Value of rifampicin-resistant real-time fluorescence quantitative nucleic acid amplification detection technology in the fast diagnosis of pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To evaluate the value and significance of rifampicin-resistant real-time fluorescence quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in the diagnosis of pulmonary tuberculosis. 　　Methods　The clinical data of 228 patients with suspected pulmonary tuberculosis, who admitted to Hebei Chest Hospital from January 2018 to December 2019, were analyzed retrospectively. The sputum was collected for GeneXpert MTB/RIF, sandwich cup liquid-based bacterial acid-fast staining smear microscopy (referred to as “sandwich cup method”) and Loop-Mediated isothermal amplification (referred to as “LAMP method”) and the results were statistically analyzed by SPSS 17.0 software. Results　Among the 228 patients with suspected cases, 200 cases were clinically diagnosed as pulmonary tuberculosis and 28 were non-tuberculosis. The positive detection rate of GeneXpert MTB/RIF (81.0%, 162/200) was significantly higher than that of sandwich cup method (62.5%, 125/200) and LAMP method (72.5%,145/200) (χ2=16.885, 4.049, P<0.05). Taking clinical diagnosis as gold standard, the sensitivity of GeneXpert MTB/RIF (80.00%,160/200) was significantly higher than that of sandwich cup method (60.00%, 120/200) and LAMP method (70.50%, 141/200) (χ2=19.048, 4.846, P<0.05). The diagnostic consistency of GeneXpert MTB/RIF (K=0.73) was higher than that of sandwich cup method (K=0.39) and LAMP method (K=0.56). Conclusions The GeneXpert MTB/RIF detection method is rapid and simple, and can diagnose pulmonary tuberculosis rapidly and simultaneously detect rifampicin resistance of Mycobacterium tuberculosis with high sensitivity. It has high clinical value for early diagnosis of pulmonary tuberculosis and guidance of treatment in general and specialized hospitals.

Maxent modeling for predicting the global potential distribution of talaromycosis marneffei / 中国热带医学

@#Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-β axis / 中西医结合学报

OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.@*METHODS@#Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.@*RESULTS@#The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.@*CONCLUSION@#The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.

Investigation and influencing factors on pelvic floor muscle strength of 929 adult females in gynecological outpatient department / 中华妇产科杂志

Objective: To investigate the present situation of pelvic floor muscle strength, and to analyze the factors affecting pelvic floor muscle strength. Methods: The data of patients who were admitted into the general outpatient department of gynecology, Peking University People's Hospital from October 2021 to April 2022 were collected, and the patients who met the exclusion criteria were included in this cross sectional study. The patient's age, height, weight, education level, defecation way and defecation time, birth history, maximum newborn birth weight, occupational physical activity, sedentary time, menopause, family history and disease history were recorded by questionnaire. Morphological indexes such as waist circumference, abdomen circumference and hip circumference were measured with tape measure. Handgrip strength level was measured with grip strength instrument. After performing routine gynecological examinations, the pelvic floor muscle strength was evaluated by palpation with modified Oxford grading scale (MOS). MOS grade>3 was taken as normal group and ≤3 as decreased group. Binary logistic regression was used to investigate the related factors of deceased pelvic floor muscle strength. Results: A total of 929 patients were included in the study, and the average MOS grade was 2.8±1.2. By univariate analysis, birth history, menopausal time, defecation time, handgrip strength level, waist circumference and abdominal circumference were related to the decrease of pelvic floor muscle strength (all P<0.05). By binary logistic regression analysis, the level of handgrip strength (OR=0.913, 95%CI: 0.883-0.945; P<0.001) was correlated with normal pelvic floor muscle strength; waist circumference (OR=1.025, 95%CI: 1.005-1.046; P=0.016), birth history (OR=2.224, 95%CI: 1.570-3.149; P<0.001), sedentary time> 8 hours (OR=2.073, 95%CI: 1.198-3.587; P=0.009) were associated with the decrease of pelvic floor muscle strength. Conclusions: The level of handgrip strength is related to the normal pelvic floor muscle strength of females, while the waist circumference, birth history and sedentary time>8 hours are related to the decrease of pelvic floor muscle strength of females. In order to prevent the decrease of pelvic floor muscle strength, it is necessary to carry out relevant health education, enhance exercise, improve the overall strength level, reduce daily sedentary time, maintain symmetry, and carry out comprehensive overall intervention to improve pelvic floor muscle function.

Establishment of a recombined mannose-binding lectin protein-magnetic beads-enriched binding recombinant enzyme-assisted polymerase chain reaction assay for Candida in blood samples / 中华流行病学杂志

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.

Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children.@*METHODS@#Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed.@*RESULTS@#The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024).@*CONCLUSIONS@#JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks / 法医学杂志

OBJECTIVES@#The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI.@*METHODS@#The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in.@*RESULTS@#Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid.@*CONCLUSIONS@#ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells / 中国中药杂志

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Fibroblast growth factor 23 and cerebrovascular diseases / 国际脑血管病杂志

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in the regulation of calcium, phosphorus and active vitamin D levels. Recent studies have shown that high FGF23 is associated with cardiocerebrovascular diseases. This article reviews the correlation between FGF23 and cerebrovascular diseases.

