Identification of taste critical quality attribute and formulation optimization of Xiaoer Qingrening Granules based on electronic tongue and human senses / 药学学报

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

Synthesis and biological activities of three-molecule conjugates with para-aminosalicylic acid as parent nucleus / 药学学报

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

Improvement on Quality Standard of Belladonnae Herba / 中国实验方剂学杂志

ObjectiveTo improve the current standard of Belladonnae Herba in the 2020 edition of Chinese Pharmacopoeia. MethodTaking hyoscyamine sulfate， atropine sulfate and scopoletin as reference substances， and ethyl acetate-methanol-concentrated ammonia（17∶4∶2）as developing solvent， thin layer chromatography （TLC） was applied in the qualitative identification of Belladonnae Herba. The moisture， total ash and ethanol-soluble extract of Belladonnae Herba were determined based on the general principles in the 2020 edition of Chinese Pharmacopoeia （volume Ⅳ）. The contents of hyoscyamine sulfate and scopolamine hydrobromide were analyzed by high performance liquid chromatography （HPLC） with mobile phase of acetonitrile-54 mmol·L-1 phosphate buffer solution （14∶86）， flow rate of 1.0 mL·min-1 and detection wavelength at 210 nm. ResultThe spots in the TLC were clear with good separation and specificity. Hyoscyamine sulfate and scopolamine hydrobromide showed a good linearity with peak area in the range of 0.024 7-0.789 6 g·L-1 （r=0.999 9） and 0.003 9-0.124 0 g·L-1 （r=0.999 9）， the average recoveries of these two ingredients were 100.29% （RSD 1.6%） and 99.04% （RSD 1.4%）， respectively. The limits for moisture， total ash in Belladonnae Herba should be less than 13.0% and the limit for the ethanol-soluble extract should be more than 10.0%. Due to the low content and wide variation of scopolamine hydrobromide， the content of hyoscyamine sulfate should not be less than 0.098%. ConclusionThe established method is simple， specific and reproducible， which can be used to improve the quality control standard of Belladonnae Herba.

Analysis on Chemical Constituents and Dynamic Accumulation of Main Components in Arctium lappa Leaves / 中国实验方剂学杂志

ObjectiveTo determine the chemical constituents of burdock （Arctium lappa） leaves， and elucidate dynamic accumulation rule of four main components， in order to provide the basis for determining the suitable harvest time of burdock leaves. MethodSilica gel， macroporous resin， Sephadex LH-20， octadecylsilane chemically bonded silica （ODS）， microporous resin （MCI） column chromatography and reversed-phase preparative high performance liquid chromatography （HPLC） were used to isolate the main chemical constituents in burdock leaves. Their chemical structures were elucidated by spectroscopic techniques. HPLC-diode array detector （DAD） was used to analyze the dynamic accumulation of four components in burdock leaf. HPLC-DAD was performed on a Shim-pack GIST C18 column （4.6 mm×250 mm， 5 μm） with mobile phase of acetonitrile （A）-0.3% phosphoric acid aqueous solution （B） （0-9 min， 13%A； 9-10 min， 13%-24%A； 10-30 min， 24%A）， flow rate of 1.0 mL·min-1， column temperature of 40 ℃， and detection wavelength at 328 nm. ResultSeventeen compounds were isolated from burdock leaves， and identified as caffeic acid （1）， rutin （2）， kaempferol-3-O-rutinoside （3）， quercetin-3-O-β-D-glucopyranoside （4）， kaempferol-3-O-β-D-glucopyranoside （5）， chlorogenic acid （6）， isochlorogenic acid A （7）， daucosterol （8）， ursolic acid （9）， anemarrhenoside B （10）， （-）-secoisolariciresinol （11）， vladinol D （12）， melitensin （13）， esculetin （14）， 1-（-2-ethylphenyl）-1，2-ethanediol （15）， 1-（-4-ethylphenyl）-1，2-ethanediol （16）， 3-hydroxy-1-（4-hydroxy-3，5-dimethoxyphenyl）-1-propanone （17）. The contents of chlorogenic acid， rutin and kaempferol-3-O-rutinoside in burdock leaves showed an upward trend from April to August， and reached the highest in August. And the content of isochlorogenic acid A firstly increased and then decreased from April to August， and reached the highest in July. ConclusionCompounds 10， 12-17 were isolated from Arctium for the first time. Taking the contents of chlorogenic acid， rutin， kaempferol-3-O-rutinoside， and isochlorogenic acid A as indicators， considering the comprehensive development and utilization of burdock roots and leaves， it is recommended to harvest burdock leaves in mid-August.

