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@#Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.
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OBJECTIVES@#High fat-induced podocyte injury is one of the important factors leading to obesity related nephropathy (ORG), but the mechanism is not clear. This study aims to explore the mechanism of period circadian clock 3 (PER3) in the oxidative stress and inflammation induced by palmitic acid (PA) in podocytes.@*METHODS@#The C57BL/6J mice were fed with chow and high-fat diet for 16 weeks. The PER3 expression in kidney tissues were detected in the normal body weight group and the obesity group. The PER3 mRNA and protein expression were detected after the podocytes were induced with different concentrations (0, 50, 150 and 300 μmol/L) of PA for 48 h. The PER3 mRNA and protein expression were detected after the podocytes were induced with 150 μmol/L PA for 0, 24, 36, and 48 h. Triglyceride (TG) levels were examined in the PA group, the adenovirus (ad)-PER3+PA group, and the siRNA-PER+PA group after the podocytes were transfected by Ad-PER3 or small interfering RNA (siRNA)-PER3 for 48 h and subsequently were induced with 150 μmol/L PA for 48 h. The differential gene expression was detected using RNA sequencing (RNA-seq) after podocytes were transfected by siRNA-PER3 (siRNA-PER3 group) and siRNA-control (siRNA-control group), respectively. The mRNA levels of nephrin, podocin, podocalyxin, podoplanin, superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), catalase (CAT), and the levels of malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-2 (IL-2) were detected after podocytes were transfected with Ad-PER3 or Ad-control for 48 h and then they were induced by 150 μmol/L PA for 48 h.@*RESULTS@#The PER3 was down-regulated in the obesity group compared with the normal body weight group (@*CONCLUSIONS@#PER3 can decrease the PA-induced oxidative stress and inflammatory factor secretion via inhibiting the lipogenesis in podocytes.
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Animals , Mice , Circadian Clocks , Mice, Inbred C57BL , Oxidative Stress , Palmitic Acid/toxicity , Podocytes/metabolismABSTRACT
Objective:To analyze the current situation and characteristics of online public sentiments faced by public hospitals since the outbreak of COVID-19, and provide suggestions for coping strategies for such hospitals.Methods:The data of " trending topic" or " Trending hash tag" of " Wuhan Union Hospital" and " anti-epidemic" were captured on three mainstream new media platforms, namely Sina Microblog, Tik Tok and Headline Today with the help of data analysis tools of Sina and online data statistical software from December 2019 to February 2020. Content analysis method was used to analyze the occurrence frequency, time distribution and development trend of public sentiment on Internet.Results:Under the epidemic of COVID-19, public hospitals faced an exponential growth of online public sentiment. The cumulative total number of searches was 72 119 802 tens of thousands of that before the epidemic. The transmission showed fragmentation of content, instantaneous speed and higher attention to negative information, which brought great challenges for public hospitals.Conclusions:The high participation of online discussion of COVID-19 is unprecedented. Thus public hospitals should attach importance to the work related to online public sentiment, and establish corresponding coping mechanism for response.
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Objective@#To investigate the inhibitory effect of bortezomib (PS-341) on enterovirus replication.@*Methods@#The methyl thiazolyl tetrazolium (MTT) assay was used to value cell viability in response to PS-341 treatment. The protein and viral gene mRNAs were measured by real-time quantitative PCR (qRT-PCR).@*Results@#Our result show that after enterovirus (EV)-D68 or coxsackievirus B3 (CV-B3) infected cells were treated with PS-341, compared with the control group, the inhibition rate of the intracellular viral RNA reached 50%~70% or 60%~90%. PS-341 was added after RD cells were infectd with EV-D68, the intracellular virus titer was down-regulated by 90.23% and 83.40% in the supernatant, the intracellular virus titer was down-regulated by 93% and 90% in the supernatant and in RD cells. PS-341 had no effect on virus adsorption and importing. The cells were treated with PS-341 and apoptosis-inhibiting agent Ac-YVAD-CHO, the viral RNA replication inhibition rate reached 10%-30%, and the expression of viral protein was increased, which indicated that the inhibitory effect of PS-341 on viral replication was attenuated.@*Conclusions@#According to the result of the study, PS-341 could reduce apoptosis by regulating the proteasome pathway, inhibiting the gene replication and assemble, without effect on virus adsorption, entry and release. In addition, PS-341 also inhibited the replication of CV-B3 in cells, which suggest that PS-341 has a broad spectrum anti-EVs effects.