Effect of altitude hypoxia on blood-brain barrier after subarachnoid hemorrhage based on phosphatidylinositol 3-kinase/protein kinase B/nuclear factor κB pathway in rats / 解剖学报

Objective To investigate the effect of plateau hypoxia on the blood-brain barrier after subarachnoid hemorrhage (SAH) in rats. Methods Adult male SD rats (n = 78) were randomly divided into 4 groups: sham group (sham), SAH model group (SAH), plateau hypoxia sham group (Hp sham) and plateau hypoxia SAH model group (Hp SAH). The rat model of plateau hypoxia was established through low-pressure simulation chamber (altitude 5000 m), and the SAH model was established by endovascular perforation method. At 24 hours after SAH, neurobehavior score and SAH grade were assessed. The morphological changes of neurons and apoptosis of nerve cells in the CA1 region of hippocampal were observed by the staining of Nissl and TUNEL. The expression of phosphorylated PI3K (p-PI3K), PI3K, phosphorylated Akt (p-Akt), Akt, phosphorylated nuclear factor κB (p-NF-κB), NF-κB, matrix metalloproteinase-9 (MMP-9), occludin and claudin-5 in hippocampal were detected by the method of Western blotting. The expression of occludin and claudin-5 proteins in the CA1 region of hippocampal were observed by immunofluorescent staining. Results At 24 hours after SAH, the neurobehavior score decreased significantly and SAH grade increased significantly in the SAH and Hp SAH group (P< 0.05). Neurobehavior score decreased significantly in the Hp SAH group compared with the SAH group (P < 0.05). In the SAH group, neurons in the CA1 region of hippocampus were atrophied and deformed, the arrangement were disordered, the number of neurons decreased significantly, and the apoptosis of nerve cells increased significantly(P< 0.05). Plateau hypoxia could aggravate the morphological damage of neurons and apoptosis of nerve cells. The expression of p-PI3K/PI3K, p-Akt/Akt, occludin and claudin-5 proteins decreased significantly, while the expression of p-NF-κB/NF-κB and MMP-9 proteins increased significantly in the SAH and Hp SAH group (P< 0.05). The expression of p-PI3K/PI3K and MMP-9 proteins increased significantly in Hp SAH group compared with the SAH group. The expression of claudin-5 protein increased significantly in Hp sham group compared with the sham group (P < 0.05). Immunofluorescent staining showed that the expression of occludin and claudin-5 proteins in the CA1 region of hippocampus decreased in the SAH group. Plateau hypoxia could further decreased the expression of occludin and claudin-5 proteins. Conclusion Plateau hypoxia aggravates blood-brain barrier disruption after subarachnoid hemorrhage in rats through inhibiting PI3K/Akt/NF-κB pathway.

Effects of hypoxia preconditioning on hematology-related indexes through hypoxia inducible factor-1α/ stromal cell-derived factor-1 pathway in rats / 解剖学报

[Abstract] Objective To study the role of hypoxia inducible factor-1α (HIF-1α) / stromal cell-derived factor-1 (SDF-1) pathway in high altitude hypoxia preconditioning in rat. Methods Seventy-six adult male SD rats, which through fed in low-pressure oxygen chamber (altitude 5000 m) and Xining (altitude 2260 m) to establish the rat model of hypoxia preconditioning. Rats randomly divided into 6 groups: control group (Ctrl), high altitude hypoxic preconditioning 1 day group (HHP-1d), high altitude hypoxic preconditioning 4 days group (HHP-4d), high altitude hypoxic preconditioning 15 days group (HHP-15d), high altitude hypoxic preconditioning 30 days group (HHP-30d), medium altitude hypoxic preconditioning group (MHP). 7. 0 T small animal MRI was used to observe the intracranial structure, diameter of basilar artery and cerebral blood flow in the hippocampus and brainstem regions by the sequences of T2 weighted images (T2WI) and arterial spin labeling (ASL) in the groups of Ctrl, HHP-4d, HHP-30d and MHP. In each group, blood routine was tested, the concentrations of HIF-1α, SDF-1 in serum, platelet activating factor (PAF)and P-selectin (SELP) in plasma were detected by the method of ELISA. Results In the hypoxia preconditioning groups, intracranial structure and diameter of basilar artery had no significant difference, while cerebral blood flow in the regions of brainstem and hippocampus increased significantly (P<0. 05). Meanwhile, red blood cell and white blood cell increased significantly, while platelet decreased significantly in the groups of hypoxia preconditioning (P<0. 05). Red blood cell and platelet in MHP group were closer to Ctrl group. The concentrations of HIF-1α and SDF-1 (except HHP-1d group) increased significantly in hypoxia preconditioning groups (P<0. 05).The concentrations of PAF and SELP increased significantly in HHP-1d and HHP-15d groups. The concentration of PAF decreased significantly in the HHP-4d and HHP-30d groups, and SELP decreased significantly in HHP-4d group (P<0. 05). Conclusion Hypoxia preconditioning can increase oxygen storage and immune defense capacity, improve brain reserve capacity and play the effect of brain protection through HIF-1α/ SDF-1 pathway. The best effect preconditioning was feed at medium altitude (altitude 2260 m) for 30 days.