Treatment of ankylosing spondylitis with thoracolumbar fractures by robot-assisted internal fixation in lateral decubitus position / 中国骨伤

OBJECTIVE@#To explore the effect of robot-assisted internal fixation in lateral decubitus position for the treatment of ankylosing spondylitis (AS) complicated with thoracolumbar fractures.@*METHODS@#The clinical data of 26 patients with ankylosing spondylitis complicated with thoracolumbar fractures treated from January 2018 to June 2020 was retrospectively analyzed. According to different surgical methods, these patients were divided into observation group and control group. There were 8 patients in observation group, which were treated with robot-assisted percutaneous screw fixation in lateral decubitus position, including 4 males and 4 females, aged form 55 to 85 years old with an mean of (66.25±9.42) years, the course of disease was (4.00±0.76) days on average, 2 cases were T11 fracture, 2 cases were T12, 3 cases were L1 and 1 case was L2. And there were 18 patients in control group, which were treated with conventional percutaneous screw fixation in prone position, including 6 males and 12 females, aged from 48 to 81 years old with a mean of (61.22±9.53) years, the course of disease was (4.11±0.83) days on average, 2 cases were T10 injury, 3 cases were T11, 4 cases were T12, 7 cases were L1, and 2 cases were L2. The intraoperative blood loss, operation time, position time and postoperative neurological complications were compared between two groups. Postoperative visual analogue scale (VAS) at 1d and 3 months, and Oswestry Disability Index (ODI) before and 3 months after operation were observed. According to Gertzbein-Robbins standard to evaluate the accuracy of pedicle screw placement.@*RESULTS@#There was no nerve injury due to pedicle screw placement in both groups. The intraoperative blood loss in observation group and control group was (34.13±4.61) ml and (78.17±22.02) ml, operation time was(92.13±9.82) min and (106.22±11.55) min, position time was(10.00±2.14) min and (15.17±2.66) min, the differences was statistically significant(P<0.05);VAS of the two groups were (2.38±0.52) points and (4.56±0.98) points one day after surgery, respectively, with statistically significant differences (P<0.05), while VAS and ODI three months after surgery showed no statistically significant differences (P>0.05). The screw accuracy was 96.88%(62/64) in observation group and 81.48%(88/108) in control group, the difference was statistically significant(P<0.05).@*CONCLUSION@#Robot-assisted internal fixation in lateral decubitus position for the treatment of ankylosing spondylitis complicated with thoracolumbar fractures can shorten the position time and operation time, significantly improve the accuracy of internal fixation screw placement, relieve the early postoperative pain, reduce intraoperative blood loss and postoperative complications, and facilitate the fast track rehabilitation of patients.

Iridoids of wine-processed Corni Fructus / 中国中药杂志

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7β-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7β-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7β-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).

