Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-serotype community acquired pneumococcal diseases among children in China: A test-negative case-control study.

BACKGROUND: In 2016, China licensed 13-valent pneumococcal conjugate vaccine (PCV13) based on a study that demonstrated its immunogenicity is non-inferior to PCV7. However, the real-world effectiveness of PCV13 against vaccine-serotype pneumococcal diseases in China has limited evidence. METHODS: A test-negative case-control study was conducted among children under 5 years old admitted to the Children's Hospital of Soochow University (SCH) with respiratory tract infections from January 2018 to December 2020. Cases were defined as children from whom the isolates were tested positive for Streptococcus pneumoniae (S. pneumoniae) with serotypes included in PCV13. Two control groups were included, one represented children with isolates positive for S. pneumoniae of non-PCV13 serotypes and the other comprised children who tested negative for S. pneumoniae. The S. pneumoniae-negative controls were selected by matching them to the cases based on gender, age and admission date in a 1:1 ratio. Vaccine effectiveness (VE) was calculated using a logistic regression model as (1- adjusted odds ratio) * 100 %. RESULTS: A total of 2371 pneumococcal isolates were included in the analysis, of which 75.0 % (1779/2371) were covered by PCV13 serotypes. Consequently, these 1779 children were classified as cases, and 592 children were designated as non-PCV13 serotype controls. Another 1779 children were correspondingly recruited as S. pneumoniae-negative controls. Overall, 40 cases (2.3 %) and 148 controls (6.2 %) had received vaccination. The overall VE in the PCV13/non-PCV13 serotypes case-control study was 50.0 % (95 % CI: 15.0, 70.7), which was lower than the VE of 74.4 % (95 % CI: 60.7, 83.3) in the matched PCV13/S. pneumoniae-negative case-control study. VE was higher for ≥ 2 or ≥ 3 doses of vaccination compared to ≥ 1 dose. VE against specific PCV13 serotypes (6B, 6A and 19F) was higher than for other serotypes. CONCLUSIONS: PCV13 vaccination demonstrates effectiveness against vaccine-serotype pneumococcal diseases in children, particularly for serotypes 6B, 6A and 19F.

Treatment of Diabetic Retinopathy with Blood Stasis， Collateral Obstruction， and Qi and Yin Deficiency Syndrome with Tongluo Mingmu Capsules： A Randomized， Double-blind， and Multi-center Phase Ⅲ Clinical Trial / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ2=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ2=17.927， P<0.01）. The disappearance rate of dry eyes （χ2=8.305）， dull complexion （χ2=4.053）， lassitude （χ2=10.267）， shortness of breath （χ2=8.494）， and dry stool （χ2=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ2=8.382）， fundus changes （χ2=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis / 中华内科杂志

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

The Role of PTEN/PI3K/AKT Signaling Pathway in Apoptosis of Liver Cells in Cocks with Manganese Toxicity.

PTEN/PI3K/AKT signaling pathway is an important pathway for cell proliferation and apoptosis. Exposure to excess manganese (Mn) can cause damage in organisms. However, whether Mn toxicity can cause apoptosis is still not clear. In order to explore the mechanism of PTEN/PI3K/AKT signaling pathway responsible for Mn-induced apoptotic injury, 160 Hyline cocks were divided into four groups; there were the control group (Con group), the low-dose Mn group (L group), the medium-dose Mn group (M group), and the high-dose Mn group (H group). The cocks in Con group, L group, M group, and H group were fed with MnCl2 diet containing 100, 600, 900, and 1800 mg/kg, respectively. The growth status of cocks in each group was observed on days 30, 60, and 90. Thirty cocks were randomly selected from each group and sacrificed on day 90 for optical microscope observation and fluorescence microscopic observation, as well as for transcription-level expression of apoptosis-related genes and heat shock proteins (HSPs) in the liver. The results showed that the growth status of cocks was gradually depressed with the extension of feeding time and with the increase of Mn dose. On day 90, the results of optical microscope observation and fluorescence microscope observation showed that damage and apoptosis appeared in the cock liver cells under Mn exposure groups. The results of transcription-level detection of apoptosis-related genes and HSPs indicated that Mn exposure upregulated eleven pro-apoptotic genes (including RIP1, RIP3, MLKL, Bax, Caspase-3, FADD, Cyt-C, ERK, JNK, Caspase-8, and P38) and downregulated one anti-apoptotic gene Bcl-2, further meaning that exposure to Mn-induced apoptosis in cock liver cells and PTEN/PI3K/AKT signaling pathway took part in molecular mechanism of apoptosis caused by excess Mn. Moreover, in our experiment, the increase of four HSPs (including HSP27, HSP40, HSP60, and HSP70) was found after Mn treatment for 90 days, which indicated that Mn stress triggered HSPs and HSPs were involved in molecular mechanism of Mn poisoning in cock livers. In addition, we also found there was upregulated dose-dependent manner in fifteen detected genes and there was downregulated dose-dependent manner in Bcl-2, indicating that the apoptosis caused by Mn poisoning in cock liver cells was dose-dependent.

