Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors

Background@#and Purpose Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects. The risk factors for telbivudine-induced myopathy (TIM) are not yet clear. @*Methods@#This study characterized the clinical, magnetic resonance images (MRI), and pathological features of 12 TIM cases. A group of telbivudine-tolerant (TT) patients with CHB who received regular telbivudine treatment during the same period without the occurrence of myopathy was collected. Demographic and clinical factors were compared between the patients with TIM and the TT controls. Factors independently associated with TIM were identified using logistic regression analysis. @*Results@#The patients with TIM (males/females: 7/5, mean age: 57 years) developed myopathy after using telbivudine for a median period of 19.5 months. Muscle histopathology revealed abnormal proliferation, subsarcolemmal or sarcoplasmic accumulations, and ultrastructural defects of mitochondria. When compared with TT cases, patients with TIM had a lower estimated glomerular filtration rate and were more frequently positive for hepatitis B e antigen (HBeAg). @*Conclusions@#Mitochondrial abnormalities are characteristic histopathological features, and impaired renal function and HBeAg positivity are risk factors for TIM. Telbivudine-induced mitochondrial dysfunction and immune activation related to mitochondrial damage and HBeAg serostatus changes may underlie TIM. Constant clinical surveillance of myopathy during telbivudine treatment is needed due to the significant latency of its development. Dose adjustment for impaired renal function does not eliminate the risk of TIM occurrence.

Prognostic analysis of children with Philadelphia chromosome-like acute lymphoblastic leukemia common genes / 中华儿科杂志

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ2=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ2=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Effect of exogenous trivalent iron ions on tau phosphorylation and aggregation in SH-SY5Y cells / 环境与职业医学

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl3) at four concentrations (10, 100, 200, and 400 mg·L−1). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl3 at 10 or 200 mg·L−1. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl3 at 10 and 200 mg·L−1. After dilution with phosphate buffered saline (PBS), FeCl3, human tauR3, and FeCl3 + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl3 and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl3 exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L−1 groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L−1 FeCl3 group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl3 exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L−1 group was up-regulated by 72.7% (P<0.01). After FeCl3-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L−1 group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl3 groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl3 + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.

Non-muscle myosin heavy chain 9 gene-related disorders with thrombocytopenia: report of two pedigrees and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. Methods: The basic information, clinical features, gene variants and laboratory tests of MYH9-RD patients from 2 pedigrees confirmed in the First Affiliated Hospital of Zhengzhou University in November 2021 and July 2022 were analyzed retrospectively. "Non-muscle myosin heavy chain 9 related disease" "MYH9" and "children" were used as key words to search at Pubmed database, CNKI and Wanfang database up to February 2023. The MYH9-RD gene variant spectrum and clinical data were analyzed and summarized. Results: Proband 1 (male, 11 years old) sought medical attention due to epistaxis, the eldest sister and second sister of proband 1 only showed excessive menstrual bleeding, the skin and mucous membrane of the their mother were prone to ecchymosis after bumping, the uncle of proband 1 had kidney damage, and the maternal grandmother and maternal great-grandmother of proband 1 had a history of cataracts. There were 7 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that the proband 1 MYH9 gene had c.279C>G (p.N93K) missense variant, and family verification analysis showed that the variant was inherited from the mother. A total of 4 patients including proband 1 and family members were diagnosed with MYH9-RD. The proband 2 (female, 1 year old) sought medical attention duo to fever and cough, and the father's physical examination revealed thrombocytopenia. There were 2 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that there was a c.4270G>A (p.D1424N) missense variant in the proband 2 MYH9 gene, and family verification analysis showed that the variant was inherited from the father. A total of 2 patients including proband 2 and his father were diagnosed with MYH9-RD. A total of 99 articles were retrieved, including 32 domestic literatures and 67 foreign literatures. The MYH9-RD cases totaled 149 pedigrees and 197 sporadic patients, including 2 pedigrees in our study. There were 101 cases with complete clinical data, including 62 sporadic cases and 39 pedigrees. There were 56 males and 45 females, with an average age of 6.9 years old. The main clinical manifestations were thrombocytopenia, skin ecchymosis, and epistaxis. Most patients didn't receive special treatment after diagnosis. Six English literatures related to MYH9-RD caused by c.279C>G mutation in MYH9 gene were retrieved. Italy reported the highest number of cases (3 cases). Twelve literatures related to MYH9-RD caused by c.4270G>A mutation in MYH9 gene were retrieved. China reported the highest number of cases (9 cases). Conclusions: The clinical manifestations of patients in the MYH9-RD pedigrees varied greatly. MYH9 gene c.279C>G and c.4270G>A mutations are the cause of MYH9-RD.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