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Objective@#To investigate the effect of microRNA-26a-5p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSC) and its related mechanisms.@*Methods@#hPDLSC in periodontal tissues from healthy adults and hPDLSC from periodontitis patients (PPDLSC) were isolated and cultured in vitro, respectively. The PPDLSC were divided into Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups. Group Ⅰ is control group, and the other four groups were transiently transfected with miR-NC, miR-26a-5p, antimiR-NC and antimiR-26a-5p lentiviral vectors, respectively. The osteogenic differentiation abilities of the cells in vitro were determined by alizarin red staining, alkaline phosphatase (ALP) activity assay and real-time quantitative PCR (qPCR). Totally 40 male mice (6-weeks) were equally divided into five groups with 8 mice in each group. The PPDLSCs cells (1×107/ml) in Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups, which adhered to hydroxyapatine-tricalcium phosphate (HA-TCP), were implanted into the nude mice subcutaneously and the animal models were constructed to analyze the effect of miR-26a-5p on the osteogenic differentiation of PPDLSCs in vivo. PPDLSCs were divided into A, B, C, D groups, and transfected with miR-26a-5p+Wnt5a-Wt, miR-NC+Wnt5a-Wt, miR-26a-5p+Wnt5a-Mut and miR-NC+Wnt5a-Mut in each of the above mentioned 5 groups, respectively. The luciferase activity assay was used to detect the relative luciferase in A, B, C and D groups to analyze the targeting relationship between miR-26a-5p and Wnt5a. Osteogenic differentiation related proteins expression were analyzed by western blotting.@*Results@#hPDLSC and PPDLSC were observed consistent with the characteristics of mesenchymal stem cells and had osteogenic differentiation ability in vitro. Compared with hPDLSC [(89.87±8.12)%], the osteogenic capacity of PPDLSC [(31.46±6.56)%] was significantly lower (P<0.05). The ALP activity (1.88±0.59), calcified nodules (79.88±5.92), the expression of the osteogenic differentiation markers Runt-related transcription factor 2 (Runx2) (2.40±0.70), ALP (2.10±0.60) and osteocalcin (3.00±0.90) mRNA in the PPDLSC from Group Ⅲ were significantly higher in comparison with the control group [(0.88±0.34), (29.69±2.65), (1.30±0.30), (0.09±0.25), (1.71±0.50)], while those from Group Ⅴ[(0.44±0.07), (14.83±3.05), (0.50±0.11), (0.30±0.08) and (0.80±0.17)] were significantly lower (P<0.05). In vivo studies in nude mice showed that the proportion of the osteogenic region [(34.96±5.65)%] in the miR-26a-5p group was significantly increased in comparison with the control group [(23.28±3.03)%], while in the antimiR-26a-5p group [(8.02±2.27)%] was significantly lower (P<0.05). The luciferase activity of the Group A (0.46±0.06) was significantly lower than Group B (3.46±0.45) (P<0.05). Compared with the control group, the expression levels of Wnt5a protein, calmodulin kinase Ⅱ and protein kinase C proteins in the Group Ⅲ were significantly decreased, while those in the GroupⅤ were significantly increased (P<0.05).@*Conclusions@#MicroRNA-26a-5p could promote osteogenic differentiation of PPDLSC in vivo and in vitro, and its mechanism might be inhibiting the activation of Wnt/Ca2+ signaling pathway by targeting Wnt5a.
