Study on the extensibility of platelet donor gene database in Shaanxi / 中国输血杂志

【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.

Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache / 中国中药杂志

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Clinical and genetic characteristics of children with primary dilated cardiomyopathy / 中国当代儿科杂志

OBJECTIVES@#To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM).@*METHODS@#A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data.@*RESULTS@#Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05).@*CONCLUSIONS@#There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Application of capsulorhexis-chop forceps assisted prechop technique in hard cataract phacoemulsification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the advantages of capsulorhexis-chop forceps assisted prechop(CCFP)technique in hard cataract phacoemulsification.METHODS: Prospective study. A total of 100 cases(100 eyes)with age-related grade IV hard cataract were included and randomly divided into 2 groups according to random number table, with 50 patients(50 eyes)in CCFP technique group(group A)and 50 cases(50 eyes)in stop-and-chop technique group(group B). The corneal endothelial cell count before and after operation, intraoperative US time, postoperative corneal endothelial cell loss rate, corneal edema grade at 1 and 7d and best corrected visual acuity(BCVA)were compared and statistically analyzed.RESULTS: The mean US time of group A was lower than that of group B [26.66(16, 40)s vs. 36.12(23, 46)s; Z=-5.56, P&#x003C;0.01]. The mean corneal endothelial cell count in group A was higher than that in group B at 3mo after operation(2308.12±368.18cell/mm2 vs. 2104.06±379.87cell/mm2; t=2.728, P=0.008), and the loss rate of corneal endothelial cells in group A was lower than that in group B at 3mo after operation [10%(8%, 12%)vs. 17%(14%, 20%); Z=13.231, P&#x003C;0.01]. The number of eyes with corneal edema of grade 0, 1, 2, 3 and 4 on 1d after surgery was 0, 23, 21, 6 and 0 in group A, respectively, while it was 0, 9, 26, 15 and 0 respectively in group B. Corneal edema in group A was less than that in group B(Z=10.514, P=0.005). The BCVA of group A was better than that of group B at 1d after operation, and there was significant difference in the number of eyes with different BCVA grades between the two groups(Z=7.176, P=0.029). There was no significant difference in the number of eyes with different grades of BCVA between the two groups at 3mo after surgery(Z=2.377, P=0.372).CONCLUSION: Compared with the stop-and-chop technique, CCFP technique uses less ultrasonic energy, has less damage to corneal endothelial cells and is suitable for hard cataract surgery.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Research progress in the pathogenesis mechanism of dental fluorosis / 中华口腔医学杂志

Dental fluorosis is a developmental disturbance of dental enamel caused by excessive fluoride intake during tooth development, leading to the changes in morphology, structure and function of tooth enamel, which can affect the aesthetics and function of teeth. There are many factors which may account for the occurrence of dental fluorosis. However, the pathogenesis mechanism underlying dental fluorosis has not been fully clarified.In recent years, researches in the fields of fluoride-induced stress response pathways, signaling pathways and apoptosis at the molecular and genetic level had provided extensive knowledge of dental fluorosis. This article focuses on the latest research progress in the mechanism of dental fluorosis, which include the effects of fluoride on ameloblasts and enamel matrix proteins, genetic polymorphism and dietary nutrients, in order to provide new references for the targeted prevention and treatment of dental fluorosis.

Applications of digital medical techniques for dental dysplasia / 中华口腔医学杂志

Dental dysplasia are abnormalities in teeth structure, morphology, number and eruption caused by genetic and environmental factors during dental development. Digital medical techniques, as the current hot spot of medical research, bring great challenges and opportunities to modern stomatology. The applications of digital techniques, such as digital diagnosis method, digital virtual simulated design, three-dimensional printing, static and dynamic guidance and artificial intelligence, can provide a more accurate, efficient, automatic and intelligent modern concepts and patterns for epidemiology, diagnosis, multidisciplinary treatment and outcome assessment of dental developmental anomalies.

