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Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.
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Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.
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Male , Female , Child , Humans , Infant , Child, Preschool , Posterior Leukoencephalopathy Syndrome/complications , Seizures/etiology , Brain Diseases/diagnostic imaging , Status Epilepticus , Seizures, Febrile/diagnostic imagingABSTRACT
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
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Humans , Antiviral Agents/chemistry , COVID-19 , COVID-19 Drug Treatment , High-Throughput Screening Assays , Molecular Docking Simulation , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural ProteinsABSTRACT
italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.
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Objective To explore the clinical pharmacist participation in the treatment of pregnancy complicated with Clostridium difficile infection. Methods From the perspective of medications, clinical pharmacists followed evidence-based medical practice, combined pharmaceutical theory with clinical evidence and provided individualized pharmacy care in drug selection, dose adjustment, medication regime and liver protection treatment. Results Clinical pharmacists integrated into the treatment team to ensure the effectiveness and safety of medication in the patient with pregnancy. Conclusion The individualized pharmacy care improved the effectiveness of drug treatment.
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OBJECTIVE@#To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT.@*RESULTS@#The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment(P<0.01); the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ(P<0.01). The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD(P<0.05).@*CONCLUSION@#ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.
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Humans , Blood Proteins , Chronic Disease , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , rho-Associated KinasesABSTRACT
OBJECTIVE@#To assess the efficacy and safety of Chinese medicine injection (CMI) for treating acute lung injury/acute respiratory distress syndrome (ALI/ARDS).@*METHODS@#Randomized controlled trials (RCTs) were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019. The Cochrane Handbook was used to evaluate risk of bias in the included studies. Data analysis was conducted using RevMan 5.3.3 software.@*RESULTS@#A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis. The main meta-analysis showed that CMI combined with conventional therapy (CT) was more effective than CT alone in reducing the acute physiology and chronic health evaluation (APACHE) H score [mean difference (MD): -1.74 points, 95% confidence interval (CI): -2.77 to -0.71, I@*CONCLUSIONS@#CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS. However, we could not make a definite conclusion due to low quality of included studies and uncertain security. Future studies should focus on improving research design, especially in blindness and placebo. The reporting of adverse events was also needed.
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Objective To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods Twenty-two patients were collected in the Department of Pediatrics,Peking University First Hospital from April 2007 to July 2016. The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 muta﹣tion was identified by the targeted next generation sequencing. Results Twenty-two de noνo KCNQ2 missense muta﹣tions from 22 patients with neonatal/infantile epileptic disorders were found. These patients had an onset of epilepsy in early infancy(median age:2 days). The seizure type of the first onset was mainly focal seizure. Atypical absence epi﹣lepsy,a novel phenotype of KCNQ2 mutation-induced epilepsies was found. The mortality of these patients was high,as 5 patients of the 22 patients died in the follow-up period,4 of which might result from sudden unexpected death in epi﹣lepsy. In the 22 patients,8 patients with anti-epileptic monotherapy became seizure-free. Of the 8 patients with a monotherapy,3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2-related epileptic disorders. These patients have high mortality. Valproate acid is the potentially effective monotherapy for these patients.
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Objective@#To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation.@*Methods@#Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.@*Results@#Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed.@*Conclusions@#This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.
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OBJECTIVE: To explore the working mode of clinical pharmacists involved in postoperative patient-controlled analgesia pump management and its effectiveness. METHODS: According to the postoperative analgesia pump workflow and pharmaceutical monitoring route, SPS22.0 software was used to analyze the data of patients undergoing elective surgery in the Department of Spinal Surgery and General Surgery of Nanjing Drum Tower Hospital from January 2014 to December 2018. RESULTS: The patient-controlled analgesia(PCA) usage rate in spine surgery and general surgery increased. The postoperative pain control compliance rate remained above 90%, and the incidence of adverse reactions decreased year by year. CONCLUSION: Since the clinical pharmacists participated in the management of analgesic pumps, the pharmaceutical monitoring of patient-controlled analgesia pumps has improved the quality of postoperative pain management, enabling patients to receive reasonable, economical and safe drug treatment.
