Clinical features, genetic variations and enzyme replacement therapy in five Chinese patients with Fabry disease / 中华肾脏病杂志

Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Efficacy of compound chamomile and lidocaine hydrochloride gel in prevention of complications related to laryngeal mask airway insertion / 中华麻醉学杂志

Objective:To evaluate the efficacy of compound chamomile and lidocaine hydrochloride gel in prevention of complications related to laryngeal mask airway (LMA) insertion.Methods:Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 18-60 yr, undergoing elective surgery with ventilation using LMA under general anesthesia, were divided into 3 groups ( n=30 each) using a random number table method: paraffin oil group (group A), compound lidocaine cream group (group B), and compound chamomile and lidocaine hydrochloride gel group (group C). The paraffin oil, compound lidocaine cream, and compound chamomile and lidocaine hydrochloride gel were evenly applied on the front, shoulder and back of the LMA before inserting the LMA in A, B and C groups, respectively.The severity of sore throat, oropharyngeal mucositis score, hoarseness score and occurrence in each time period (0-1 h, >1-6 h, >6-24 h, > 24-48 h) were recorded at 1, 6, 24 and 48 h after removal of the laryngeal mask.The stress responses during removal of the LMA and occurrence of drug-related adverse reactions within 48 h after removal of LMA were recorded. Results:Twenty-nine cases in group A, 28 cases in group B and 27 cases in group C completed the trial.Compared with group A, the severity of sore throat at each time point after removal of the LMA and incidence of sore throat in each time period were significantly decreased, the oropharyngeal mucositis score at 6, 24 and 48 h after removal of the LMA and the incidence of oropharyngeal mucositis in the time period >1-48 h were decreased, and the incidence of drug-related adverse reactions was increased in group C ( P<0.05). Compared with group B, the severity of sore throat at 6 h after removal of the LMA and incidence of sore throat > 1-48 h after removal of the LMA were significantly decreased, the oropharyngeal mucositis score at 6, 24 and 48 h after removal of the LMA and incidence of oropharyngeal mucositis in the time period >1-48 h after LMA removal were reduced, and the incidence of drug-related adverse reactions was decreased in group C ( P<0.05). There was no significant difference in the hoarseness score and incidence of hoarseness after removal of the LMA and incidence of stress responses during removal of the LMA among the three groups ( P>0.05). Conclusions:Compound chamomile and lidocaine hydrochloride gel has a certain efficacy in preventing complications related to LMA placement.

Influence of hypercholesterolemia on the risk of chronic kidney disease in the middle-aged and elderly population and gender differences / 中华肾脏病杂志

Objective:To explore the influence of hypercholesterolemia on the risk of chronic kidney disease (CKD) in the middle-aged and elderly population and the gender differences.Methods:The data came from the "Epidemiological Survey of Chronic Kidney Disease among Adults in Urban Communities in Henan Province". The subjects came from 20 communities in Henan Province, aged ≥45 years old. Groups were based on the quartile of total blood cholesterol level and gender. Multivariate logistic regression and Cochran-Armitage trend test were used to analyze the effect of hypercholesterolemia on the risk of CKD and its gender differences.Results:A total of 4 779 subjects were enrolled into the study, with 1 934 males (40.5%) and 2 845 females (59.5%). The age was (61.3±7.7) years old and the blood cholesterol was (5.0±1.0) mmol/L. The prevalence rates of hypercholesterolemia, albuminuria, and reduced estimated glomerular filtration rate (eGFR) were 10.7%(305/2 845), 6.4%(182/2 845) and 2.8%(79/2 845) in females and 12.7%(245/1 934), 6.9%(133/1 934) and 2.3%(45/1 934) in males respectively. Compared with Q1 group, the prevalence of reduced eGFR in females were higher in Q2 and Q4 groups (both P<0.05). Among males, the prevalence of albuminuria and reduced eGFR increased with increasing blood cholesterol quartile (Cochran-Armitage trend test Z=12.231, 8.862, both P<0.001). Multivariate logistic regression analysis showed that hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR ( OR=1.49, 95% CI 1.08-2.07, P=0.016 and OR=1.65, 95% CI 1.03-2.65, P=0.037, respectively). In subgroup analysis of different genders, female hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR, while male hypercholesterolemia was not an independent influencing factor ( OR=1.54, 95% CI 0.96~2.46, P=0.075; OR=1.89, 95% CI 0.93-3.89, P=0.082, respectively). Further subgroup analysis based on the interquartile range of serum cholesterol levels found that female hypercholesterolemia was an independent influencing factor for reduced eGFR in the Q2 and Q4 groups ( OR=2.35, 95% CI 1.29-7.61, P=0.003; OR=2.51, 95% CI 1.38-8.39, P=0.001). In males, hypercholesterolemia was an independent influencing factor for albuminuria in the Q2, Q3 and Q4 groups ( OR=1.80, 95% CI 1.01-3.41, P=0.047; OR=1.85, 95% CI 1.02-3.35, P=0.044; OR=2.33, 95% CI 1.33-4.33, P=0.002). Conclusions:Hypercholesterolemia is an independent risk factor for CKD in middle-aged and elderly population, and there are gender differences, which provides a new idea for clinical prevention and control of CKD.