Intervention Mechanism of Bushen Huoxuetang on Osteoporosis Related to Endocrine Therapy in Breast Cancer Based on PI3K/Akt/HIF-1α Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo predict the underlying mechanism of Bushen Huoxuetang in treating osteoporosis related to endocrine therapy in breast cancer by network pharmacology and to verify the results through in vitro cell model. MethodThe main effective components and targets of Bushen Huoxuetang were screened out through network pharmacology， and the targets of osteoporosis related to endocrine therapy in breast cancer were further obtained. The intersected targets were analyzed by Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Kaplan Meier plotter was used to analyze the survival of crucial targets. Finally， the inhibitory activity against cell proliferation was evaluated by in vitro methye thiazolye telrazlium（MTT） assay. The key targets and pathways were verified by Western blot， and the mRNA expression of the key targets was evaluated by real-time polymerase chain reaction（Real-time PCR）. ResultA total of 716 active components and 249 key targets of Bushen Huoxuetang were obtained from network pharmacology. There were 135 common targets， among which protein kinase B（Akt）1 and hypoxia-inducible factor-1α （HIF-1α） were two key targets. Additionally， 531 biological processes， 62 cellular components， 162 molecular functions， and 145 signaling pathways including breast cancer and endocrine resistance were involved. The key targets were effectively enriched in phosphatidylinositol 3-kinases（PI3K）/Akt and HIF-1 signaling pathways. According to the MTT assay， the cell proliferation rate and cell motility of MCF-7 and T47D cells in the luminal A cell line were reduced by Bushen Huoxuetang treatment （22.5， 45， 90 g·L-1， and 45， 90， 180 g·L-1） for 48 h as compared with the blank group. As revealed by Western blot， MCF-7 cells were treated with Bushen Huoxuetang （0， 15， 60 g·L-1） for 48 h， and the relative expression of p-PI3K， PI3K， p-Akt， Akt， and HIF-1α was decreased in a dose-dependent manner as compared with the blank group （P<0.05， P<0.01）. Real-time PCR was used to detect the mRNA expression of the key target HIF-1α. The results showed that the mRNA expression of HIF-1α in MCF-7 cells was decreased with the increase in the dose （P<0.01）， and the change was in a concentration-dependent manner. ConclusionThe mechanism of Bushen Huoxuetang in the treatment of osteoporosis related to endocrine therapy in breast cancer may be related to the key targets including Akt1 and HIF-1α through the PI3K/Akt/HIF-1α signaling pathway.

Construction of visual prediction model for no reflow phenomenon in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention / 中华急诊医学杂志