Analysis of the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.

Establishment of Flp-In CHO recombinant cell lines stably expressing CYP2A13 and CYP2A13/POR / 中国药理学通报

Aim To construct Flp-In CHO cell line(CYP2A13-CHO)stably expressing cytochrome P450 family 2 subfamily A member 13(CYP2A13)and Flp-In CHO cell line(CYP2A13-POR-CHO)stably co-expressing CYP2A13 and cytochrome P450 oxidoreductase(POR), from which a cell line with better metabolic activity is selected.Method In our previous study, we had constructed a Flp-In CHO cell line(POR-Flp-In CHO)stably expressing POR using lentiviral vector.The recombinant plasmids of pcDNA5/FRT-CYP2A13 were constructed and transfected into Flp-In CHO cells and POR-Flp-In CHO cells through LipofectamineTM 2000.The expression and activity of CYP2A13 were detected by real-time quantitative PCR(qRT-PCR), Western blot and Aflatoxin B1(AFB1)/4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)cytotoxicity assay and the metabolic activity was compared between CYP2A13-CHO and CYP2A13-POR-CHO.Results Compared with non-transfected cells, the mRNA and protein expression of CYP2A13 in CYP2A13-CHO and CYP2A13-POR-CHO cells both increased significantly.Besides, compared with CYP2A13-POR-CHO, CYP2A13-CHO cells were more sensitive to AFB1 and NNK.Conclusions The Flp-In CHO cell line stably expressing CYP2A13 and with better metabolic activity has been established successfully, which provides a tool for screening of pre-carcinogens that can be metabolically activated by CYP2A13.

The capacity evaluation and utilization strategy of the platelet donor database with known HLA/HPA genotype in Shaanxi / 中国输血杂志

【Objective】 To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. 【Methods】 A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. 【Results】 The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. 【Conclusion】 The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.

Virtual Autopsy Morphological Features of Drowning / 法医学杂志

OBJECTIVES@#To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning.@*METHODS@#In this study, 7 corpses were selected as the research objects. The image data of corpses were collected by computed tomography (CT) before conventional autopsy. The characteristics of corpses were observed through image reading, combined with virtual measurement indexes, and compared with 15 non-drowned corpses.@*RESULTS@#The postmortem CT of drowning showed the more fluid in respiratory tract than the non-drowning, and ground-glass opacities in the lung. The statistical volume of fluid in the sinus (maxillary sinus and sphenoid sinus) was (10.24±4.70) mL in drowning cases and (2.02±2.45) mL in non-drowning cases. The average CT value of fluid in the sinus, left atrial blood and gastric contents in drowning cases were (15.91±17.20), (52.57±9.24) and (10.33±12.81) HU, respectively, which were lower than those in non-drowning cases (P<0.05).@*CONCLUSIONS@#The comprehensive consideration of multiple characteristic image manifestations and the virtual measurement indexes are helpful to the forensic pathological diagnosis of drowning. Virtual autopsy can be used as an auxiliary method in the forensic diagnosis of drowning.

Analysis of etiological characteristics and establishment of prediction model of postoperative infections in patients undergoing oral squamous cell carcinoma surgery with free flap reconstruction / 北京大学学报(医学版)