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Objective To compare the therapeutic efficacy of plasmapheresis (PP ) and intravenous immunoglobulin (IVIG) plus Rituximab for antibody-mediated rejection (AMR) after kidney transplantation .Methods From May 2015 to November 2018 ,a single-center retrospective cohort study was conducted for 540 recipients with high-resolution HLA undergoing kidney transplantation .According to the criteria of diagnosing AMR and patient selection ,20 patients were selected for PP+IVIG (group A ,n=12) ,PP+ IVIG+ Rituximab (group B ,n=8) .The efficacies and outcomes of two groups were compared .Results During a follow-up period of (12 .0 ± 5 .8 ) months ,no significant inter-group differences existed in basic profiles (P> 0 .05) .After AMR treatment ,serum creatinine levels decreased significantly from 283 .4 to 226 .4 μmol/L in group A (P=0 .001) and from 289 .4 to 166 .6 μmol/L in group B (P=0 .049) .And the magnitude of decline was more marked in group B (P=0 .023) .Meanwhile ,antibody MFI (log10) decreased from 3 .73 to 3 .62 in group A (P=0 .012) and from 3 .57 to 3 .02 in group B (P=0 .043) .At months 3 and 6 , serum creatinine level was lower in group B than that in group A (125 .0 vs .166 .1 μmol/L , P=0 .03 ;127 .0 vs .169 .0μmol/L ,P=0 .048) .The serum creatinine levels of AMR patients were 249 .8 and 233 .8 μmol/L respectively ( P= 0 .182 ) .Serum creatinine levels were 176 .1 and 120 .3 μmol/L ( P=0 .045) and 180 .2 and 114 .8 μmol/L at months 3 and 6 (P=0 .044) respectively .Serum creatinine levels were 202 .8 and 122 .5μmol/L (P=0 .049) in group A and 142 .7 and 107 .0μmol/L (P=0 .046) in group B respectively .Four recipients developed allograft failure .At month 6 post-operation ,AMR occurred in group A (n=3 ,25％ ) and group B (n=1 ,12 .5％ ) .And the incidence of leucopenia was 37 .5％ and 0 (P=0 .049) in groups A and B respectively .Conclusions PP and IVIG plus rituximab is more efficacious for AMR .The earlier occurring time ,the better prognosis .
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As countries two-child policy implementation of our country, neonatal birth rate greatly increases, and elderly parturient women , high risk factors of pregnant mothers and newborns increase. Newborns hospitalized rate rises, among which the relevant (premature and low birth weight) of neonatal infection, especially bacterial infectious diseases increases. Clinical signs and symptoms of neonatal infections is not obvious. If further developes, infections could cause neonatal sepsis systemic inflammatory response and even endanger life. Pediatrician should concern with some relevant inspections about newborns infection, in order to find early disease, treat early treatment, and reasonable application of apply antibiotics reasonably.
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Objective To explore the relationship between platelet to lymphocyte ratio(PLR) and the severity of renal impairment in elderly patients with type 2 diabetes mellitus (T2DM) Methods Two hundred elderly T2DM patients treated in our department of endocrinology from January 2017 to January 2018 included 100 cases with diabetic nephropathy(DN group)and 100 without nephropathy(control DM group),and 100 individuals undergoing physical healthy examination during the same period(normal control group)were retrospectively enrolled.DN group included 50 early,27 medium and 23 end stage patients.Albumin to globulin ratio (A/G),hemoglobin A1c (HbA1c),urea nitrogen (BUN),serum creatinine (Scr),estimated glomerular filtration rate (eGFR),24-hour urine protein quantification (24h-UTP),neutrophil-lymphocyte ratio (NLR),plateletlymphocyte ratio(PLR),etc.were collected and compared among DN group,control DM group and normal control group.Binary Logistic regression analyses were performed to predict whether elderly patients with T2DM progress to DN.Correlations between PLR and HbA1c were analyzed using Spearman correlation coefficient.Results The BMI,waist circumference,waist-hip ratio,systolic blood pressure,disease duration,A/G,Scr,BUN,eGFR,24 h-UTP,interleukin 6 (IL-6),hypersensitive C-reactive protein(hs-CRP),PLR,and NLR showed statistically significant differences among three groups(all P ＜ 0.05).The differences in A/G,Scr,BUN,eGFR,24h-UTP,hs-CRP,PLR,and NLR between early,medium and end phases of DN were statistically significant (all P ＜ 0.05).The predictors for the progression to diabetic nephropathy were the levels of A/G(OR:1.12,95％CI:0.89-1.65),Scr(OR:200.34,95％CI:65.28-412.36),BUN(OR:10.26,95％CI:8.34-16.94),eGFR (OR:85.37,95 ％ CI:78.31-103.57),24h-UTP (OR:187.32,95 ％ CI:142.92-1523.49),PLR (OR:81.51,95％CI:78.45-132.68),NLR(OR:1.20,95％CI:1.07-3.57),IL-6(OR:4.25,95％CI:3.76-9.31),and hs-CRP (OR:3.41,95％ CI:2.35-10.51) in T2DM patients.There were significant correlations of PLR with A/G,Scr,BUN,eGFR,24 UTP,NLR,IL-6,and hs-CRP (r =-0.338,0.469,0.521,-0.457,0.463,0.642,0.297,0.448,all P＜0.05).Conclusions PLR,which is inexpensive and easy to measure,can predict the risk of progressing to DN in elderly T2DM patients and may evaluate their renal function,and is worth extending in clinical practice.
