polyetheretherketone group was significantly greater those those in the zirconia and pure titanium groups at 5 and 7 d of culture (P<0.05). The mRNA expression levels and protein expression levels of laminin α3, integrin β4, and collagen ⅩⅦ in the polyetheretheretherketone group at 3 and 7 d of incubation were significantly greater than those in the zirconium oxide and pure titanium groups at the same time points (P<0.05). Conclusions: Polyetheretherketone is more conducive to the adhesion of hemidesmosome in human gingival epithelial cells than zirconium dioxide and pure titanium abutment materials.

Analysis on infection sources and transmission chains of three outbreaks caused by 2019-nCoV Omicron variant in Beijing, China / 中华流行病学杂志

Objective: To investigate the infection sources and the transmission chains of three outbreaks caused by 2019-nCoV Omicron variant possibly spread through cross-border logistics in Beijing. Methods: Epidemiological investigation and big data were used to identify the exposure points of the cases. Close contacts were traced from the exposure points, and the cases' and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: The Omicron variant causing 3 outbreaks in Beijing from January to April, 2022 belonged to BA.1, BA.1.1 and BA.2. The outbreaks lasted for 8, 12 and 8 days respectively, and 6, 42 and 32 cases infected with 2019-nCoV were reported respectively. International mail might be the infection source for 1 outbreak, and imported clothes might be the infection sources for another 2 outbreaks. The interval between the shipment start time of the imported goods and the infection time of the index case was 3-4 days. The mean incubation period (Q1, Q3) was 3 (2,4) days and the mean serial interval (Q1, Q3) was 3 (2,4)days. Conclusions: The 3 outbreaks highlighted the risk of infection by Omicron variant from international logistics-related imported goods at normal temperature. Omicron variant has stronger transmissibility, indicating that rapid epidemiological investigation and strict management are needed.

Engineering microbial consortia through synthetic biology approach / 生物工程学报

There are a large number of natural microbial communities in nature. Different populations inside the consortia expand the performance boundary of a single microbial population through communication and division of labor, reducing the overall metabolic burden and increasing the environmental adaptability. Based on engineering principles, synthetic biology designs or modifies basic functional components, gene circuits, and chassis cells to purposefully reprogram the operational processes of the living cells, achieving rich and controllable biological functions. Introducing this engineering design principle to obtain structurally well-defined synthetic microbial communities can provide ideas for theoretical studies and shed light on versatile applications. This review discussed recent progresses on synthetic microbial consortia with regard to design principles, construction methods and applications, and prospected future perspectives.

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears / 中华烧伤杂志

Objective: To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism. Methods: Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor β1 (TGF-β1) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis. Results: On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-β1 and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-β1 and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05). Conclusions: Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-β1 and α-SMA in scar tissue.

Research progress of natural products for the treatment of hyperuricemia and gout / 药学学报

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Application value of contrast-enhanced ultrasound before and after microwave ablation of thyroid nodules / 中国基层医药

Objective:To investigate the application value of contrast-enhanced ultrasound (CEUS) before and after microwave ablation of thyroid nodules.Methods:Fifty-six patients (79 thyroid nodules) who received microwave ablation of thyroid nodules in Huaian Medical District, General Hospital of Eastern Theater Command from March 2016 to October 2019 were included in this study. CEUS was performed before microwave ablation to accurately assess the size, number and blood supply of thyroid nodules as well as the position of the feeding vessels. CEUS was performed immediately after microwave ablation to determine whether the lesion area was thoroughly ablated and to measure the volume of thyroid nodules. At 1, 3, 6 and 12 months after surgery, the level of thyroid hormone was measured and the absorption of thyroid nodules was evaluated.Results:Preoperative CEUS showed that among the 79 thyroid nodules, 42 were solid nodules that had different degrees of enhancement, including 33 annular homogeneously highly enhanced nodules and 9 heterogeneously highly enhanced nodules; 24 were cystic mixed solid nodules that had solid components, including 16 homogeneously highly enhanced nodules and 8 nodules with only local high enhancement in the solid component; 13 were cystic nodules, including 9 nodules with septa and 3 nodules with contrast medium on the diaphragm. Contrast medium was still visible around three nodules immediately after microwave ablation. Ablation continued in three nodules until there was no contrast medium. The incidence of complications during and after treatment was 0%. The average volume of the thyroid nodules before treatment was (7.52 ± 6.74) cm3. At 1, 3, 6 and 12 months after surgery, the average volume of the thyroid nodules was (6.06 ± 5.19) cm3, (3.06 ± 2.85) cm3, (1.32 ± 1.23) cm3 and (0.59 ± 0.52) cm 3, respectively. There was significant difference in volume of thyroid nodules between before and after microwave ablation ( F = 96.32, P < 0.001). Conclusion:Preoperative CEUS can determine the distribution of the blood supply of thyroid nodules and the course of the feeding vessels, identify the needle-entering position for microwave ablation and the primary ablation area, improve the accuracy of treatment, and reduce the occurrence of complications such as bleeding. Postoperative CEUS can determine whether lesion area is thoroughly ablated, reduce residual lesions and excessive ablation.