Three new polyketides from vasR2 gene over-expressed mutant strain of Verrucosispora sp. NS0172 / 中国天然药物

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and

Quality standards of Gleditsiae Spina and its decoction pieces / 中国中药杂志

In view of the current inadequate standards for Gleditsiae Spina in the Chinese Pharmacopoeia, this study put forward some new items of the quality standards of Gleditsiae Spina. Thin-layer chromatography(TLC) was performed for identification with the reference substance of taxifolin and the reference material of Gleditsiae Spina as the control. According to the general principles of the Chinese Pharmacopoeia(2020 edition, Vol. 4), the moisture, total ash content, and alcohol-soluble extract of medicinal materials and decoction pieces of Gleditsiae Spina were determined. The content determination method for medicinal materials and decoction pieces of Gleditsiae Spina was established using high-performance liquid chromatography(HPLC), with taxifolin as the quality control index. Based on the determination results of 30 batches of samples of Gleditsiae Spina from different habitats, the draft quality standards of Gleditsiae Spina were developed, which provided suggestions for the revision of the quality standards of Gleditsiae Spina in the Chinese Pharmacopoeia.

Discovery and activity verification of reniformin A as an anti-tumor leading compound / 中国中药杂志

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive

Associated factors of screened myopia of junior middle school students in six provinces of China / 中国学校卫生

Objective@#To understand the current situation and associated factors of myopia in junior middle school students, and to provide scientific basis for prevention and control of myopia in junior middle school students.@*Methods@#A total of 5 393 junior middle school students were selected from middle schools in Guangdong, Guangxi, Guizhou, Liaoning, Shandong, Shanxi provinces. The visual acuity of middle school students was examined, and the data of general population, economy, sociology and natural environment were obtained through statistical yearbook of each province. The influencing factors of myopia of middle school students were analyzed by univariate and multivariate Logistic regression.@*Results@#The results of single factor analysis showed that the myopia rate of junior high school students was different by gender, grades, parents average wage, sunshine duration, temperature, altitude, longitude and latitude(χ2=47.76，59.05，10.79，106.19，53.56，85.02，76.23，107.07，P<0.05). The results of multi factor analysis showed that gender, grade, average wage, temperature and latitude was positively associated with myopia vision; sunshine duration and longitude were negatively associated with the risk for myopia(OR=1.54，1.34，1.62，7.58，27.10，0.42，0.39，P<0.05).@*Conclusion@#The myopia of junior high school students is affected by a variety of factors, economic and social factors and natural environmental factors have an impact on the screening of sexual myopia in junior high school students. Economic and social factors and natural environmental factors should be taken into account in the formulation of myopia prevention and control measures.

Investigation core emergency response competences of medical staff in public health outbreak of corona virus disease 2019 / 重庆医学

Objective To investigate the core emergency response capabilities of medical workers for corona virus disease 2019 (COVID-19) public health emergency, in order to provide references for improving emergency level. Methods By means of convenient sampling, the general information questionnaire and the medical staff's 2019-new coronavirus (2019-nCoV) core emergency capability questionnaire were used to conduct this survey, and the status of 2019-nCoV core emergency capability of 629 clinical medical staff was analysed. Results The score of core emergency response capability of medical staff for 2019-nCoV was (135.60±21.73)points, with a score rate of 73.3%; the score of preventive capability dimension was (11.69±1.96)points, with a score rate of 77.93%; the score of preparation ability dimension was (20.79±4.18)points, and the score rate was 69.30%; the score of rescue ability was (103.11±16.93)points, with a scoring rate of 73.57%. Conclusion The core emergency response capability of medical worker for 2019-nCoV and its dimensions are at a medium level. At the present stage, the training of core knowledge of medical personnel 2019-nCoV should be strengthened, effective measures should be taken to improve the alleviation of weakness in rescue, and the self-psychological adjustment of medical personnel should be strengthened to improve the core emergency response capability of medical worker.