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Hydrogen peroxide, an important antimicrobial agent in oral cavity, plays a significant role in the balance of oral microecology. At the early stage of biofilm formation, about 80% of the detected initial colonizers belong to the genus Streptococcus. These oral streptococci use different oxidase to produce hydrogen peroxide. Recent studies showed that the produced hydrogen peroxide plays a critical role in modulating oral microecology. Hydrogen peroxide modulates biofilm development attributed to its growth inhibitory nature. Hydrogen peroxide production is closely associated with extracellular DNA(eDNA) release from microbe and the development of its competent cell which are critical for biofilm development and also serves as source for horizontal gene transfer. Microbe also can reduce the damage to themselves through several detoxification mechanisms. Moreover, hydrogen peroxide is also involved in the regulation of interactions between oral microorganisms and host. Taken together, hydrogen peroxide is an imperative ecological factor that contributes to the microbial equilibrium in the oral cavity. Here we will give a brief review of both the origin and the function in the oral microecology balance of hydrogen peroxide.
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Biofilms , Hydrogen Peroxide , Mouth , StreptococcusABSTRACT
Objective To construct an animal model of vascularized iliac bone transplantation which could establish the immune chimerism.Methods The experiment was divided into three groups.In experiment group we slected the male SD rats as donors and the female SD rats as recipients.Then the experiment group was performed the improved vascularized ilium transplantation operation.The positive group was male SD rats without handling.The negative group was female SD rats without handling.On the twenty-eighth day after surgery, the rat SRY gene was detected by PCR.Dynamically monitoring the changes of the ratio of CD4+/CD8+ T cells by flow cytometry after operation.Dynamically monitoring the changes of the levels of serum IL-2 by enzyme linked immunosorbent assay after operation.Imaging and pathology were used to detect the transplanted iliac bone.Results Ten transplantations were performed in the experiment group and 7 flaps survived with a successful rate of 73 ％.SRY gene was detected in female rats that receive the male rats'iliac bone transplantation by PCR in the experiment group.After Micro-CT scanning and three-dimensional reconstruction, it showed that the transplanted iliac bone mineral density was decreased.Comparing rats that establish the chimerism with normal rats, the ratio of CD4 +/CD8 + T cells and the levels of serum IL-2 had no difference.Pathological results showed that the transplanted iliac bone of rats with chimerism were normal and the rats without chimerism were necrotic.Conclusions From the improved vascularized ilium transplantation operation, we successfully detected the SRY gene in female rats which received the male rats' iliac bone transplantation.It proved that the improved vascularized ilium transplantation operation could establish the chimerism.Through the immunosuppressant, the immune status of the rat after operation was well.
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Objective To study the nurse-patient communication procedures among nursing interns. Method Totally 334 nursing interns were involved in the survey using the basic questionnaire and the nurse-patient communication procedure scale. Result The average score of the communication skills was 22 . 91 ± 2 . 13 , with the dimensions of communication preparation (0.97 ± 0.07), information collection (0.88 ± 0.13), information sending (0.90 ± 0.12), respecting patients (0.91 ± 0.18), ending communication (0.98 ± 0.08). Conclusions The nurse-patient communication skills of the nursing interns were at a relatively high level. They could conduct the effective communication according to the communication procedures in the sequence of communication preparation, information collection, information sending, respect patients and ending communication. But they are weak in the procedures of information collection and information sending. Therefore, some special trains, such as case analysis, can be done to improve the ability in these procedures.