A randomized controlled study of erlotinib versus pemetrexed combined with cisplatin in neoadjuvant therapy of stage ⅢA EGFR-mutant lung adenocarcinoma / 中华肿瘤杂志

Objective@#To evaluate the feasibility, efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) for neoadjuvant therapy.@*Methods@#Eighty-six patients with stage ⅢA EGFR-mutant lung adenocarcinoma were assigned to 2 groups (n=43 in each group) according to the random number table method: neoadjuvant targeted therapy group (single oral dose of erlotinib 150 mg per day, for 9 weeks) and neoadjuvant chemotherapy group (2 cycles of pemetrexed combined with cisplatin chemotherapy followed by 3- week discontinuation). Surgical treatment was underwent after imaging efficacy evaluation.@*Results@#In neoadjuvant targeted therapy group, 4 achieved complete response (CR), 25 achieved partial response (PR), giving an objective response rate (ORR) of 67.4%. In pathological response, 8 patients had grade Ⅰ, 20 patients had grade Ⅱ, giving a pathological response rate of 65.1%. The most frequent adverse events (AEs) were rash and diarrhea. In neoadjuvant chemotherapy group, 2 had CR and 17 had PR, giving an ORR of 44.2%. In pathological response, 3 patients had grade Ⅰ, 15 patients had grade Ⅱ, giving a pathological response rate of 41.9%. The main AEs were hematologic toxic effects. The ORR, histological efficacy and hematologic toxicity showed statistical significance between the two groups (P<0.05). The neoadjuvant targeted therapy group had 90.7% resection rate, (299.8±23.4) ml of hemorrhage volume during operation, (5.2±0.4) days of extubation time and 9.3% postoperative complication rate. Corresponding results were 83.7%, (308.9±22.7) ml, (5.4±0.6) days and 11.6% in neoadjuvant chemotherapy group, which showed no statistical significance (P>0.05).@*Conclusions@#Neoadjuvant targeted treatment for stage ⅢA lung adenocarcinoma harboring EGFR mutations. The regimen could be considered as a choice of neoadjuvant treatment for patients with stage ⅢA EGFR-mutant lung adenocarcinoma.