Impacts of Preoperative Smoking and Smoking Cessation Time on Preoperative Peripheral Blood Inflammatory Indexes and Postoperative Hospitalization Outcome in Male Patients with Lung Cancer and Surgery Treatment / 中国医学科学杂志(英文版)

Objective s To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016. Patients were classified as the current smokers, the never smokers, and the ex-smokers based on their smoking history, and the ex-smokers were allocated into five subgroups according to their smoking cessation times (CeT): CeT≤6 weeks, 6weeks10years. The preoperative peripheral blood white blood cells (WBCs), albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), intraoperative blood loss, 30-day mortality, in-hospital days, hospitalization costs, intensive care unit (ICU), admission days and placement time of closed thoracic drainage tube were compared among different groups.Results There were significant differences in WBC (=5.275, <0.001) and albumin (=2.470, <0.05) among patients of current smokers, ex-smokers with different smoking cessation time, and never-smokers. The blood WBC count in current smokers (7.7×10 /L) was significantly higher than that in ex-smokers (7.0×10 /L)and never-smokers (5.9×10 /L) (=-2.145, <0.05; =-6.073, <0.01, respectively). The level of peripheral blood albumin in current smokers (41.1 g/L) was lower than that in ex-smokers (42.1 g/L) and never-smokers (43.2 g/L) (=2.323, <0.05; =3.995, <0.01, respectively). The level of peripheral blood NLR in current smokers (3.7) was higher than that in ex-smokers (3.1) and never smokers (2.8) (=-1.836, <0.05; =-2.889, <0.01, respectively). There was no significant difference in WBC, albumin and NLR among five subgroups of different smoking cessation time. No significant difference was observed in intraoperative blood loss, 30-day mortality, hospitalization costs, hospital stay, ICU stay and placement time of closed thoracic drainage tube among groups either. Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients. Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes, which may be not impacted by the time length of smoking cessation. Therefore, lung cancer patients should be encouraged to quit smoking at any time.

Analysis of influencing factors of screened myopia in primary school students in seven provinces / 中国学校卫生

Objective@#To understand the current situation and associated factors of myopia among primary school students, and to provide scientific basis for prevention and control of myopia among primary school students.@*Methods@#In Gansu, Guangdong, Guangxi, Guizhou, Liaoning, Shandong, Shanxi and other provinces, 1 prefecture was selected, and a number of primary schools were selected from each region. All the students in the class were selected as the object of this survey. A total of 8 365 middle school students were examined for their eyesight, and the data of general population economic indicators and natural environment indicators were obtained through the statistical yearbook of various provinces and cities. The influencing factors of primary school students myopia were analyzed by chi-square test and multivariate Logistic regression.@*Results@#Univariate analysis showed that different provinces and different sex, different nationalities, different grade, parents average salary, sunshine duration, air temperature, altitude, longitude, latitude, different economic zone(χ2=116.22, 18.08, 26.33, 1 059.04, 14.86, 10.28, 16.95, 10.01, 23.15, 29.43, 88.14, P<0.05). Multivariate analysis results showed that gender, grade, sunshine duration, longitude were risk factor for poor vision(OR=1.31, 1.71, 1.45, 1.54, P<0.05); Economic zone and parents salary were protective factors for poor eyesight of students (OR=0.65, 0.86, P<0.05).@*Conclusion@#Myopia of primary school students is affected by a variety of factors, economic and social factors and natural environmental factors have an impact on the screening.

Shunt products of aminoansamycins from aas1 overexpressed mutant strain of Streptomyces sp. S35 / 中国天然药物

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.

Studies on chemical constituents of Isodon henryi / 中国中药杂志

The chemical constituents of the water extraction of the aerial parts of Isodon henryi were investigated by various chromatographic methods including D-101 macroporous adsorptive resins,silica gel,sephadex LH-20,and semi-preparative HPLC. As a result,ten compounds were separated and purified. By analyses of the UV,IR,MS,NMR spectra,their structures were determined as rabdosinate( 1),lasiokaurin( 2),epinodosinol( 3),rabdosichuanin C( 4),epinodosin( 5),hebeirubescensin k( 6),rubescensin C( 7),enmenol( 8),oridonin( 9),and enmenol-1-β-glucoside( 10). Compounds 1-8 and 10 were isolated from I. henryi for the first time. Compounds 2 and 9 showed inhibitory effects against four tumor cells,with IC50 values of 2. 25-9. 32 μmol·L-1.

Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway / 中华医学杂志(英文版)

Background@#Follistatin-like 1 (FSTL1) is a novel profibrogenic factor that induces pulmonary fibrosis (PF) through the transforming growth factor-beta 1 (TGF-β1)/Smad signaling. Little is known about its effects on PF through the non-Smad signaling, like the mitogen-activated protein kinase (MAPK) pathway. Therefore, this study aimed to investigate the role of FSTL1 in PF through the MAPK signaling pathway and its mechanisms in lung fibrogenesis.@*Methods@#PF was induced in Fstl1and wild-type (WT) C57BL/6 mice with bleomycin. After 14 days, the mice were sacrificed, and lung tissues were stained with hematoxylin and eosin; the hydroxyproline content was measured to confirm PF. The mRNA and protein level of FSTL1 and the change of MAPK phosphorylation were measured by quantitative polymerase chain reaction and Western blotting. The effect of Fstl1 deficiency on fibroblasts differentiation was measured by Western blotting and cell immunofluorescence. MAPK signaling activation was measured by Western blotting in Fstl1 and WT fibroblasts treated with recombinant human FSTL1 protein. We pretreated mouse lung fibroblast cells with inhibitors of the extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) signaling and analyzed their differentiation, proliferation, migration, and invasion by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, and transwell assays. The Student's t-test was used to compare the differences between two groups.@*Results@#Fstl1 deficiency attenuated phosphorylation of the ERK, p38, and JNK signaling in bleomycin-induced fibrotic lung tissue 14 days after injury (0.67 ± 0.05 vs. 1.22 ± 0.03, t = 14.92, P = 0.0001; 0.41 ± 0.01 vs. 1.15 ± 0.07; t = 11.19; P = 0.0004; and 0.41 ± 0.01 vs. 1.07 ± 0.07, t = 8.92, P = 0.0009; respectively), compared with WT lungs at the same time and in primary lung fibroblasts (0.82 ± 0.01 vs. 1.01 ± 0.04, t = 4.06, P = 0.0150; 1.04 ± 0.03 vs. 1.24 ± 0.03, t = 4.44, P = 0.0100; and 0.76 ± 0.05 vs. 0.99 ± 0.05, t = 4.48, P = 0.0100; respectively), compared with TGF-β1-stimulated WT group. Recombinant human FSTL1 protein in lung fibroblasts enhanced TGF-β1-mediated phosphorylation of the ERK (1.19 ± 0.08 vs. 0.55 ± 0.04, t = 6.99, P = 0.0020), p38 (1.18 ± 0.04 vs. 0.66 ± 0.03, t = 11.20, P = 0.0020), and JNK (1.11 ± 0.01 vs. 0.84 ± 0.04, t = 6.53, P = 0.0030), compared with the TGF-β1-stimulated WT group. Fstl1-deficient fibroblasts showed reduced alpha-smooth muscle actin (α-SMA) expression (0.70 ± 0.06 vs. 1.28 ± 0.11, t = 4.65, P = 0.0035, compared with the untreated WT group; 1.40 ± 0.05 vs. 1.76 ± 0.02, t = 6.31, P = 0.0007; compared with the TGF-β1-treated WT group). Compared with the corresponding condition in the control group, the TGF-β1/FSTL1-mediated α-SMA expression was significantly suppressed by pretreatment with an inhibitor of p38 (0.73 ± 0.01 vs. 1.13 ± 0.10, t = 3.92, P = 0.0078) and JNK (0.78 ± 0.03 vs. 1.08 ± 0.06, t = 4.40, P = 0.0046) signaling. The proliferation of mouse lung fibroblast cells (MLgs) significantly decreased after treatment of an inhibitor of p38 (0.30 ± 0.01 vs. 0.46 ± 0.03, t = 4.64, P = 0.0009), JNK (0.30 ± 0.01 vs. 0.49 ± 0.01, t = 12.84, P = 0.0001), and Smad2/3 (0.18 ± 0.02 vs. 0.46 ± 0.02, t = 12.69, P = 0.0001) signaling compared with the dimethylsulfoxide group. The migration and invasion cells of MLgs significantly decreased in medium pretreated with an inhibitor of p38 (70.17 ± 3.28 vs. 116.30 ± 7.11, t = 5.89, P = 0.0042 for the migratory cells; 19.87 ± 0.84 vs. 32.70 ± 0.95, t = 10.14, P = 0.0005 for the invasive cells), JNK (72.30 ± 3.85 vs. 116.30 ± 7.11, t = 5.44, P = 0.0056 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 11.00, P = 0.0004 for the invasive cells), and Smad2/3 (64.76 ± 1.41 vs. 116.30 ± 7.11, t = 7.11, P = 0.0021 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 13.29, P = 0.0002 for the invasive cells) signaling compared with the corresponding condition in the dimethylsulfoxide group.@*Conclusion@#FSTL1 affects lung fibroblast differentiation, proliferation, migration, and invasion through p38 and JNK signaling, and in this way, it might influence the development of PF.