OBJECTIVE@#To investigate the characteristics of pathogen infection and to establish a prediction model of infections in oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction.@*METHODS@#The retrospective cohort study consisted of 1 596 patients undergoing tumor resection and free flap reconstruction for oral squamous cell carcinoma from January 2018 to December 2020. According to the postoperative infection, the patients were divided into the infected group (n=154) and non-infected group (n=1 442). The characteristics of pathogens were analyzed in the infected patients. The primary outcome variable was postoperative infection, and Logistic regression was used to determine risk factors of the infection. The prediction model was established and the discriminatory accuracy of the model was evaluated using receiver operating characteristic (ROC) curve.@*RESULTS@#Totally 154 cases were infected in the 1 596 cases undergoing surgery with free flap reconstruction, and the infection rate was 9.65%. The most frequent sites of infection were the surgical wound and respiratory tract. A total of 268 pathogens were isolated and cultured, including 240 strains of Gram-negative bacteria, accounting for 89.55%, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae; 23 strains of Gram-positive bacteria, accounting for 8.58%, mainly Enterococcus faecalis and Staphylococcus aureus; and 5 strains of fungi, accounting for 1.87%. The isolated Pseudomonas aeruginosa had high resistant rate to imipenem and meropenem, and was sensitive to antibiotics, such as ciprofloxacin. The isolated Staphylococcus aureus had high resistant rate to erythromycin and clindamycin, and was sensitive to vancomycin. According to the multivariate Logistic analysis, four independent variables were significantly associated with an increased risk of postoperative infection (P < 0.05): clinical N category≥1, the American Society of Anesthesiologists (ASA) grade ≥2, tracheotomy and length of hospital stay >13 d. The prediction model was established based on these factors and the expression of the risk prediction model was as follows: predicted probability value P=1/(1+e-a), a=-0.803+0.674×(clinical N category ≥1)+0.518×(the ASA grade ≥2)+0.918×(tracheotomy)+1.581×(length of hospital stay >13 d), Hosmer-Lemeshow χ2=10.647, P=0.223, the degree of fitting of the model was good. The area under the ROC curve was 0.818 and 95%CI of the model for predicting infection was 0.789-0.846.@*CONCLUSION@#Oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction are prone to have a high incidence of postoperative infection and Gram-negative bacteria are the main pathogens causing an infection. The established prediction model is of good predictive effect. Rational antimicrobial use coupled with awareness of infection control measures is paramount to reduce the incidence of postoperative infection in the oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction.

Application and prospect of static/dynamic guided endodontics for managing pulpal and periapical diseases / 中华口腔医学杂志

Root canal therapy and endodontic surgery are conventional treatments for pulpal and periapical diseases. Compared with naked-eye operations, the application of dental operating microscope has enhanced the procedural accuracy and prognosis efficiently. However, root canals with pulp calcification/obliteration, apical lesions with thick cortical bone or adjacent to important anatomic structures are even challenging for experienced operators to achieve predictable clinical outcomes. Recently, with the advances in the field of digitalized information sciences, the above mentioned complicated endodontic cases can be solved under static and dynamic guidance. Before the treatment begins, virtual path is designed from data collected by cone-beam CT and oral image scanning using guidance software. Afterwards, root canal therapy and endodontic surgery can be performed precisely under the assistance of three-dimensional printed guide or dynamic guidance system. The present review describes the classification, features and clinical applications of the guided endodontics.

Establishment of fingerprint ，content determination and chemical pattern recognition of decoction pieces and dispensing granules of Gardenia jasminoides / 中国药房