Clinical characteristics and prognosis of 83 children with newly treated hepatoblastoma / 中华儿科杂志

Objective: To investigate the clinical features, survival and prognostic risk factors of children with hepatoblastoma (HB). Methods: Clinical data of 83 children with newly treated HB at the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2019 were analyzed retrospectively. The sex, age, first clinical manifestations, pretreatment extent of disease (PRETEXT) stages, pathological types, initial alpha-fetoprotein (AFP), treatment methods and treatment outcome of all patients were summarized. The children diagnosed before 2018 were treated with "Wuhan Protocol", and those who diagnosed after 2018 were treated with the "Expert Consensus for Multidisciplinary Management of Hepatoblastoma"(CCCG-HB-2016) protocol. Kaplan-Meier survival analysis was used to calculate the survival rate, Log-Rank test was used in univariate analysis, and the Cox regression model was used in multivariate prognosis analysis. Results: Among 83 cases, there were 51 males and 32 females. The age of onset was 25.2 (9.0, 34.0) months old, and 64 cases (77%) were under 3 years old. The most common first clinical manifestation was abdominal mass in 45 cases (54%). There were 8 cases of PRETEXT stage Ⅰ, 43 cases of stage Ⅱ, 20 cases of stage Ⅲ and 12 cases of stage Ⅳ. During the follow-up period of 40 (17, 63) months, the 1-year overall survival (OS) rate and event-free survival (EFS) rate were (84±4) % and (79±5) %, respectively, and 5-year OS rate and EFS rate were (78±5) % and (76±5) %, respectively. Fifty-five cases were treated with "Wuhan Protocol", and the 5-year OS and EFS rate were (73±6) % and (71±6) %, respectively. Twenty-eight cases were treated with CCCG-HB-2016 protocol, and the 5-year OS and EFS rate were (88±7) % and (82±9) %, respectively. Multivariate COX regression analysis showed that AFP did not turn negative after 3 courses of postoperative chemotherapy (HR=9.228, 95%CI 1.017-83.692) and PRETEXT stage Ⅳ (HR=6.587, 95%CI 1.687-25.723) were independent risk factors affecting the prognosis of children with HB. Conclusions: The "Wuhan Protocol" and CCCG-HB-2016 protocol were effective in the treatment of children with HB. AFP did not turn negative after 3 courses of postoperative chemotherapy and PRETEXT stage Ⅳ were independent risk factors affecting the prognosis of children with HB.

Characteristics of the Distance and Space Required for Knife Slashing Using a Motion Capture System / 法医学杂志

OBJECTIVES@#To investigate the relationship between the perpetrator's sex, victim's position and slashing location as well as anthropometric parameters on distance and space required for slashing, to provide the theoretical basis for the judgment of whether the crime scene was consistent with the criminal activity space.@*METHODS@#The kinematics data of 12 male and 12 female subjects slashing the neck of standing and supine mannequins as well as the chest of the standing mannequins with a kitchen knife were obtained by using a 3D motion capture system. The relationship between the perpetrator's sex-victim's position, the perpetrator's sex-slashing location, and anthropometric parameters and the distance and space required for the slashing were analyzed by two-factor repeated measures ANOVA and Pearson correlation analysis respectively.@*RESULTS@#Compared with slashing the neck of supine mannequins, the distance (L) and normalized L (l) of slashing the neck of standing mannequins were greater, while vertical distance (LVR) and normalized LVR (lVR) of the knife side were smaller. Compared with slashing the neck of standing mannequins, the L and l slashing the chest of standing mannequins were greater, while LVR and lVR were smaller. Horizontal distance (LHR) and normalized LHR (lHR) of the knife side in males were greater than that in females. Height and arm length were positively correlated with L, LHR, and LVR when striking the standing mannequins.@*CONCLUSIONS@#When slashing the neck of supine or standing victims, the slashing distance is shorter and the slashing height is greater. Furthermore, the distance and space required for slashing are correlate with anthropometric parameters.