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Objective:To observe the effect of clinical pharmacists on the pain education in the patients with fracture. Methods:A total of 122 fracture patients with ASAⅠ/Ⅱaged 18-80 years were randomly divided into the intervention group (n=61) and the control group(n=61). The control group received the conventional orthopedic treatment..Flurbiprofen was injected for the postopera-tive analgesia,and if the pain VAS score was above 6,pethidine solution was given at the dose of 50 mg immediately. Based on the conventional treatment,the patients in the intervention group were educated by clinical pharmacist one day before the surgery,and then strengthened education was given after the surgery.The pain VAS score,and sleeping quality at 6h,24h,48h and 72h and satisfaction of pain management were compared between the groups.Results:The VAS score of the intervention group was significantly lower than that of the control group at 6 h,24 h,48 h and 72 h after the operation (P<0.05). The scores of sleeping quality in the intervention group at 6 h and 24 h after the operation were higher than those in the control group (P<0.05). The scores of patients' satisfaction were significantly higher in the intervention group than those of the control group (P<0.05). Conclusion: The clinical pharmacist's pain education can improve the degree of pain control and sleeping quality,increase the patients' satisfaction with pain control to a cer-tain extent.
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Objectives To provide genetic counseling and prenatal molecular diagnosis for two families with megalencephalic leukoencephalopathy with subcortical cysts (MLC).Methods Two MLC patients (probands 1 and 2) were admitted to the Department of Pediatrics of Peking University First Hospital in June 2011 and June 2009,respectively.Peripheral blood was collected and DNA sequencing was performed for genetic analysis for the two MLC patients and their parents.Amniotic fluid and villus of two fetuses (fetus 1 and 2) were collected at 21+4 and 12+3 weeks of gestational age from their mothers when they were pregnant again.The genomic DNA of the two fetuses was extracted and corresponding sites of MLC1 gene were sequenced.Haplotype analysis using a combination of 3 microsatellite markers (AR,DXS6807 and DXS6797) on chromosome X and sex determining region of Y chromosome was performed to detect maternal cell contamination.Verification of the prenatal molecular diagnosis and follow up study after birth were conducted for both fetuses.Results Macrocephaly,motor development delay and typical findings on brain MRI were identified in the two probands,and were clinically diagnosed with MLC.Compound heterozygous mutations were detected in proband 1 [c.353C>T (p.T118M) and c.803C>G (p.T268R)] and proband 2 [c.353C>T (p.T118M) and c.836T>C(p.L279P)],respectively.MLC was genetically diagnosed.Heterozygous variation in c.353[c.353C>T (p.T118M)] and wild c.803C were identified in fetus 1,and both wild c.353C and c.836T were found in fetus 2.No maternal cell contamination was detected in both fetuses.Sequencing the corresponding sites after birth confirmed the prenatal diagnosis,and the head circumference and motor development were normal in fetus 1 at 5 months old.No macrocephaly was found and no DNA sequencing was done in fetus 2 at one month old.Conclusions Genetic counseling and prenatal molecular diagnosis for MLC families combined with clinical and genetic diagnosis are important in preventing MLC.Haplotype analysis with a combination of three microsatellite markers on chromosome X and sex determining region of Y chromosome is useful in detecting maternal cell contamination and avoiding its influence on prenatal diagnosis,and confirming the reliability of prenatal diagnosis.
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Epilepsies associated with KCNQ2 are a spectrum of disorders,and KCNQ2 mutations lead to a variety of phenotypes from the severest to the mildest,from early onset epileptic encephalopathy (EOEE) to benign familial neonatal convulsion (BFNC).The type and the position of KCNQ2 mutations may be associated with phenotypes,and provide a clue for assessing prognosis.KCNQ2 mutations lead to the reduced protein expression,abnormal distribution of potassium channels or decreased currents of potassium channels.It is the potential mechanism that KCNQ2 mutations cause different phenotypes.Recent studies have also found that KCNQ2 mutations may trigger seizures by enhancing potassium channel currents;however it needs further studies to verify.
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Subjective memory complaints (SMC) is increasingly recognized as the earliest prodromal stage of Alzheimer's disease.Individuals with SMC whose memory without measurable cognitive deficits,however,demonstrated some neurodegenerative brain changes.It would be more appropriate to prevent or postpone the AD process by interventing in this earlier stage of SMC,while relatively little is known about the brain plasticity in elderly with SMC.Therefore,further research is necessary in understanding the brain plasticity in SMC on the basis of further elucidating the pathophysiological mechanisms in this group of individuals.