OBJECTIVE To establish the fingerp rint of decoction pi eces and dispensing granules of Gardenia jasminoides ，to determine the contents of 6 components，so as to evaluate its quality combined with chemical pattern recognition. METHODS High performance liquid chromatography （HPLC）was used. Using geniposide as the reference ，Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition）was used to draw the fingerprints of 20 batches of G. jasminoides decoction pieces and 10 batches of G. jasminoides dispensing granules. Similarity evaluation and common peaks identification were conducted. The same HPLC method was adopted to determine the contents of deacetyl asperulosidic acid methyl ester ，geniposide， picrocrocin，rutin，crocin-Ⅰ and crocin- Ⅱ. ORIGIN 9.1 software was used for hierarchical clustering analysis ，and SIMCA 16.0 software was used for principal component analysis （PCA） and partial least squares-discriminant analysis. The differential components affecting the quality of decoction pieces and dispensing granules were screened by taking the variable importance in projection（VIP）value＞1 as the standard. RESULTS There were 24 common peaks for both 20 batches of G. jasminoides decoction piece and 10 batches of G. jasminoides dispensing granules ；a total of 22 common peaks were found in the fingerprints of 30 batches of samples ，and the similarity was not lower than 0.96；six common peaks were identified ，i.e. deacetyl asperulosidic acid methyl ester （peak 2），geniposide（peak 6），picrocrocin（peak 9），rutin（peak 11），crocin-Ⅰ（peak 15），crocin-Ⅱ（peak 17）. Average contents of above 6 components in G. jasminoides decoction pieces were 1.04，57.00，1.30，1.03，9.63 and 0.99 mg/g， respectively；those of G. jasmin oides dispensing granules were 0.96，17.04，0.37，0.27，0.73 and 0.04 mg/g，respectively. PCA results showed that G. jasminoides decoction pieces and G. jasminoides dispensing granules were clustered into respective one category ，which was consistent with results of cluster analysis. There were 9 common peaks with VIP value ＞1， which were 16，14，3，17（crocin-Ⅱ），15（crocin-Ⅰ），18， 22， 2 （deacetyl asperulosidic acid methyl ester） and 21. CONCLUSIONS The estab lished fingerprint and content determination method are simple and reproducible. Combined with chemical pattern recognition ，it can be used to evaluate the quality of decoction pieces and dispensing granules of G. jasminoides . Nine corresponding components represented by peak 16 and so on are the differential components that affect the quality of them.

Effect of Acute Myeloid Leukemia Cells on the Proliferation and Apoptosis of Bone Marrow-Derived Mesenchymal Stromal Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of acute myeloid leukemia cells in leukemia-microenvironment on proliferation and apoptosis of bone marrow-derived mesenchymal stromal cells (BM-MSC).@*METHODS@#Acute myeloid leukemia (AML) murine models overexpressing MLL-AF9 were established. The number of BM-MSC of wild type (WT) and AML-derived mice were analyzed by flow cytometry. Morphology and growth differences between WT and AML-derived BM-MSC were analyzed by inverted fluorescence microscope. Proliferation and apoptosis of BM-MSC between these two groups were detected by Brdu and Annexin V/PI.@*RESULTS@#Compared with WT-derived BM-MSC, the number and proliferation rate of AML-derived BM-MSC significantly increased (P<0.01, P<0.001), while apoptosis rate decreased (P<0.05). When cultured in vitro, BM-MSC grew faster under conditional medium.@*CONCLUSION@#AML cells can promote proliferation and inhibit apoptosis of BM-MSC.

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

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

Comparison of different protocols for protein extraction from formalin-fixed paraffin embedded esophageal squamous cell carcinoma tissues / 解剖学报

Objective To explore protein extraction efficiency from formaldehyde-fixed paraffin embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue samples with different protocols. Methods Six different lysis buffers with 100 °C or 105 °C. treatments were used for protein extraction, followed by evaluation of protein quantity and quality with Bradford, sodium dodecyl sulfate Polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis, Western blotting and immunohistochemistry (IHC), using 8 FFPE samples of ESCC. Results The optimal method for protein extraction from FFPE ESCC tissue was Laemmli lysis buffer (Buffer 4) treated with 100 °C incubation, evidenced by highest amount of protein recovery. Western blotting and IHC method measured consistent 14-3-3σ expression in FFPE ESCC tissue samples. Protein precipitated by two volumes of acetonitrite acetonitrile(ACN) (0.1% trifluoroacetic acid) relative to protein amount reduced background staining on SDS-PAGE gels by commassie staining. Conclusion Laemmli lysis buffer combined with 100 °C incubation has the highest protein extraction efficiency from FFPE ESCC tissue samples for Western blotting measurement of protein biomarkers, and ACN protein precipitation can further eliminate residual cross- linked protein by FFPE.