Effects of Zishen Huoxue Prescription on OGD/R-induced mitophagy in hippocampal neurons / 中国药理学通报

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis / 中华肿瘤杂志

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

Effect of thimerosal on vaccine antigen activity and its mechanism / 中国生物制品学杂志

@#Abstract： Thimerosal is commonly used as a preservative in biological products，especially in vaccines. Although it has been removed from single ⁃ dose vaccines in most countries，thimerosal is still widely used in multi ⁃ dose vaccines at present. Thimerosal，as a component in vaccine preparation，should be compatible with other components，especially should not damage the activity of antigen. However，in recent years，many studies have reported that thiomersal can reduce the antigenicity and immunogenicity of vaccine antigens，especially protein antigens containing or rich in cysteine（Cys）， suggesting that the effect of thimerosal on vaccine antigen activity should be fully evaluated when it is used as a vaccine preservative. In this paper，the effects of thimerosal on antigenicity and immunogenicity of two inactivated vaccines and three recombinant protein vaccines and the possible mechanisms were reviewed，in order to provide reference for rational selection of vaccine preservatives.

Effects of upper limb exergames on functional recovery in stroke patients with mild cognitive impairment / 中国康复理论与实践

ObjectiveTo explore the effects of upper limb exergames on cognitive function, upper limb motor function and activities of daily living in stroke patients with mild cognitive impairment. MethodsFrom August, 2020 to November, 2021, 50 troke patients with mild cognitive impairment in Beijing Bo'ai Hospital were randomly allocated to control group (n = 25) and experimental group (n = 25). Both groups received traditional occupational therapy. Additional functional occupational therapy was provided to the control group, and upper limb exergames were provided to the experimental group, for four weeks. They were assessed with Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after the treatment. ResultsAfter treatment, the scores of MoCA, FMA-UE and MBI improved in both groups (|t| > 3.354, |Z| > 4.379, P < 0.01), and the scores increased in five MoCA cognitive domains in the control group (except map naming and abstract thinking) (|Z| > 2.000, P < 0.05) and in six MoCA cognitive domains in the experimental group (except map naming) (|Z| > 2.646, P < 0.01). After treatment, the scores of MoCA, MoCA five cognitive domains (except map naming and abstract thinking) and FMA-UE were better in the experiment group than in the control group(|Z| > 1.982, t = 3.565, P < 0.05). ConclusionUpper limb exergames can facilitate the recovery of cognitive function, upper limb motor function and activities of daily living in stroke patients with mild cognitive impairment.

Clinical diagnosis and prognostic value of serum TLR4 and VEGFA expression in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and clinical significance of Toll-like receptor 4(TLR4)and vascular endothelial growth factor A(VEGFA)in the serum of patients with diabetic retinopathy(DR).METHODS: A total of 183 patients with type 2 diabetes mellitus(T2DM)admitted to our hospital from January 2021 to January 2022 were collected as the study subjects. They were grouped into non diabetic retinopathy(NDR)group(n=54), proliferative diabetic retinopathy(PDR)group(n=68)and non proliferative diabetic retinopathy(NPDR)group(n=61). In the same period, 70 volunteers who underwent physical examination in our hospital were randomly stratified according to age and sex. After discharge, DR patients were followed up for 1a and grouped into a poor prognosis group(n=40)and a good prognosis group(n=89)based on whether they had visual impairment. Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of TLR4 and VEGFA in serum; Logistic regression was applied to analyze the influencing factors of DR; receiver operating characteristic(ROC)curve was applied to analyze the clinical value of serum TLR4 and VEGFA levels in diagnosing DR and predicting prognosis.RESULTS: There were statistical significance in TLR4 and VEGFA levels among the control group, NDR group, PDR group, and NPDR group(F=935.753, 516.936, all P&#x003C;0.05), and further pairwise comparisons showed statistical significance(P&#x003C;0.05); the expression levels of TLR4 and VEGFA in the serum of patients with poor prognosis were higher than those of patients with good prognosis(P&#x003C;0.01); the results of Logistic regression analysis showed that TLR4, VEGFA, course of disease, and HbA1c were all risk factors for the occurrence of DR(P&#x003C;0.05); the ROC results showed that the AUC of serum TLR4, VEGFA levels, and their combination for predicting DR was 0.869, 0.862, and 0.931, respectively, the AUC of serum TLR4, VEGFA levels, and their combined prediction of visual disability in DR patients was 0.864, 0.863, and 0.938, respectively.CONCLUSION: The expression of TLR4 and VEGFA in serum of DR patients is up-regulated, and the combined detection of TLR4 and VEGFA can be used as a potential indicator to evaluate the occurrence and poor prognosis of DR.

The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.@*METHODS@#The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.@*RESULTS@#Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.@*CONCLUSION@#The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy / 中国当代儿科杂志

OBJECTIVES@#To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora.@*METHODS@#Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy.@*RESULTS@#The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05).@*CONCLUSIONS@#The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.