Preliminary experience of surgical treatment for torus tubarius hypertrophy in children / 中华耳鼻咽喉头颈外科杂志

Objective: To assess the incidence of symptomatic torus tubarius hypertrophy (TTH) in recurred OSA in children, and to explore the preliminary experience of partial resection of TTH assisted with radiofrequency ablation. Methods: From January 2004 to February 2020, 4 922 children, who diagnosed as OSA and received adenotonsillectomy at the Department of Otolaryngology, The 4th Medical Center of the PLA General Hospital, were retrospectively reviewed. There were 3 266 males and 1 656 females, the age ranged from 1 to 14 years old(median age of 5.0 years). Twenty-two cases were identified with recurrence of OSA syndrome, and the clinical data, including sex, age of primary operation, age of recurrence and presentation, and opertation methods were analyzed. Follow-up was carried out by outpatient visit or telephone. Graphpad prism 5.0 software was used for statistical analysis. Results: Twenty-two cases were identified as recurred OSA and received revised surgery in 4 922 cases. Among these 22 cases, 11 cases were diagnosed as TTH resulting in an incidence of 2.23‰(11/4 922), 1 case was cicatricial adhesion on tubal torus (0.20‰, 1/4 922), 10 cases were residual adenoid combined with tubal tonsil hypertrophy (2.03‰, 10/4 922). Median age of primary operation was 3.0 years (range:2.4 to 6.0 years) in 11 TTH cases. Recurrent interval varied from 2 months to 5.5 years (2.4±1.9 years) after first operation. Age of revised partial resection of TTH was 7.0±2.7 years (range: 4.0 to 12.0 years). Average time interval between primary operation and revised operation was 3.5±2.1 years (range: 0.5 to 6.0 years). Individualized treatments were carried out based on partial resection of TTH assisted with radiofrequency ablation. All of 11 cases received satisfied therapeutic results without nasopharyngeal stenosis occured. Twenty-two cases were followed up for 1.6 to 13 years (median follow-up time was 6.2 years). Conclusions: TTH contributed to recurred OSA in child. TTH might be misdiagnosed as tubal tonsil hypertrophy. Partial resection of TTH assisted with radiofrequency ablation was a safty and effective treatment.

Survey of possible aerosol transmission of a COVID-19 epidemic caused by 2019-nCoV Delta variant / 中华流行病学杂志

Objective: To investigate the epidemiological characteristics and the transmission chain of a family clustering of COVID-19 cases caused by severe acute respiratory 2019-nCoV Delta variant in Changping district of Beijing. Methods: Epidemiological investigation was conducted and big data were used to reveal the exposure history of the cases. Close contacts were screened according to the investigation results, and human and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: On November 1, 2021, a total of 5 COVID-19 cases caused by 2019-nCoV Delta variant were reported in a family detected through active screening. The infection source was a person in the same designated isolation hotel where the first case of the family cluster was isolated from 22 to 27, October. The first case was possibly infected through aerosol particles in the ventilation duct system of the isolation hotel. After the isolation discharge on October 27, and the first case caused secondary infections of four family members while living together from October 27 to November 1, 2021. Conclusion: 2019-nCoV Delta variant is prone to cause family cluster, and close attention needs to be paid to virus transmission through ventilation duct system in isolation hotels.