Objective:To build a simple, rapid and accurate visual prediction model for identifying the ST-segment elevation myocardial infarction (STEMI) patients with high risk of no reflow during the primary percutaneous coronary intervention (PPCI).Methods:A retrospective study of STEMI patients treated by PPCI in China-Japan Friendship Hospital from January 2018 to June 2019 was performed. The clinical data including sex, age, comorbidities, personal history, Killip classification and laboratory examinations were collected. Whether the patients had no reflow during the PPCI were retrospective observed. Multivariable logistic regression analysis was used to identify risk factors. A nomogram was developed to predict no reflow risk among STEMI patients. C-index and Hosmer-Lemeshow goodness-of-fit test were used to verify the differentiation, consistency and clinical applicability of the model. Internal verification of the model was used by Bootstrap validation.Results:Of the included 280 patients, the prevalence of no flow rate was 30.7%. Killip class Ⅲ or Ⅳ ( OR=3.537, 95% CI: 1.665-7.514, P=0.002), mean platelet volume≥9 fL ( OR=4.003, 95% CI: 1.091-14.689, P=0.037), Glucose ≥7.8 mmol/L ( OR=2.315, 95% CI: 1.318-4.066, P=0.003) and time from symptoms to hospital ( OR=5.594, 95% CI: 2.041-15.328, P=0.002) were the independent risk factors of no flow (all P<0.05). The AUC of ROC curve in the prediction model was 0.731 (95% CI: 0.668-0.795). The calibration curves were close to the standard curve. Conclusions:The visual prediction model constructed in this study can early identify STEMI patients with high risk of no reflow, and may be helpful for physicians to provide prospective pre-treatment before the occurrence of no reflow during PPCI.

The research progress and prospect of anti-inflammatory antibacterial hydrogel applied to chronic wounds in diabetes / 西安交通大学学报(医学版)

Chronic wounds in diabetes mellitus is a common complication of diabetes mellitus with complex pathogenesis and long recovery time. At present, there are many kinds of dressings for chronic wounds in diabetes, among which synthetic dressings have obvious therapeutic advantages. As an emerging biomaterial, hydrogel has obvious advantages over traditional dressings in terms of water absorption, air permeability, biocompatibility, drug loading ability, and continuous controlled drug release, and has attracted much attention in the repair of chronic wounds in diabetes mellitus. Common hydrogels have anti-inflammatory, antibacterial, antioxidant, tissue-promoting, and hypoglycemic effects. This paper systematically summarizes the progress in research on anti-inflammatory and antibacterial hydrogels in chronic diabetic wounds. Among them, according to different anti-inflammatory and antibacterial mechanisms and materials, common anti-inflammatory hydrogels can be divided into hydrogels loaded with anti-inflammatory drugs, hydrogels based on anti-inflammatory materials, and hydrogels loaded with biological components. Hydrogels can be classified into antibiotic-loaded hydrogels, antibacterial material-based hydrogels, and inorganic nanoparticles-loaded hydrogels. Anti-inflammatory and antibacterial hydrogels have achieved certain research results in the treatment of chronic diabetic wounds, but there are still some technical problems waiting for further improvement. Meanwhile, this paper discusses the prospect of the future development of hydrogels applied in chronic diabetic wounds, aiming to provide systematic theoretical support for the treatment of chronic diabetic wounds in the future.

Study on Improvement Effects and Its Mechanism of Guiyuan Decoction Formula Granules on Model Mice with Decreased Ovarian Reserve / 中国药房

OBJECTIVE：To study the improvement eff ects and its mech anism of Guiyuan decoction formula granules （GDFG） on model mice with decreased ovarian reserve （DOR）. METHODS ：Totally 42 female ICR mice whith with normal estrous cycle were randomly divided into control group ，model group ，estradiol valerate group （positive control ，0.15 mg/kg）and GDFG low-dose，medium-dose and high-dose groups （0.75，1.49，2.98 g/kg），with 7 mice in each group. Except for control group ，other groups were given cisplatin （3 mg/kg）intraperitoneally to establish DOR model. After modeling ，administration groups were given relevant medicine intragastrically；model group and control group were given normal saline intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，ELISA assay was used to measure the serum levels of anti-Müllerian hormone （AMH）and follicle-stimulating hormone （FSH）in mice. Histopathological morphology of ovarian was observed by HE staining. Protein distribution of AMH receptor Ⅱ（AMHRⅡ）and Smad 4 in ovarian tissue were observed by immunohistochemistry. Protein expression of AMHR Ⅱ and Smad 4 were detected by Western blot assay. RESULTS ：Compared with control group ，theserum level of AMH ，the expression of AMHR Ⅱ and Smad 4 protein in ovarian tissue in model group were significantly decreased （P＜0.01），while the FSH level in serum was significantly increased （P＜0.01）；follicles were crumpled and lost nucleus ，ovarian interstitial were fibrosis ，luteum were loose ； AMHRⅡ and Smad 4 protein in ovarian tissue were mainly distributed in the follicle membrane and ovarian interstitial. Compared with model group ，the serum level of AMH ，the expression of AMHR Ⅱ and Smad 4 protein in ovarian tissue was increased significantly in GDFG groups （P＜0.01），while the serum level of FSH was decreased significantly （P＜0.05 or P＜0.01）；in ovarian tissue ，follicles at all levels could be found and follicle morphology was improved ，and no obvious nuclear loss and cumulus formation were found ；AMHRⅡ and Smad 4 protein were mainly distributed in the follicular nucleus （except for GDFG high-dose group) and the granular cell membrane （mainly distributed in the sinus follicles of GDFG medium-dose group ）；they were slightly distributed around the mature follicular nucleus or in corpus luteum. CONCLUSIONS ：GDFG can improve ovarian function of DOR model mice. The mechanism may be related with promoting serum level of AMH ，protein expression of AMHR Ⅱ and Smad 4，improving the distribution of AMHR Ⅱ and Smad 4 protein in ovarian granulosa cell membrane and follicular nucleus ， reducing FSH levels.