Analysis on Medication Regularity of Traditional Chinese Medicine in Treatment of Intermediate and Advanced Non-small Cell Lung Cancer Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore medication regularity of traditional Chinese medicine （TCM） in the treatment of non-small cell lung cancer （NSCLC） and thereby to lay a theoretical basis for clinical medication and drug development. MethodArticles on clinical treatment of intermediate and advanced NSCLC with TCM in the past 40 years were retrieved from CNKI， which were taken the data source. Then the articles were screened to establish a formula database， followed by frequency statistics， association rule analysis， cluster analysis， factor analysis， and complex network construction. ResultA total of 307 eligible articles were screened out， involving 483 formulas. The common syndrome of intermediate and advanced NSCLC was the deficiency of both Qi and Yin， with the common syndrome elements of Qi deficiency， Yin deficiency， phlegm， blood stasis， pathogenic heat （fire）， toxin， and pathogenic dampness. The frequently used medicinals mainly had the functions of tonifying deficiency， clearing heat， resolving phlegm and relieving cough and dyspnea， promoting urination and draining dampness， and activating blood and resolving stasis. The high-frequency medicinals were Astragali Radix， Glycyrrhizae Radix et Rhizome， Ophiopogonis Radix， Fritillariae Thunbergii Bulbus， and Poria， which were mainly cold， bitter， sweet， and pungent， with tropism at lung， spleen， and stomach. The association rule analysis yielded 17 rules with strong association. Ten common factors were extracted from the factor analysis， and cluster analysis classified the medicinals into 5 groups. Complex network analysis suggested that the core formula was modified Liujunzi Tang and Yiqi Yangyin Jiedu prescription. ConclusionThe treatment principle for intermediate and advanced NSCLC is replenishing Qi and nourishing Yin， invigorating spleen and resolving phlegm， clearing heat and detoxifying， promoting blood circulation and removing blood stasis. The core combinations new prescription discovered by data mining are of important guiding significance， but they should be further verified in clinical practice and by experiments based on the theory of TCM.

Characteristics of N6-methyladenosine modification patterns in t(8;21) acute myeloid leukemia / 南方医科大学学报

OBJECTIVE@#To investigate the relationship between AML1-ETO (AE) fusion gene and intracellular N6-methyladenosine (m6A) modification pattern in t(8;21) acute myeloid leukemia (AML).@*METHODS@#RNA m6A sequencing was performed in SKNO-1 and AE knockdown SKNO-1 (SKNO-1 siAE) cells using RNA-protein co-immunoprecipitation and high-throughput sequencing (methylated RNA immunoprecipitation sequencing, MeRIP-Seq) to analyze the changes in m6A modification of the entire transcriptome. Transcriptome sequencing (RNA-seq) was performed using high-throughput sequencing. The differentially modified mRNAs were further functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The changes in m6A-related enzyme expressions were detected using real-time PCR.@*RESULTS@#A total of 26 441 genes were identified in AE knockdown AML cells and AE-expressing cells, containing 72 036 m6A peaks. AE knockdown caused a reduction of the number of intracellular m6A peaks from 37 042 to 34 994, among which 1278 m6A peaks were significantly elevated and 1225 were significantly decreased; 1316 genes with newly emerged m6A modification were detected and 1830 genes lost m6A modification after AE knockdown. The differential peaks were mainly enriched in pathways involving cancer and human T-lymphocytic leukemia virus I. RNA-seq results showed that 2483 genes were up-regulated and 3913 genes were down-regulated after AE knockdown. The combined analysis of MeRIP-Seq and RNA-Seq results revealed relatively high expression levels of m6A-modified genes as compared with the genes without m6A modification (SKNO-1: 0.6116±1.263 vs 2.010±1.655, P < 0.0001; SKNO-1 siAE: 0.5528±1.257 vs 2.067±1.686, P < 0.0001). The m6A modified genes located in the 3'UTR or 5 'UTR had significantly higher expression levels than those located in exonic regions (SKNO-1: 2.177± 1.633 vs 1.333 ± 1.470 vs 2.449 ± 1.651, P < 0.0001; SKNO-1 siAE: 2.304 ± 1.671 vs 1.336 ± 1.522 vs 2.394 ± 1.649, P < 0.05). Analysis of RNA-seq data identified 3 m6A-related enzymes that showed significantly elevated mRNA expression after AE knockdown, namely WTAP, METTL14, and ALKBH5 (P < 0.05), but the results of real-time PCR showed that the expressions of WTAP and ALKBH5 were significantly increased while the expression of METTL14 was lowered after AE knockdown (P < 0.05).@*CONCLUSION@#AE knockdown results in differential expressions of m6A-associated enzymes, suggesting that the AE fusion gene regulates the expression of one or more m6A-associated enzymes to control cellular methylation levels.