Incomplete concerted evolution of nrDNA ITS in Lycium / 药学学报

In this study, nrDNA ITS sequences of Lycium cultivars were sequenced and used to test the existence of incomplete concerted evolution and pseudogenes. Together with 44 ITS sequences retrieved from GenBank, the pattern of base substitutions, GC content, 5.8S conserved motifs, the minimum free energy of secondary structures, nucleotide diversity and phylogenetic relationship of the samples were analyzed. While 83 of the 144 sequences were identified as pseudogenes, the results suggested a high degree of polymorphism and putative pseudogenes in Lycium, suggesting an incomplete concerted evolution of the ITS region. ITS polymorphism and pseudogene of Lycium were systematically tested for the first time. This research provides a references for ITS sequence to be used in the study of Lycium germplasm resources and DNA barcode identification.

Effect of type 2 diabetes mellitus on mandibular bone regeneration and the expression of T helper cell 17/regulat-ory T cell-related factors in mice / 华西口腔医学杂志

OBJECTIVES@#To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.@*METHODS@#Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.@*RESULTS@#HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.@*CONCLUSIONS@#T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.

Histone methylation in mammalian follicular development / 生理学报

The normal development of follicles involves a series of complex life processes such as ordered transcriptional activation and inhibition, which is crucial for female reproductive ability. Histone methylation can change the chromatin state in cells and affect the transcription activity of genes. Current studies indicate that epigenetic modifications such as histone methylation play an important regulatory role in follicular development in female mammals. This paper summarized the relationship between H3K4, H3K9 methylation and germ cell development, their regulatory effects, including their dynamical changes during follicular development, and the progress of H3K4me3 and other histone methylation binding to promoter regions of different genes to regulate gene expression and thus affect germ cell epigenetic reprogramming, oocyte transcription, meiosis and other processes. This review will provide a reference for the study of mechanisms related to histone methylation modification and the development and maturation of gonadal parenchymal cells.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Continuous monitoring of fine particulate matter in school classrooms and assessment of students exposure level / 中国学校卫生

Objective@#To explore the status of PM 2.5 pollution in school classrooms and the student exposure level, and to provide basic data to safeguard the health of students.@*Methods@#This study continuously monitored the PM 2.5 levels of 16 naturally ventilated classrooms in eight primary and secondary schools in Jiamusi for one academic year using an online environmental monitoring instrument. At the same time, outdoor PM 2.5 data was captured for comparative research, and student exposure to PM 2.5 during school hours was evaluated.@*Results@#The average concentration of PM 2.5 in the classroom in the spring and autumn semesters was (26.93±24.7) and (31.85±30.37)μg/m 3, respectively, and the indoor/outdoor ratio ( I/O ) was 0.92 and 0.95, respectively, which indicated a strong correlation between them. The daily average concentration of all classrooms during both semesters was ( 28.93 ±26.85)μg/m 3, which was slightly higher than the average concentration of (27.53±26.53)μg/m 3 during the daytime when students were in school. In addition, the concentration on workdays was higher than that observed on weekends, and this was termed the "weekend effect". The indoor PM 2.5 concentration was lower on higher floors. The comprehensive exposure concentration of students during school was 28.48 μg/m 3 in spring semester and 31.87 μg/m 3 in autumn semester.@*Conclusion@#PM 2.5 levels in the classrooms varied according to time, the horizontal space, and the vertical space, and the level of indoor PM 2.5 pollution largely depended on outdoor pollution sources. Differences in PM 2.5 exposure were observed between.

Analysis of Predictive Value of Laboratory Indexes for Malignant Lymphoma Patients with Bone Marrow Involvement / 中国实验血液学杂志

OBJECTIVE@#To analyze the influence of bone marrow involvement (BMI) in patients with malignant lymphoma (ML) on laboratory indexes, and evaluate the laboratory markers that can be used to predict/diagnose BMI.@*METHODS@#The clinical characteristics and laboratory indexes of 137 ML patients were analyzed retrospectively, from which the indexes of BMI in ML patients was studied. The logistic regression analysis and receiver operating curve (ROC) were used to evaluate independent risk factors and predictors of BMI diagnosis in ML patients.@*RESULTS@#Compared with non-BMI group, the red blood cell distribution width, C-reactive protein, erythrocyte sedimentation rate, D-dimer, lactate dehydrogenase, alkaline phosphatase, β@*CONCLUSION@#PLT and sIL2R show good diagnostic value for ML patients with BMI.