Association of serum SIRT1 with extent of coronary artery lesion in acute coronary syndrome patients / 中华急诊医学杂志

Objective:To investigate the potential factors influencing the extent of coronary artery lesion in acute coronary syndrome (ACS) patients with an emphasis on the role of serum SIRT1.Methods:We assessed the clinical data from 81 ACS patients admitted to China-Japan Friendship Hospital. Serum SIRT1 was detected by enzyme linked immunosorbent assay (ELISA), and the extent of coronary artery lesion was evaluated by SYNTAX score before revascularization. All the patients were divided into two groups: high SYNTAX score (severe coronary artery lesion, n=38) and low SYNTAX score (moderate coronary artery lesion, n=43), by means of the median of SYNTAX score. Potential factors influencing SYNTAX score were analyzed through multiple linear regression analysis. Results:Compared with the low SYNTAX score group, patients in the high SYNTAX score group had higher serum SIRT1 level [379.38 (490.14) ng/L vs. 242.95 (173.85) ng/L, P<0.001] and frequency of coronary artery disease family history (42.11% vs. 20.93%, P=0.039). There was no statistical difference among other factors between the two groups. Serum SIRT1 was positively correlated with SYNTAX score in ACS patients ( R=0.452, P<0.010). Serum SIRT1 (ln adjusted), age and estimated glomerular filtration rate were independently correlated with SYNTAX score (ln adjusted) in multiple linear regression analysis (Adjusted R2=0.330, P<0.001). Conclusions:For the first time, we discussed the correlation of serum SIRT1 with extent of coronary artery lesion in ACS patients. Cardiologists should pay more attention to high-risk patients in order to improve the prognosis of ACS patients through timely revascularization strategies.

Disruption of OsRhoGDI2 by CRISPR/Cas9 technology leads to semi-dwarf in rice / 生物工程学报

OsRhoGDI2 was isolated as a putative partner of Rho protein family member OsRacD from rice panicles by yeast two-hybrid, but its function remains unknown. In order to identify the function of OsRhoGDI2, OsRhoGDI2 knockout mutants were created by CRISPR/Cas9 technology. The results showed that two different homozygous mutants were obtained in T0 generation, and eight kinds homozygous mutants were identified in T1 generation. Sequence analysis revealed that the base substitution or base deletion occurred near the editing targets of the gene in knockout rice, and it could be expected that the truncated OsRhoGDI2 proteins lacking the RhoGDI conserved domain would be generated. Phenotype analysis showed that the OsRhoGDI2 knockout rice plants were significantly lower than the control plants. Statistical analysis confirmed that the significant decrease of plant height was due to the shortening of the second and third internodes, suggesting that OsRhoGDI2 gene may be related with rice height control.

Effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia?reperfusion in rats: an in vitro experiment / 中华麻醉学杂志

Objective To investigate the effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia?reperfusion(I∕R)in rats. Methods Thirty lungs, which were i?solated from SPF adult male Sprageue?Dawley rats, in which the model of isolated lung perfusion was suc?cessfully established, were divided into 3 groups(n=10 each)using a random number table: sham oper?ation group(S group), I∕R group and dexmedetomidine group(D group). The lungs were subjected to 60 min of ischemia and apnea after 15?min ischemia followed by 75 min of reperfusion and ventilation to estab?lish the model of isolated lung I∕R injury. In group D, the lungs were perfused with K?H solution containing 10 nmol∕L dexmedetomidine for 15 min and then subjected to 60 min of ischemia and apnea followed by ven?tilation and reperfusion with K?H sloution containing 10 nmol∕L dexmedetomidine for 75 min. Airway resist?ance, lung compliance, perfusion flow and partial pressure of arterial oxygen(PaO2)were recorded at 10 min of perfusion(T0)and 15, 45 and 75 min after restoration of perfusion(T1?3). Lung tissues were ob?tained at 75 min after restoration of perfusion for determination of wet∕dry weight ratio(W∕D ratio)and for examination of pathological changes and ultrastructure of lungs. The activity of superoxide dismutase (SOD)and content of malondialdehyde(MDA)in lung tissues were measured by improved pyrogallol au?toxidation method and thiobarbituric acid method, respectively. The expression of β?endorphin and interleu?kin?8(IL?8)in lung tissues was detected by Western blot. Results Compared with group S, the airway resistance was significantly increased, and the lung compliance, perfusion flow and PaO2were decreased during the perfusion restoration period, the W∕D ratio and content of MDA were increased, the activity of SOD was decreased, and the expression of β?endorphin and IL?8 was up?regulated in I∕R and D groups (P<0.05). Compared with group I∕R, the airway resistance was significantly decreased, and the lung compliance, perfusion flow and PaO2were increased during the perfusion restoration period, the W∕D ratio and content of MDA were decreased, the activity of SOD was increased, the expression of β?endorphin and IL?8 was down?regulated(P<0.05), and the pathological changes of lungs were significantly attenuated in group D. Conclusion The mechanism by which dexmedetomidine reduces lung I∕R injury may be related to inhibiting lipid peroxidation and inflammatory response of lung tissues in rats.

Detection S100B, P-Tau and Aβ1-42 proteins in the plasma of rheumatoid arthritis patients with mild cognitive impairment / 中华风湿病学杂志

Objective To investigate the plasma protein concentration of S100B protein,hyperphosphorylated tau protein (P-tau) and β-amyloid (Aβ1-42) of rheumatoid arthritis (RA) patients with mild cognitive impairment (MCI) and to provide a reference for clinical diagnosis and prevention of cognitive dysfunction of RA patients.Methods The subjects were consisted of three groups:RA patients with MCI,RA patients with normal cognitive function (NC) and healthy controls.The Montreal Cognitive Assessment (MoCA)was used to test patients' cognitive function,generalized anxiety disorder scale-7 (GAD-7) scale and 9-item patient health questionnaire-9 (PHQ-9) were used to exclude anxiety and depression of RA patients.The concentration of S100B protein,P-tau protein and Aβ1-42 protein in plasma was detected by enzyme-linked immunosorbent assay (ELISA),and the correlation among the concentration of S100B protein,P-tau protein and MoCA scores was analyzed by Pearson's chi-squared test.Results ① Cognitive scores showed that some RA patients had MCI.② The plasma levels of S100B (F=11.81,P＜0.05),P-tau (F=3.3,P＜0.05) protein in RA patients with MCI were higher than that in NC RA patients and the control group (P＜0.05).③ The clinical index analysis showed that the concentration of C reactive protein (CRP) in RA patients with MCI was higher than that in NC RA patients and healthy control,the difference was statistically significant (t=6.44,P＜0.05).④The levels of plasma P-tau (r=-0.539,P＜0.05),S100B (r=-0.346,P＜0.05),CRP (r=-0.358,P＜0.05) protein were negatively correlated with cognitive scores (P＜0.05).Conclusion CRP,S100B protein and P-tau protein are associated with the pathogenesis of RA patients with MCI.The consequences of plasma concentration test can be com-bined with cognitive assessment questionnaire to provide reference for clinical diagnosis of RA patients with MCI.