Research advances on the promotive healing effect of hydrogel dressing for diabetic foot wound / 中华烧伤杂志

In recent years, the number of diabetic patients has gradually increased, and the number of patients with diabetic foot has also increased. Diabetic foot has a high rate of disability and death, seriously affects the patients' quality of life, shortens life expectancy, and brings heavy social burden. The current treatment methods for diabetic foot are insufficient. The concepts and methods of tissue engineering provide new thoughts and means for the treatment of diabetic foot. This article introduces the pathogenesis of diabetic foot wounds, the factors leading to non-healing of diabetic foot, the applications of functional hydrogel dressings in the treatment of diabetic foot and their technical methods of functional hydrogel dressings for treating skin wounds in diabetic animals, and the future development direction of functional hydrogel dressing for treating diabetic foot wounds is prospected.

Analysis of influenza prevalence among children in Jinshan District of Shanghai from 2010 to 2019 / 上海预防医学

Objective To analyze the epidemic characteristics of influenza in children in Jinshan District of Shanghai，so as to provide scientific basis for prevention and control of influenza in children. Methods We analyzed the surveillance data as well as the results of virus isolation and identification in children with influenza-like illness （ILI） in Jinshan District of Shanghai from January 2010 to December 2019. Results There were two annual epidemic peaks in 2010， 2016， 2017 and 2018， one annual epidemic peak in winter and spring in 2011 and 2013， and two annual epidemic peaks in 2012， 2014， 2015 and 2019. A total of 3 859 ILI cases were collected in the past 10 years， and 848 positive virus strains were isolated， with a positive rate of 21.97%. Among them， 371 were seasonal H3N2， 163 were new H1N1， 314 were type B（among them， 226 were yamagata and 88 were victoria）. The positive rates of influenza virus in different children groups were 0.88% in scattered children， 6.76% in kindergarten children， and 14.33% in students， respectively （P= 0.001）. Conclusion From January 2010 to December 2019， seasonal H3N2 was the predominant virus strain in children influenza epidemic in Jinshan District of Shanghai. The influenza epidemic shows a strong seasonal feature with double peaks in winter/spring， summer or autumn. The positive rate of influenza virus in middle school students is the highest in different age groups， followed by kindergarten children.

Effect of acupuncture for dysphagia after stroke based on fiberoptic endoscopic swallowing function evaluation / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture combined with regular treatment and swallowing function training on pharyngeal motor, sensory function and penetration-aspiration function in patients with dysphagia after stroke.@*METHODS@#A total of 60 patients with dysphagia after stroke were randomly divided into a control group and an observation group, 30 patients in each group. Both groups were treated with conventional treatment and swallowing function training; in addition, the observation group was treated with acupuncture at Lianquan (CV 23), Fengfu (GV 16), Yifeng (TE 17). All the treatments were given once a day, 5 days a week, for totally 4 weeks. In the two groups, the pharyngeal motor and sensory function, penetration-aspiration scores were evaluated by fiberoptic endoscopic evaluation of swallowing (FEES), and the Kubota water swallowing test scores were assessed before and after treatment, and the clinical effects were compared.@*RESULTS@#After treatment, the pharyngeal motor and sensory function in the two groups were all higher than those before treatment (P<0.05), and those in the observation group were better than the control group (P<0.05). After treatment, the penetration-aspiration scores and Kubota water swallowing test scores in the two groups were all lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, which was better than 73.3% (22/30) in the control group (P<0.05).@*CONCLUSION@#Acupuncture combined with regular treatment and swallowing training could improve the pharyngeal motor and sensory function, and penetration-aspiration scores in patients with dysphagia after stroke.