An unusual UMP C-5 methylase in nucleoside antibiotic polyoxin biosynthesis

Polyoxin is a group of structurally-related peptidyl nucleoside antibiotics bearing C-5 modifications on the nucleoside skeleton. Although the structural diversity and bioactivity preference of polyoxin are, to some extent, affected by such modifications, the biosynthetic logic for their occurence remains obscure. Here we report the identification of PolB in polyoxin pathway as an unusual UMP C-5 methylase with thymidylate synthase activity which is responsible for the C-5 methylation of the nucleoside skeleton. To probe its molecular mechanism, we determined the crystal structures of PolB alone and in complexes with 5-Br UMP and 5-Br dUMP at 2.15 Å, 1.76 Å and 2.28 Å resolutions, respectively. Loop 1 (residues 117-131), Loop 2 (residues 192-201) and the substrate recognition peptide (residues 94-102) of PolB exhibit considerable conformational flexibility and adopt distinct structures upon binding to different substrate analogs. Consistent with the structural findings, a PolB homolog that harbors an identical function from Streptomyces viridochromogenes DSM 40736 was identified. The discovery of UMP C5-methylase opens the way to rational pathway engineering for polyoxin component optimization, and will also enrich the toolbox for natural nucleotide chemistry.

The immunoregulative action of polysacchrides of Spirulina platensis in peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection / 中国药理学通报

Aim To investigate the immunoregulative action of polysacchrides of Spirulina platensis ( PSP ) on peripheral blood mononuclear cells ( PBMCs) in pa-tients with chronic hepatitis B virus infection. Meth-ods Proliferation and cycle of PBMCs from patients with chronic hepatitis B virus infection were measured by MTT colorimetry and flow cytometry respectively. The concentration of IFN-γ, IL-2 , IL-4 in supernatants of PBMCs were examined by ELISA. The mRNA ex-pression of IFN-γin PBMCs from patients with chronic hepatitis B virus infection was detected by RT-PCR. Results PSP could induce proliferation of PBMCs in patients with chronic hepatitis B virus infection. In ad-dition, PSP could increase the protein expression of IFN-γ and IL-2 in supernatants of PBMCs in patients with chronic hepatitis B virus infection, and PSP could also enhance the mRNA expression of IFN-γof PBMCs in patients with chronic hepatitis B virus infection. However, PSP inhibited the protein expression of IL-4 of PBMCs in patients with chronic hepatitis B virus in-fection. Conclusion PSP can promote the immune function and plays an important immunoregulation function on patients with chronic hepatitis B virus in-fection.

Methodological evaluation on enzymatic method for detecting HbA1c and influence of sample pre-processing on detection result / 重庆医学

Objective To evaluate the methodological performance of the new enzymatic method for detecting glycated hemo-globin(HbAIc)and its influencing factors.Methods HbAIc was detected by the enzymatic method.The precision,anti-interfer-ence,recovery rate,accuracy and the influence of pre-processing(anti-coagulation,preservation,centrifugation)on the detection re-sults were evaluated,its correlation with HPLC and the bias degree were analyzed.Results The within-run coefficients of variation (CVs)for high,middle and low value QC samples in the enzymatic assay were 1.04%,1.26% and 1.37% respectively and the be-tween-run CVs were 1.83%,2.24% and 2.64%,respectively;the enzymatic method showed the linear correlation with HPLC(r=0.996,P 0.05);the sample was centrifuged at 500,1 000 r/min(R=15 cm)for different time(1,2,5,10 min)and at 2 000 r/min for 1 min,their detection results had statistical differences compared with the sample centrifuged=3 000 r/min for 5 min (P <0.05).Conclusion The precision,anti-interference,accuracy and linearity range of the enzymatic method all conform to the clinical requirement.Compared with the conventional method,its correlation is good with small deviation,which can entirely satisfy the demand of the HbAIc detection in clinic.

Effects of wattle extract on Microcystic aeruginosa growth and the simulated mini fresh water ecosystem.