A six-herb Chinese medicine composition ointment as a promising candidate for treatment of hypertrophic scars / 中草药·英文版

Objective: To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition (SCMC) ointment on the rabbit ear hypertrophic scar models. Methods: The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests. The SCMC ointment was prepared through emulsifying method. The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment. Results: Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements. Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading, and took an unobvious but palpable shift from hard to soft texture with the low, middle and high concentration SCMC ointments treatments in vivo. Additionally, on 21st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group, in a concentration-dependent manner. The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation. Conclusion: The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues. Our research has demonstrated the Chinese medicine composition ointment with good anti-hypertrophic scar properties that could be used to treat hypertrophic scars. Meanwhile, it provides a theoretical basis for further clinical application.

Transcriptome analysis of the transformation of podocytes into mesenchymal cells in high glucose memory model / 解放军医学杂志

Objective: To investigate, with transcriptome sequencing, the mechanism of metabolic memory in epithelial-mensenchymal transition (EMT) of podocytes induced by high glucose. Methods: Mouse glomerular podocytes were cultured in four groups: normal glucose group (NG, 5 mmol/L D-glucose X48 h); high glucose group (HG, 30 mmol/L D-glucose X48 h); metabolic memory group (MG, 30 mmol/L D-glucose x48 h, +5.5 mmol/L D-glouse x48 h); osmotic pressure group (OSM, 5.5 mmol/L D-glucose + 24.5 mmol/L mannitol X48 h). The expressions of Nephrin and α-SMA in podocyte EMT were detected by Western blotting and immunofluorescence. Illumina Hiseq 2000 was applied to characterize the transcriptome profiles of NG, HG and MG groups, DESeq was used to identify the differentially expressed genes (DEGs), gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were implemented for DEGs. The expression levels of the selected DEGs were detected by real-time fluorescence quantitative PCR. Results: Compared with NG group, both Western blotting and immunofluorescence showed that the expression level of Nephrin decreased, while of ct-SMA increased (P0.05). RNA-Seq showed that 194 genes (119 up-regulation and 75 down-regulation) were differentially expressed between HG and NG groups, while 532 genes (316 up-regulation and 216 down-regulation) were differentially expressed between MG and NG groups. Further comparison of the above DEGs showed 108 genes (35 up-regulation and 73 down-regulation) had similar expression patterns in HG and MG groups. The GO enrichment analysis showed 10 GO terms were significantly enriched, and the KEGG pathway enrichment analysis showed TGF-β, focal adhesion plaque, Rap1 and pluripotent regulation of stem cells signal pathways were significantly enriched. PCR showed that the expression levels of Smad9, Snai1 and Mapkapk3 were higher, while of Igf1, Fgf22, Lama1 and Zfhx3 were lower in HG and MG group than in NG group. Conclusions: High glucose can induce podocyte EMT in vitro, and there is a "memory phenomenon" even after normal glucose culture. The occurrence of this phenomenon may be potentially related to TGF-β, focal adhesion plaque, Rap1 and pluripotent regulation of stem cells signal pathways, and upregulation of Smad9, Snai1 and Mapkapk3, as well as downregulation of Igf1, Fgf22, Lama1 and Zfhx3.