Effect of Diabetes-Mediated Pericyte Injury on Blood-Spinal Cord Barrier Destruction after Spinal Cord Injury / 中国生物化学与分子生物学报

Diabetes mellitus (DM) is a common and chronic metabolic disease, which disturbs the internal environment, and then causes series of acute or chronic complications. Chronic hyperglycemia induces macroangiopathy and microangiopathy, which is synergistically regulated by intricate molecular mechanisms, including inflammatory responses, intracellular stress, pyrotosis and ferroptosis. DM hinders the repair of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) and aggravates the neurological damage. Pericytes are the main component of neurovascular units, which regulates angiogenesis, capillary blood flow, and BSCB permeability. After SCI, the BSCB is destroyed, the coverage rate of pericytes is significantly reduced. Then, it greatly affects the normal function of blood vessels. Diabetes not only plays a role in regulating the contraction phenotype and signal transduction of pericytes, but also changes the secretion genome spectrum of pericytes, and then affects the normal function of pericytes. Moreover, it has also been shown that diabetes promotes the loss of pericytes after SCI. This review systematically describes the regulatory effect of diabetes on pericytes in the vascular system, and the effect of diabetes mediated-pericyte injury on BSCB after SCI.

Effects of DREADD-mediated inhibition of glutamatergic neurons in PVN on myocardial ischemia-reperfusion injury in mice / 中国药理学通报

Aim To explore the effeet of chemogenetic designer reeeptors exclusively activated by designer drugs( DREADD) mediated inhibition of glutamatergic neurons in paraventricular nucleus of hypothalamus (PVN ) on myocardial ischemia-reperfusion injury in mice.Methods Mice were catheterized in PVN by stereotaxic technique, followed by recover}' for three days in individual cages.The mice were then received the inhibitory virus rAAV CaMK E cx-hM4d (Gi)-EG- FP-WPRE-hGHpA or the control vims rAAV CaMK H a - E GF P- W PRE - h GH pA in the PVN nucleus.Three weeks after virus infection, myocardial ischemia-reperfusion injury ( IR) was performed by ligating the left anterior descending coronary artery for 1 h and then releasing it for 2 h.Clozapine N-oxide (CNO) 2 mg •kg 1 was injected intraperitoneally 1 h before IR, to induce inhibition of glutamatergic neurons in PVN by specifically binding to the hM4D receptor ( Gi).TTC staining was used to measure the infarct size, and ELISA was used to measure the serum cTnl concentration.During experiments, the ECG was recorded by PowerLab system.Western blot was used to detect the pro-survival kinase ERK and cleaved caspase-3 proteins in heart tissues, and the expressions of EGFP, CaMKII and c-fos in PVN were examined under fluorescence microscope.Results The glutamatergic neurons in PV N were specifically infected by AAV vectors.When compared with sham group, the ratio of IS/AAR, serum cTnl, c-fos in PVN, and cleaved caspase-3 protein all increased in IR group , but the pERK level decreased.However, hM4D ( Gi) DREADD mediated inhibition of PVN glutamatergic neurons significantly reduced IS/AAR, cTnl concentration and c-fos expression in PVN, as well as the decrease of cleaved caspase-3 and the increase of pERK in heart tissues.Conclusion Chemogenetic DREADD mediated inhibition of glutamatergic neurons in paraventricular nu- cleus of hypothalamus ( PVN) reduces myocardial is- chemia-reperfusion injury in mice.

Effects of lysophosphatidic acid on ischemia/reperfusion injury and TRPV1 expression in isolated mouse heart / 中国药理学通报

Aim To investigate the effects of lysophosphatidic acid on ischemia / reperfusion injury(IRI)and TRPV1 expression in isolated mouse heart.Methods The IRI model of isolated mouse heart was established by Langendorff device.The hearts in sham group were continuously perfused for 100 min.The hearts in IR group were stabilized for 10 min followed by no perfusion for 30 min and reperfusion for 60 min.Exogenous LPA was added in the K-H solution during IR in IR+LPA group while HA130, an LPA synthesis inhibitor, was intraperitoneally injected before IR in IR+HA130 group.The infarct volume was measured by TTC staining, the determination of LPA and LDH levels in coronary effluent and LPA concentration in serum was measured by ELISA method.Finally, the expression levels of pTRPV1/TRPV1 and Bcl-2/Bax in myocardial tissues were determined by Western blot.Results Compared with sham group, IR caused evident myocardial infarction and increased the levels of LDH and LPA in coronary effluent.The increase of LPA was linearly correlated with myocardial infarction volume.In addition, the protein levels of pTRPV1 and TRPV1 in myocardium increased, while the ratio of Bcl-2/Bax decreased.The myocardial injury in IR+LPA group was aggravated.In contrast, myocardial IRI was reversed in IR+HA130 group.Conclusions Myocardial ischemia-reperfusion induces the release of LPA, which aggravates myocardial post-ischemic injury, while the inhibition of LPA release exerts cardioprotective effects.The underlying mechanisms might be related to the regulation on cardiac TRPV1 expression and apoptotic signals.