Effect of cuecumin on mammalian target of rapamyein signaling pathway during ischemia-reperfusion injury in isolated rat lungs / 中华麻醉学杂志

Objective To evaluate the effect of curcumin on the mammalian target of rapamyein (mTOR) signaling pathway during ischemia-reperfusion (I/R) injury in isolated rat lungs.Methods Sixty-four clean-grade healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (S group),I/R group,low-dose curcumin group (LC group) and high-dose curcumin group (HC group).The rats only received in vitro perfusion without ischemia in S group.Isolated rat lungs were subjected to 60 min of ischemia followed by 75-min reperfusion to establish the lung I/R injury model in I/R group.Curcumin 5 and 10 μmol/L were added to perfusion fluid from the beginning of reperfusion in LC and HC groups,respectively.Airway resistance (Res),lung compliance,perfusion flow (Flow) and pulmonary venous partial pressure of oxygen (PaO2) were recorded at 10 min of first perfusion (T0) and 15,45 and 75 min of reperfusion (T1-3).Wet/dry lung weight ratio (W/D ratio) was measured at the end of reperfusion.The morphological structure and ultrastructure of lung tissues were observed by using a light microscope and a transmission electron microscope,respectively.The expression of mTOR,Tau protein,nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) mRNA in lung tissues was detected by real-time polymerase chain reaction.The expression of mTOR,phosphorylated Tau protein (pS396 Tau protein),NF-κB and TNF-α protein in lung tissues was determined by Western blot.Results Compared with S group,Res at T1-3 and W/D ratio at T3 were significantly increased,lung compliance,Flow and PaO2 were decreased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was up-regulated at T3 in I/R,LC and HC groups (P＜0.05).Compared with I/R group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in LC and HC groups (P＜0.05).Compared with LC group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in HC group (P＜0.05).The microscopic examination showed that the injury to lung tissues was significantly attenuated in LC and HC groups as compared with I/R group.Conclusion The mechanism by which curcumin reduces I/R injury in isolated rat lungs is related to inhibiting mTOR signaling pathway.

Effect of dexmedetomidine on autophagy during ischemia-reperfusion injury in isolated rat lungs / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on autophagy during ischemiareperfusion (I/R) injury in isolated rat lungs.Methods SPF healthy male Sprague-Dawley rats,weighing 250-320 g,were anesthetized with atropine and pentobarbital sodium,and their lungs were excised to establish the isolated lung perfusion model.Thirty lungs in which isolated lung peffusion models were successfully established were divided into 3 groups (n=10 each) by a random number table method:control group (C group),lung I/R group (I/R group) and dexmedetomidine group (DEX group).The isolated rat lungs were continuously perfused for 150 min in C group.After 15 main of perfusion,the isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in I/R group.In DEX group,the isolated lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetomidine.Pulmonary vascular resistance (PVR) and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min of reperfusion.Lung tissues were collected at 75 min of reperfusion for measurement of lung wet weight (W) and dry weight (D) and for examination of morphological changes of lung tissues (with a light microscope) and autophagic vacuoles of lung cells (under an electron microscope).The W/D ratio and lung injury score were calculated.The expression of mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) in lung tissues was detected by Western blot.Results Compared with C group,the PVR,W/D ratio and lung injury score were significantly increased,the expression of LC3 Ⅱ was up-regulated,and PaO2 was decreased in I/R group and DEX group (P＜0.05).Compared with I/R group,the PVR,W/D ratio and lung injury score were significantly decreased,the expression of LC3 Ⅱ was down-regulated,PaO2 was increased,and the expression of mTOR and p-mTOR was up-regulated in DEX group (P＜0.05).A lot of autophagic vacuoles of lung cells were found in I/R group,and a few autophagic vacuoles of lung cells were observed in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated lung I/R injury is related to inhibiting autophagy in rats.

Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo[2, 3-d] pyrimidine derivatives / 中国药科大学学报

A series of 4-phenyl-pyrrolo[2,3-d] pyrimidine derivatives were synthesized through modifying the structure of the lead compound ruxolitinib by molecular hybridization strategy.It was synthesized from pyrimidine-4,6-diol by Vilsmeier-Haack reaction,SNAr reaction,cyclized,dehydration,Suzuki coupling and finally acylated to give 12 new compounds(12a-121).All structures of the synthesized compounds were confirmed by 1H NMR,13C NMR,and HRMS analysis.The biological activities were evaluated in vitro.Their JAK2 inhibitory activities were studied using JAK2 enzymatic and TF1-GMCSF cellular assays.The results indicated that compounds 12b,12e and 12h showed moderate activity.The anti-tumor activities were studied against JAK2-independent A549 cell line by the MTT assay.Results showed that the tide compounds exhibited potent antiproliferative effect on A549,especially compound 12c(IC50 =0.12 μmol/L),suggesting that this series compounds might be promising anti-tumor agents for futher investigation.

Effects of dexmedetomidine on expression of aquaporins 1 and 5 during lung ischemia/reperfusion in rats: an in vitro experiment / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on the expression of aquaporins 1 (AQP1) and AQP5 during lung ischemia/reperfusion (I/R) in rats in an in vitro experiment.Methods SPF healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were used in this study.Forty-five isolated rat lungs in which the model of isolated lung perfusion was successfully established were divided into 3 groups (n=15 each) using a random number table:sham operation group (S group),I/R group and dexmedetomidine group (D group).The isolated rat lungs were continuously perfused for 150 min in group S.After 15 min of perfusion,the isolated rat lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in group I/R.In group D,the isolated rat lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetotnidine.The lung compliance,airway resistance,perfusion flow and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min after restoration of perfusion.Lung tissues were obtained at 75 min after restoration of perfusion for determination of wet/dry weight ratio (W/D ratio) and for examination of the pathological changes and changes in the uhrastructure.The expression of AQP1 and AQP5 protein and mRNA in lung tissues was detected by Western blot and real-time polymerase chain reaction,respectively.Results Compared with S group,the airway resistance was significantly increased and lung compliance,perfusion flow and PaO2 were decreased during reperfusion,and W/D ratio was increased in I/R and D groups (P＜0.05),the expression of AQP1 and AQP5 protein and mRNA in lung tissues was significantly down-regulated in group I/R,and the expression of AQP 1 and AQP5 protein and mRNA in lung tissues was significantly up-regulated in group D (P＜0.05).Compared with I/R group,the airway resistance was significantly decreased and lung compliance,perfusion flow and PaO2 were increased during reperfusion,W/D ratio was decreased,the expression of AQP1 and AQP5 protein and mRNA in lung tissues was up-regulated (P＜0.05),and the pathological changes of lung tissues was significantly attenuated in group D.Conclusion The mechanism by which dexmedetomidine reduces I/R injury may be related to up-regulation of the expression of AQP1 and AQP5 in rats in an in vitro experiment.

High-Pitch Coronary CT Angiography at 70 kVp Adopting a Protocol of Low Injection Speed and Low Volume of Contrast Medium

OBJECTIVE: To evaluate the feasibility and image quality (IQ) of prospectively high-pitch coronary CT angiography (CCTA) with low contrast medium injection rate at 70 kVp. MATERIALS AND METHODS: One hundred and four patients with suspected coronary artery disease (body mass index < 26 kg/m², sinus rhythm and heart rate < 70 beats/min) were prospectively enrolled and randomly divided into two groups. In group A and group B, 28 mL and 40 mL of 370 mgI/mL iodinated contrast media was administrated at a flow rate of 3.5 and 5 mL/s, respectively. CT values, noise, signal-to-noise ratio, contrast-to-noise ratio (CNR) of the proximal segments of coronary arteries and subjective IQ were evaluated. RESULTS: The CT values and noise in group A were significantly lower than those in group B (434–485 Hounsfield units [HU] vs. 772–851 HU, all p < 0.001; 17.8–22.3 vs. 23.3–26.4, all p < 0.005). The CNRs of the right coronary artery and left main artery showed no statistical difference between the two groups (42.1 ± 13.8 vs. 36.8 ± 16.0, p = 0.074; 38.7 ± 10.6 vs. 38.1 ± 17.0, p = 0.819). No statistical difference was observed between the two groups in IQ scores (3.04 ± 0.75 vs. 3.0 ± 0.79, p = 0.526) and diagnostic ratio (96.1% [50/52] vs. 94.2% [49/52], p = 0.647). CONCLUSION: Prospective high-pitch CCTA at 70 kVp with 28 mL of contrast media and injection rate of 3.5 mL/s could provide diagnostic IQ for normal-weight patients with heart rate of < 70 beats/min.