Values of Apparent Diffusion Coefficient and Fractional Anisotropy in the Diagnosis of Brucella Spondylitis / 中国医学科学院学报

To compare the differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) between brucella spondylitis (BS) groups at different stages before treatment and the normal control group and to evaluate the change trend of ADC value and FA value at different time points before and after treatment. Totally 53 patients suspected of BS by conventional magnetic resonance imaging (MRI) and later confirmed as BS patients by serological tests were enrolled in this study. These patients underwent conventional MRI and diffusion tensor imaging scans,and the ADC value and FA value were measured. Independent sample test was used to compare the ADC value and FA value between the BS group and the control group,the ADC value and FA value between the BS group at each stage. Repeated measurement ANOV was used to compare the ADC values and FA values at different time points before and after treatment. FA imaging showed that the color code of BS was different from that of the normal control group,and the color code of FA imaging showed increased singal. The ADC values of BS in the acute,subacute,and chronic stages [(1.45±0.02)×10 mm /s,(1.35±0.03)×10 mm /s,(1.26±0.05)×10 mm /s,respectively] were significantly higher than those in the control group [(1.06±0.09) ×10 mm /s](=2.538,=0.009;=1.998,=0.032;=1.575,=0.004),and the FA value (0.55±0.02,0.65±0.03,0.71±0.04,respectively) were significantly lower than those of the control group (0.78±0.02) (=2.440,=0.012; =1.847,=0.041;=2.102,=0.003). Repeated measurement analysis showed that there were statistically significant differences in ADC values and FA values at different time points before and after treatment in the acute,subacute,and chronic stages (ADC:=12.100,<0.001;=8.439,=0.005;=9.704,=0.004,respectively;FA:=7.080,=0.002;=6.607;=0.003;=8.868,=0.001,respectively). The ADC values at different time points after treatment were significantly lower than those before treatment or at a previous time point after treatment (=332.14,<0.001),and the FA values were significantly higher than those before treatment or at a previous time point after treatment (=134.26,<0.001). FA color code can intuitively display differences in BS and normal vertebral bodies and show change of color code before and after treatment. Also,the ADC values and FA values can quantitatively reveal differences between BS and normal vertebral body in different time points and quantify BS vertebral lesion changes before and after treatment. In particular,in BS patients who are recovering from treatment,it can quantify microscopic edema. Therefore,diffusion tensor imaging may be useful objective indicator in evaluating the effectiveness of a specific treatment for BS.

Feasibility of the determination of plasma vardenafil level in rat by performance liquid chromatography-tandem mass spectrometry / 中华心血管病杂志

Objective: To develope and validate a reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of vardenafil concentration in plasma of rat. Methods: Plasma samples of normal Sprague-Dawley rats were collected. A Phenomenex Synergi Polar-RP 80A column (2.0 mm×50 mm, 4 µm) was used. Column temperature was set at 30 ℃. Mobile phase A was 0.1% formic acid in water; mobile phase B was 0.1% formic acid in acetonitrile. The flow rate was 0.4 ml/minutes. Quantitative determination was performed by electrospray ionization, operating in positive ion multiple reaction monitoring (MRM) mode. Cisapride was used as the internal standard. The feasibility of the method was evaluated by examining its specificity, linearity and quantitative range, precision and accuracy, matrix effects, and stability. Results: Under the selected chromatographic and mass spectrometry conditions, the monitoring ions of vardenafil and internal standard were mass-to-charge ratio（m/z) 489.3/151.2 and 466.4/234.2, the retention times of vardenafil and internal standard were 2.62 and 2.80 minutes, respectively, and the peak shape was satisfactory. The method has good linearity in the concentration range of 0.2-200 ng/ml. The intra-batch precision (%CV) and accuracy (%DEV) of vardenafil were 1.5%-9.7% and -6.8%-6.6%, respectively. The inter-batch precision and accuracy of vardenafil were 3.1% -8.4% and -3.7%-4.6%, respectively. In this sample processing method, the extraction recovery rate of vardenafil was obtained at range of 88.2%-104.6%, which met the requirements for the investigation of extraction recovery rate. In this sample processing method, the normalized matrix factor of each quality control concentration of vardenafil was 1.04, 0.85, and 1.04, and the coefficient of variation (%CV) was in the range of 1.7%-10.7%, which met the requirements for the investigation of matrix effects. Variations of short-term stability, long-term stability, and stability of 4 freeze-thaw cycles of vardenafil was within ±15%, and the coefficient of variation were within 5%. Conclusion: The high performance liquid chromatography-tandem mass spectrometry method established in this study is feasible for the measurement of concentration of vardenafil in rat plasma and this method has good specificity and high accuracy, and can be used to detect the concentration of vardenafil in rat plasma.