Blocking Two Signals of Immuno-Activated T Cells from Antigen Presenting Cells Can Prevent Chronic GVHD of Murine / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of blocking TCR-CD3 and B7-CD28 signals on immune function of mice with chronic GVHD by using TJU103 and CTLA4-Ig.</p><p><b>METHODS</b>On the basis of foregoing murine model of chronic GVHD, according to interference modes after infusion 6×10 spleen cells of donor mice, the recipients were divided into 5 groups: blank control, cGVHD, TJU103 interference, CTLA4-Ig interference and TJU103+CTLA4-Ig interference groups. The score of clinical manifestation and tissue histopathology were used to evaluate the effects of all the interferences on chronic GVHD.</p><p><b>RESULTS</b>TJU103 and CTLA4-Ig could not influence the formation of the mouse chimera. The analysis of Kaplan survival curve of mice with chronic GVHD showed that the CTLA4-Ig and TJU103+CTLA4-Ig reduced the incidence of chronic GVHD, the TJU103 could delay the occurrence of chronic GVHD, but all the interference factors could not change the severity of chronic GVHD.</p><p><b>CONCLUSION</b>TJU103 can delay the onset time of chronic GVHD, and the CTLA4-Ig can reduce the incidences of cGVHD, the combining use of TJU103 and CTLA4-Ig can significantly reduce the incidence of chronic GVHD, but can not change the severity of chronic GVHD.</p>

Increased Serum Cystatin C in Early Parkinson's Disease with Objective Sleep Disturbances / 中华医学杂志(英文版)

<p><b>Background</b>Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.</p><p><b>Methods</b>We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.</p><p><b>Results</b>The mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO(r = -0.323, -0.315, both P = 0.001) in PD patients.</p><p><b>Conclusions</b>The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.</p>

Death pattern and cause analysis in mice after establishment of the liver alveolar hydatid model / 中国人兽共患病学报

We studied the death pattern and the main causes of death after artificial liver inoculation with alveolar hydatid model,and explored the risk factors and prevention of major complications resulting from death after modeling.The 50 healthy Kunming mice were inoculated with open-staring liver puncture and the physiological changes of the mice were observed dy-namically within 1 5 days after operation.The time and amount of death were recorded,and the causes of death and related fac-tors were analyzed emphatically.On the 1 5 day after surgery,1 9 died;1 died in the ninth day,and the remaining 1 8 died with-in 7 days of the operation.The postoperative death rate began to rise in the second day,and gradually decreased to 1 after the peak of the 4 th and 5 th days.The main causes of death of the mice after inoculation were closely related to the complications of surgical methods,anaesthesia,infection,antigenicity of vesicle,and liver injury.Effective prevention of these complications is the key to improve the survival rate.