Effect of NBED on decorporation of uranium and protective effect on HK-2 cellular damage / 中国药理学通报

Aim To study the effect of NBED on the decorporation of uranium and the protective effect on HK-2 cellular damage.Methods ICR mice were divided into control group, uranium exposure group(0.03 mg), DTPA-CaNa3(300 mg·kg-1)and NBED(300, 150, 75 mg·kg-1)treatment groups.After injection of uranyl acetate, mice were given different doses of decorporation agents immediately.After 24 h the content of uranium in kidney, bone, liver, spleen and muscle was determined by ICP-MS.HK-2 cells were divided into control group, uranium model group(80 μmol·L-1), DTPA-CaNa3(80 μmol·L-1)and NBED(80, 40, 20 μmol·L-1)treatment group interacted with uranium for 48h.CCK-8 method was used to detect the cell survival rate; light microscope was used to observe the cell morphology; ICP-MS method was used to detect the ratio of uranium endocytosis and uranium efflux; biochemical method was employed to determine SOD, GSH and LDH levels; flow cytometry was applied to determine ROS, apoptosis and cell cycle.Results 300 mg·kg-1 NBED reduced the content of uranium in kidney and bone by 44.3% and 18.8% respectively.Compared with model group, NBED reduced uranium entry into cells by 11%42%, increased uranium emission by 18%48%, increased the survival rate of HK-2 cells, thelevels of SOD and GSH, decreased the expression levels of ROS and LDH, and decreased the apoptotic rate and S phase arrest.DTPA-CaNa3 could significantly reduce the content of uranium and the amount of uranium endocytosis in kidney of mice, but the effect of promoting excretion was significantly lower than that of NBED, and it had no protective effect on the acute injury of HK-2 cells caused by uranium.Conclusions NBED is an effective uranium decorporation agent, which is superior to DTPA-CaNa3 approved by FDA.It could reduce the production of ROS and LDH, increase the content of SOD and GSH, and reduce the arrest and apoptosis of S phase, thus protecting HK-2 cells from uranium induced damage.

Systematic chemical characterization of Xiexin decoctions using high performance liquid chromatography coupled with electrospray ionization mass spectrometry / 中国天然药物

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

Characterization of the chemical constituents of Jie-Geng-Tang and the metabolites in the serums and lungs of mice after oral administration by LC-Q-TOF-MS / 中国天然药物

Jie-Geng-Tang (JGT), a traditional formula, is employed in the treatment of sore throat and cough and comprises Platycodonis Radix and Glycyrrhizae Radix et Rhizoma in the ratio 1 : 2. Our previous study demonstrated that JGT protected mice from S. aureus-induced acute lung injury (ALI). Five constituents of JGT showed antibacterial activities against S. aureus in vitro. However, the potential effective constituents of JGT in vivo were still unclear. In this study, the chemical constituents of JGT were identified by liquid chromatography with quadrupole time-of-flight spectrometry (LC-Q-TOF-MS). A total of 96 constituents were identified or assumed, including seven organic acids, 45 flavonoids, 36 triterpene saponins, and eight compounds of other types. The structures of 31 of the constituents were confirmed by comparing them with corresponding authentic standards. Moreover, 15 prototypes and 49 metabolites were deduced in the serums of mice, 24 prototypes and 47 metabolites were deduced in the lungs of mice after the oral administration of JGT. Three types of constituents, namely organic acids, flavonoids, and triterpene saponins, could be absorbed into the blood. Moreover, flavonoids and triterpene saponins were more likely distributed in the lung than in the blood. To the best of our knowledge, this is the first report on the systematic metabolites profile of JGT in vivo. The results reported were beneficial to the elucidation of the effective material basis of JGT.