In recent years, there has been an apparent increase in the occurrence of harmful algal blooms in fresh waters. The value of applying the novel wattle extract (Acacia mimosa) to inhibit algal growth was assessed. Our results showed that the growth of Microcystis aeruginosa was successfully repressed by the plant extract and resulted in decreased extracellular microcystin-LR production. In the experiments, it showed a very effective inhibition in the stage of exponential growth (the largest decrease in level is 47.3% of the control) especially in nonsterile conditions, and the extract can reduce 14.5-24.7% cell density of the control in the stationary stage. In outdoor experiments, the extract reduced dissolved oxygen and pH, and selectively cut down cyanobacterial cell density to one-third of the control after 36 d of treatment. Accordingly, due to competitive inhibition in interspecies, other nanoalgae and small-sized aquatic animals declined, while macrozooplankton increased. Finally, more large algae were eliminated and thereby the water treated was clarified and the recovery of the freshwater ecosystem was promoted. Hence, the present study suggested a new and more effective and very low ecological risk approach to reduce nuisance blooms cyanobacteria in eutrophic water.

Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis

Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11'-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunA-tunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.

Therapeutic efficiency of seretide plus montelukast on patients with asthma and effect on the serum IL-6 and TNF-α / 中国基层医药

Objective To investigate the effect of seretide plus montelukast on clinical symptoms、pulmonary functions and the serum IL-6 and TNF-α of patients with asthma.Methods 73 cases patients with asthma were randomly divided into seretide group and seretide plus montelukast group and were treated respectively for two weeks.The clinical symptoms,lung functions and serum IL-6,TNF-α contents of patients were measured respectively before treatment and after two weeks treatment.Results After two weeks treatment,the clinical symptom scores、FEV1.0、FVC and PEFR of two groups had significantly changed than that before treatment(P<0.05);Each index was further compared after treatment,and it was found that two groups had significant differernces statistically (P<0.05),these showed that combination of seretide and montelukast could significantly enhance the therapeutic effect.After treatment,the TNF-α and IL-6 contents in the peripheral blood of seretide group and seretide plus montelukast group had both significantly reducted (P<0.05 or P<0.01);The TNF-α and IL-6 contents of seretide plus montelukast group had reduced more significantly than that of the seretide group(P<0.05).Conclusion The seretide plus montelukast group could improve the clinical symptoms and pulmonary function of patients with asthma,and the action mechanism might be related to lower the serum IL-6 and TNF-α contents.

Diagnosis of osteoporosis by vertebral bone mineral density measurement with quantitative computed tomography / 中国矫形外科杂志

[Objective] To evaluate the clinical value of diagnosing osteoporosis with vertebra bone mineral density(BMD) by measurement with quantitative computed tomography (QCT) . [ Method] BMD in of lumbar vertebrae (L<,1～4>)were measured by QCT in 53 healthy middleaged persons or elderly persons (group A) and 68 osteoporosis patients ( groupB) . [Result] BMD in group A declined obviously as age increasing with significant differences (P<0. 01) . In group B,all 68 patients showed osteoporosis according to the diagnostic standard of BMD≤x -2. OSD. Sixty patients showed osteoporosis ifthe diagnostic standard was set to BMD ≤ x -2. 5SD. The BMD values of different age group was lower than the bone quantityblock values. [Conclusion] As a method for diagnosing osteoporosis, QCT has advantages of high sensitation, being precise,being reproducible and is easy for applying. It would be more practical and could decrease mis - diagnosing if the diagnosticstandard was BMD≤x-2.OSD.

Analysis of lumbar bone mineral density of 575 individuals by QCT examination / 中国矫形外科杂志

[Objective]To analyze the relation of age and sex with the incidence of physical examinees with osteoporosis and low bone mass of vertebras.[Method]Quantitative CT(QCT) was used to examine and analyze the lumbar bone mineral density in 575 physical examinees.The data was analyzed by statistical software SAS 9.0.[Result]Bone mineral density(BMD)decreased with age after 50 years old.The occurrence rates of osteoporosis were 56.34% for females at 50-59 years,87.80% at 60-69 years,97.22% at 70-79 years and 100% at 80-89 years,25.44% for males at 50-59 years,50.64% at 60-69 years,66.66% at 70-79 years,and 90.91% at 80-89 years.[Conclusion]The incidence of osteoporosis is positively related with the age.The occurrence rate of osteoporosis increases with increasing age.It is obviously higher in females than in males.