High-Pitch Coronary CT Angiography at 70 kVp Adopting a Protocol of Low Injection Speed and Low Volume of Contrast Medium

OBJECTIVE: To evaluate the feasibility and image quality (IQ) of prospectively high-pitch coronary CT angiography (CCTA) with low contrast medium injection rate at 70 kVp. MATERIALS AND METHODS: One hundred and four patients with suspected coronary artery disease (body mass index < 26 kg/m², sinus rhythm and heart rate < 70 beats/min) were prospectively enrolled and randomly divided into two groups. In group A and group B, 28 mL and 40 mL of 370 mgI/mL iodinated contrast media was administrated at a flow rate of 3.5 and 5 mL/s, respectively. CT values, noise, signal-to-noise ratio, contrast-to-noise ratio (CNR) of the proximal segments of coronary arteries and subjective IQ were evaluated. RESULTS: The CT values and noise in group A were significantly lower than those in group B (434–485 Hounsfield units [HU] vs. 772–851 HU, all p < 0.001; 17.8–22.3 vs. 23.3–26.4, all p < 0.005). The CNRs of the right coronary artery and left main artery showed no statistical difference between the two groups (42.1 ± 13.8 vs. 36.8 ± 16.0, p = 0.074; 38.7 ± 10.6 vs. 38.1 ± 17.0, p = 0.819). No statistical difference was observed between the two groups in IQ scores (3.04 ± 0.75 vs. 3.0 ± 0.79, p = 0.526) and diagnostic ratio (96.1% [50/52] vs. 94.2% [49/52], p = 0.647). CONCLUSION: Prospective high-pitch CCTA at 70 kVp with 28 mL of contrast media and injection rate of 3.5 mL/s could provide diagnostic IQ for normal-weight patients with heart rate of < 70 beats/min.

Analysis of Antipsychotic Drugs Prescriptions in Outpatient and Emergency Department of Our Hospital dur-ing 2013-2014 / 中国药房

OBJECTIVE:To provide reference for rational use of drugs in patients with mental disorders. METHODS:In retro-spective investigation,47 386 prescriptions of psychiatric department in our hospital during Sept. 2013 to Aug. 2014 were analyzed statistically. RESULTS:Totally 39 496 cases were enrolled in the 47 386 prescriptions. The median age of patients was 31.42,with male to female ratio of 1:1.07;they were diagnosed as schizophrenia and other mental disorder,accounting for 65.34%,and fol-lowed by mood disorders,accounting for 15.20% . They were mainly given single drug and two-drug use,accounting for 30.80%and 61.68%respectively. Clozapine,quetiapine,risperidone were top 3 prescription drugs in the list of frequency;olanzapine,que-tiapine,risperidone were top 3 drug in the list of consumption sum. Among top 20 psychiatric prescription drugs,there were 7 kinds of drugs for schizophrenia and other psychiatric disorders,3 kinds of drugs for mood disorders. CONCLUSIONS:The use of antipsychotic drugs in our hospital is rational basically.

Clinical Observations on the Therapeutic Effect of Long Snake Moxibustion on Different Types of Lumbago / 上海针灸杂志

ObjectiveTo investigate the therapeutic effect of long snake moxibustion on different types of lumbago.Method Patients with lumbago of kidney deficiency, dampness-heat, blood stasis or cold-dampness type were enrolled, 30 cases each. Pre-treatment lumbago scores, post-treatment lumbago scores and clinical therapeutic effects were compared. Statistical analysis was carried out.ResultA marked therapeutic effect was produced in every group of patients after two courses of treatment. The total efficacy rate was 93.3% in lumbago of kidney deficiency type, 86.7% in lumbago of dampness-heat type, 90.0% in lumbago of blood stasis type and 96.7% in lumbago of cold-dampness type; there was no statistically significant difference (P>0.05). There was a statistically significant post-treatment difference in the pain score between the groups of patients (P<0.05).ConclusionLong snake moxibustion has a very good therapeutic effect on every type of lumbago. The therapeutic effect is best in patients with lumbago of cold-dampness type.