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Background Small incision cataract surgery combined with intraocular lens (IOL) implantation remains a popular way for cataract.However,some factors affect the postsurgical visual outcomes and lower the patients' satisfaction,including intraoperative and postoperative complications as well as corneal refractive and thickness changes.Objective This study was to evaluate the influence of corneal refractive and thickness changes on visual fluctuation after 2.6 mm temporal incision surgery for cataract.Methods A series cases-observational study was designed.Twenty-nine eyes of 25 age-related cataract patients received 2.6 mm temporal transparent incision phacoemulsification and IOL implantation from November,2011 through April,2012 in Eye & ENT Hospital of Fudan University under the informed consent.The uncorrected visual acuity (UCVA),best corrected visual acuity (BCVA),automatic and subjective refraction were examined,and the central corneal thickness (CCT) and corneal vector astigmatism were measured using Pentacam analysis system before and after operation.The examination outcomes were compared among different time points,and the influencing factors of UCVA or BCVA were analyzed.Results The mean UCVA (LogMAR) was 0.52±0.06 in 1 day and 0.64±0.07 in 2 months after surgery,with a significant difference between them (t=-3.051,P＜0.05).The mean BCVA (LogMAR) was 0.24±0.04 and 0.13± 0.04 in postoperative 1 day and 2 months,showing a significant difference between them (t =-3.031,P＜0.05).Spherical equivalents (SE) were (-1.74±0.28) D,(-1.99±0.27) D and (-1.69±0.24) D in postoperative 1 day,14 days and 60 days,respectively,with a significant difference among the 3 time points (F =3.562,P =0.039),and significant difference also was found between postoperative 1 day and 14 days (t =2.515,P＜0.05) or between postoperative 14 days and 60 days (t =-2.987,P ＜ 0.05).The preoperative J0 value was (0.06 ± 0.06) D,and postoperative J0 value was (0.29±0.08) D on the first day,which was significant higher than that in preoperation (t =-4.625,P＜0.01).In addition,J0 value showed a significant difference between postoperative 1 day and 14 days (t=-7.858,P＜0.01) as well as between postoperative 14 days and 2 months ([0.38±0.07] D versus [0.27±0.07] D,t=-5.649,P＜0.01).The mean CCT was (547.1±25.3) μm,(599.4±56.9) μm,(557.0±27.1) μm and (551.0 ± 25.9) μm before and 1 day,14 and 60 days after operation,with significant differences among the various time points (F =9.792,P ＜ 0.001),and significant differences also were seen in the CCT between preoperation and postoperative 1 day (t =-5.116,P＜0.01),between postoperative 1 day and 14 days (t =4.135,P＜ 0.01),between postoperative 14 days and 60 days (t=2.082,P＜0.05).UCVA=0.513-1.183×C J45(F=16.724;t=-4.089,P=0.026) and BCVA=-1.314+0.003×CCT (F=22.322;t=4.725,P=0.018).Conclusions The UCVA remains a downward trend,and BCVA sustains upward trend after 2.6 mm temporal transparent incision phacoemulsification combined with IOL implantation surgery.Postoperative UCVA is affected by corneal astigmatism change,while BCVA is influenced by CCT change.
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Racemization is probably the most abundant post-translational modification (PTM) in aged lens.According to previous studies,L-amino acid in α,β and γ crystallins are tend to transfer into D-amino acid with aging,leading to a series of age-related changes in the structure,metabolism and function of lens.Aggregated highmolecular-weight proteins gradually accumulate in both nuclear and cortex region,which will have a negative effect on the function of crystallins and finally lead to capacity of lens.Moreover,it is likely that racemization of crystallins eventually leads to cataract formation and development as well.The material effect and mechanism of racemization changes in human age-related lens still requires further research.