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Objective To explore the curative efficacy of astragalus injection on blood lipids and bone mineral density in patients with hemiplegia after ischemic stroke. Methods From January, 2014 to June, 2015, 116 patients with hemiplegia after ischemic stroke were col-lected and radomly divided into control group (n=54) and observation group (n=62). The control group received acupuncture based on con-ventional treatments, while the observation group received astragalus injection in addition. National Institutes of Health Stroke Scale (NI-HSS) and Ability of Daily Living Scale (ADL) were used to assess the neurologic impairment and the ability of daily living. The curative ef-ficacy and the levels of blood lipids and bone mineral density were observed. Results Compared with the control group, the curative efficien-cy increased (χ2=3.960, P4.190, P0.05). The densities in forearm, femur and Ward's area in the hemiplegia side in-creased (t>2.060, P<0.05). Conclusion Astragalus injection is effective on hemiplegia after ischemic stroke, which can increase the curative efficacy, alleviate the neurologic impairment, promote the ability of daily living, improve the blood lipids and increase the bone mineral den-sity.
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Objective of the current study was to investigate the effectiveness and safety of levofloxacin in the treatment of lower respiratory tract infection. The study was carried out in hospital on 120 patients with lower respiratory tract infection from January 2014 to January 2015. Patients were randomly divided into control and observation groups, each group contained 60 patients. The control group was given the routine dose of levofloxacin, whereas the observation group received the high dose of levofloxacin. The clinical effectiveness and incidence rate of untoward reactions between the two groups were statistically analyzed and evaluated. Patients’ cure rate in the observation group was 53.33%, significantly higher than that of the control group which was only 36.67%. Their differences have statistical significance (P<0.05). Observation group demonstrated a very good total effective rate of 93.33%, compared to the control group (78.33%). Their differences have statistical significance (P<0.05). Incidence of adverse reactions in case of both the observation and control group patients, were relatively low, resulting insignificant statistical difference between the groups (P>0.05). This study shows better clinical curative effect of high doses of levofloxacin treating lower respiratory infection with minimum risk. This method, which can significantly improve the quality of patient treatment with low adverse reaction risk, is worth popularizing in clinical use.
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Aim of the present study was to evaluate the effect of flurbiprofen, which is a member of non-steroidal anti-inflammatory drug group (NSAIDs), on postoperative pain treatment. From September 2013 to May 2014, total of 250 patients were surveyed to perform a systematic evaluation of postoperative pain by comparing flurbiprofen with two other kinds of NSAIDs (diclofenac and ketorolac) and isotonic saline in a double-blind, randomized, placebo-controlled study. Patients were randomized for treatment: 65 cases received flurbiprofen, 60 cases received diclofenac sodium, 60 cases received ketorolac and 65 cases received the placebo (0.9% isotonic saline) (control group). After 24-hours of surgery patients treated with flurbiprofen, ketorolac, and diclofenac showed the lowermost PPI scores compared with those treated with 0.9% isotonic saline (P<0.05). Moreover, flurbiprofen-treated patients also had the lowest PRI(R)T scores (P<0.05). When the pain rating index was examined by subclass, a significantly lower PRI(R)S score was detected in the flurbiprofen group at 24 hours (P<0.05). However, at the 96-hour time point, no differences that were found in PPI and PRI[R] scores between the ketorolac, diclofenac, and flurbiprofen groups, whereas the control group was significantly less effective than the NSAID drugs. Flurbiprofen seemed to be the most effective NSAID for the treatment of pain after internal fixation of fracture, even though at 24 hours after surgery pain was at a maximum.
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Objective To investigate the effect of electroacupuncture on the rehabilitation of rheumatoid arthritis (RA) and level of nu-clear factor-κB (NF-κB), tumor necrosis factor-α(TNF-α) and interleukin 1β(IL-1β). Methods 140 cases of RA meeting the inclusion crite-ria were divided into control group and observation group equally according to therapeutic schemes. All the patients accepted medicine and rehabilitation training, while the observation group accepted electroacupuncture in addition. The effective rate and the symptoms were ob-served, the serum level of rheumatoid factor (RF), antistreptolysin O antibody (ASO), C-reactive protein (CRP), NF-κB, TNF-αand IL-1βwere tested before and after treatment. Results The effective rate was 92.8%in the observation group, which was significantly more than that of 80.0%in the control group (P<0.05). The joint pain index, joint tenderness index and joint swollenness index reduced in the observa-tion group compared with those in the control group (P<0.05), as well as the serum level of RF, ASO, CRP, NF-κB, TNF-αand IL-1β(P<0.05). Conclusion Electroacupuncture may improve the effects of rehabilitation training for RA and inhibit the inflammation, which may as-sociate with the inhibition of activation of NF-κB.