Association of HLA-DRB1, -DQB1, -DPB1 alleles and haplotype polymorphisms with acute myeloid leukemia (non-M3) in northern Han population / 中国输血杂志

【Objective】 To explore the association of HLAII(-DRB1, -DQB1, -DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia (AML) in northern Han population. 【Methods】 A total of 308 AML (non-M3) patients (patient group) and 824 unrelated healthy bone marrow donors (control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes (SSO) with LABScan® 3D platform. Frequencies of HLA II alleles and haplotypes were calculated with Arlequin 3.5.2.2 software. The odds ratio (OR) of AML was also calculated for case-control study. 【Results】 By χ2 test and correction, an increased frequency of HLA-DRB1*07∶01(14.61% vs 9.53%, P<0.01), HLA-DQB1*02∶02(12.82% vs 8.31%, P<0.01), HLA-DQB1*06∶02(11.53% vs 8.74%, P<0.05) and HLA-DPB1*17∶01(5.84% vs 3.16%, P<0.01) among AML patients was discovered in significant comparison with the control group. After Bonferroni correction, the frequency of HLA-DRB1*07∶01(Pc<0.05), HLA-DQB1*02: 02(Pc<0.05) and HLA-DPB1*17∶01(Pc<0.05) in AML patients were still higher than those in the control group, which had a strong positive correlation with AML (OR=1.62 (95% CI=1.23~2.14), 1.62(95% CI=1.21~2.18) and 1.91(95% CI=1.23~2.94), respectively. The frequency of two loci haplotype HLA-DRB1*07∶01-DQB1*02∶02 in AML patients was still higher than that of the control group after Bonferroni correction (12.66% vs 8.19%, Pc<0.05). The frequency of the 3 loci haplotype HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01, as a susceptible haplotype of AML, was higher than that of the control group and was strongly correlated with AML. 【Conclusion】 The data on the association of HLA II (-DRB1, -DQB1, -DPB1) alleles and haplotype polymorphisms with AML in northern Han populations was obtained in this study. HLA-DRB1*07∶01, HLA-DQB1*02∶02, HLA-DPB1*17∶01 and the HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01 haplotype are the risk genes and susceptible extended haplotype for AML. The risk prediction based on HLA haplotype might be more accurate than that based on single allele.

A retrospective study to compare the treatment outcomes with and without surgical navigation for fracture of the orbital wall / 中华创伤杂志(英文版)

PURPOSE@#To evaluate the outcomes with and without aid of a computer-assisted surgical navigation system (CASNS) for treatment of unilateral orbital wall fracture (OWF).@*METHODS@#Patients who came to our hospital for repairing unilateral traumatic OWF from 2014 to 2017 were included in this study. The patients were divided into the navigation group who accepted orbital wall reconstruction aided by CASNS and the conventional group. We evaluated the surgical precision in the navigation group by analyzing the difference between actual postoperative computed tomography data and preoperative virtual surgical plan through color order ratios. We also compared the duration of surgery, enophthalmos correction, restoration of orbital volumes, and improvement of clinical symptoms in both groups systemically. Quantitative data were presented as mean ± SD. Significance was determined by the two-sample t-test using SPSS Version 19.0 A p < 0.05 was considered statistically significant.@*RESULTS@#Seventy patients with unilateral OWF were included in the study cohort. The mean difference between preoperative virtual planning and actual reconstruction outcome was (0.869 ± 0.472) mm, which means the reconstruction result could match the navigation planning accurately. The mean duration of surgery in the navigation group was shorter than it is in the control group, but not significantly. Discrepancies between the reconstructed and unaffected orbital-cavity volume and eyeball projection in the navigation group were significantly less than that in the conventional group. One patient had remnant diplopia and two patients had enophthalmos after surgery in the navigation group; two patients had postoperative diplopia and four patients had postoperative enophthalmos in the conventional group.@*CONCLUSION@#Compare with the conventional treatment for OWF, the use of CASNS can provide a significantly better surgical precision, greater improvements in orbital-cavity volume and eyeball projection, and better clinical results, without increasing the duration of surgery.