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Objective To observe the clinical effects and the safety of S-adenosy-L-methionine ( SAMe ) associated with ursodeoxycholic acid (UDCA) in treating intrahepatic cholestasis of pregnancy (ICP). Methods Eighty patients with ICP were randomly divided into treatment group ( treated with UDCA orally, 250 mg, TID and simultaneously with intravenous SAMe 1. 0 g, qd) and control group (treated with intravenous SAMe 1. 0 g, qd). Pruritus degree, serum total bilirubin (TB), total bile acid (TBA), glycocholic acid (CG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed before and after the treatment, and the pregnancy outcomes, such as the rate of premature, uterine-incision delivery and fetal distress were recorded. Results After treatment, the pruritus degree and the levels of TB, TBA, CG, ALT AST were decreased significantly compared with pretreatment in both groups. TB, TBA, AST and ALT of the treatment group decreased from (27.83±9. 34), (45. 62±18. 30) μmol·L-1, (195. 98±30. 22), (188. 69±29. 11) U·L-1 to (11. 81±4. 91), (11. 88±2. 23) μmol·L-1, (73. 59±21. 53), (67. 94±30. 53) U·L-1, respectively, and TB, TBA, AST, ALT of the control group decreased from (27. 49±7. 87), (49. 12±10. 39) μmol·L-1, (211. 93±34. 9), (210. 40±43. 39) U·L-1 to (16. 08± 6.23), (23.88±6.63) μmol·L-1, (87. 20±32. 52), (81. 77±35. 16) U·L-1, respectively (P0. 05), but the declines of TB, TBA and CG in treatment group were superior to those of the control group (P<0. 05). Conclusion In terms of improving pruritus, liver function and pregnancy outcome, single SAMe application could obtain similar effects compared with SAMe combined with UDCA, but SAMe combined with UDCA is more effective than the single SAMe application in decreasing the level of TBA and CG.
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Objective To investigate the inhibitory effect of testosterone on oxidized low-density lipoproteins ( ox-LDL)-stimulated phenotypic transition and proliferation of vascular smooth muscle cells ( VSMCs) in vitro, and to explore its possible mechanisms. Methods Rat VSMCs cultured in vitro were divided into control group, ox-LDL group(50μg/mlox-LDL),fetalbovineserum(FBS)group(10% FBS),andtestosteronegroups(5×10-8 or5×10-7 mol/L testosterone plus 50μg/ml ox-LDL) . The effect of testosterone on ox-LDL-induced proliferation of VSMCs was explored by WST-1 assay. The cell cycle distribution was determined using flow cytometry. Western blotting was used todetecttheexpressionsofmitofusin2(Mfn2),phosphorylatedextracellularsignal-regulatedkinases1/2(p-ERK1/2) , proliferating cell nuclear antigen ( PCNA) ,α-smooth muscle actin (α-SMA) ,and osteopontin ( OPN) . Results Compared with control group, the proliferation of VSMCs was promoted by ox-LDL, the number of VSMCs decreased in G0/G1 phase and increased in S phase significantly, the expression levels of Mfn2 and α-SMA were significantly reduced, and the expression levels of p-ERK1/2, PCNA, and OPN were significantly raised in ox-LDL group. Compared with ox-LDL group, the proliferation of VSMCs was inhibited, the number of VSMCs increased in G0/G1 phase and decreased in S phase in two testosterone groups, along with the increased expressions of Mfn2 andα-SMA, and the descended expressions of p-ERK1/2, PCNA, and OPN. Conclusions Testosterone inhibits phenotypic transition and proliferation of VSMCs induced by ox-LDL in vitro, which may be related to the up-regulated expression of Mfn 2 and the suppression of ERK1/2 pathway.