Research progress of anti-pulmonary fibrosis drugs targeting autotaxin-lysophosphatidic acid axis / 药学学报

Pulmonary fibrosis is an interstitial lung disease characterized by inflammatory injury and tissue structure destruction. Currently, there is a lack of effective therapeutic drugs for pulmonary fibrosis, and the mechanism is still unknown. Therefore, it is urgent to seek new targets for effective drugs. In pulmonary fibrosis, the level of autotaxin (ATX) in bronchoalveolar lavage fluid increases and stimulates the production of lysophosphatidic acid (LPA). The involvement of LPA receptors in activating a variety of G-protein-mediated signal transduction pathways leads to a range of related physiological effects, including pro-inflammatory signaling in epithelial cells, activation of transforming growth factor signaling, and stimulation of fibroblast accumulation. LPA receptor antagonists and ATX inhibitors have been concerned as new targets for pulmonary fiber therapy, and currently related drugs have entered clinical trials. In this paper, the pathophysiological effects of LPA and ATX in pulmonary fibrosis disease and related drug development progress were reviewed to provide reference information of new drug development for pulmonary fibrosis based on the ATX-LPA axis.

Establishment of a nomogram model for predicting necrotizing enterocolitis in very preterm infants / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC.@*METHODS@#A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model.@*RESULTS@#The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value.@*CONCLUSIONS@#Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.

Mouse Model of Cisplatin Induced Ototoxicity / 中山大学学报(医学科学版)

@#【Objective】To establish a reliable and reproducible mouse model of cisplatin induced inner ear hair cells loss and to make possible for further study of mechanisms of cisplatin-induced ototoxicity in mice from the molecular and genetic aspects. 【Methods】Twenty healthy mice were evenly divided into two groups in random. The mice in group A received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（1.0 mg/kg，intraperitoneal）1 h later，and the mice in group B received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（0.5 mg/kg，intraperitoneal）1 h later. Auditory brainstem response（ABR）and distortion product otoacoustic emission （DPOAE） were tested in both groups 10 d post the cisplatin-furosemide treatment and bilateral cochlea were taken out and fixed，one side cochlea were used for the surface preparation of total cochlear basal membrane and stained to count the number of cochlear hair cells from apex to base，the other was embedded with EPON 812 gel and then cut into half thin slices. Six mice were used as control group. 【Results】In both groups，the average ABR threshold of mice at each frequency were elevated，while the average DPOAE values were decreased. The average ABR threshold in group A increased significantly and the amplitude of each frequency decreased a lot，and DPOAE in high frequencies vanished；In group B，there was a minor elevation of ABR threshold with a slightly lower amplitude in higher- frequencies（16，20，32 kHz）but no amplitude change in lower frequencies（4，8，12 kHz）both in ABR and DPOAE. The surface preparation of Cochlear results in group A showed that nearly all the outer hair cells in the base had been destroyed，and most were destroyed in the apex；In group B，only the majority of cochlear outer hair cells at the base missed. There was no decrease of the numbers of the inner hair cells in both groups. Semi-thin cross-sections results also showed that the stria vascularis and spiral ganglion cells were close to normal in both groups. 【Conclusion】Co- administration of single dose of 1.0 mg/kg cisplatin with a single dose of 200 mg/kg furosemide may induce significant loss of cochlear outer hair cells in mice.

High-frequency ultrasonography for diagnosis and differential diagnosis of acute scrotum in children / 中华男科学杂志

<p><b>Objective</b>To analyze the high-frequency ultrasound image features of acute scrotum in children and explore the value of high-frequency ultrasonography in the diagnosis and differential diagnosis of the disease.</p><p><b>METHODS</b>This retrospective study included 256 children aged 2 days to 14 years undergoing color Doppler ultrasonography at 2 hours to 3 days after onset of acute scrotum. We analyzed the morphology, internal echo and blood supply of the testis in comparison with the clinical and pathological results.</p><p><b>RESULTS</b>Among the 256 cases, acute testicular torsion was found in 23, of which 16 were treated by complete resection the necrotic testis and the other 7 by surgical reduction of testicular torsion. Ultrasonographically, the involved testes presented different degrees of increase or decrease in volume, with uneven internal echoes, irregular hypoechoic flakes, and testicular hydrocele. Color Doppler flow imaging (CDFI) showed significant blood flow signals around the diseased testes but none within them. Acute testicular appendix torsion was found in 116 cases, in which ultrasonography manifested nodules with round or oval abnormal echoes between the upper pole of the testis and caput epididymidis, first hypoechoic and then gradually increased, heterogeneous internally. CDFI revealed enlarged epididymides and enriched testicular blood flow but no blood flow signals in the nodules. The 103 cases of acute epididymitis were ultrasonographically characterized by varied degrees of swelling of the involved epididymis with uneven internal echoes and rich blood flow signals on CDFI. Six of the cases were diagnosed as acute orchitis, with the ultrasonographic features of testicular swelling and low but uniform internal echoes, with rich blood flow signals on CDFI. Incarcerated inguinal hernia was confirmed in 15 cases, in which ultrasonography revealed intrusion of the hernia into the obviously enlarged scrotal sac with the mesentery and intestine in it, and blood flow visible on CDFI. Acute scrotal wall hematoma and edema was found in 8 cases, with the ultrasonographic characteristics of scrotal wall thickening, with visible blood flow signals on CDFI.</p><p><b>CONCLUSIONS</b>High-frequency ultrasonography has a high sensitivity and specificity for acute scrotum in children, which can be applied as the first-choice clinical imaging modality and provide reliable evidence for the diagnosis and differential diagnosis of the disease.</p>

Paternally originated Wolf-Hirschhorn syndrome detected by multiplex ligation-dependent probe amplification and microarray comparative genomic hybridization / 中华儿科杂志

<p><b>OBJECTIVE</b>To confirm the diagnosis of a Wolf-Hirschhorn syndrome by family study using both cytogenetic and molecular genetic techniques.</p><p><b>METHOD</b>G-band karyotyping was performed for all the 6 members in the family. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the chromosome abnormality for the proband, his father and brother. Microarray comparative genomic hybridization (Array-CGH) was carried out to map the exact chromosomal breakpoints for the proband.</p><p><b>RESULT</b>The proband presented with a typical face, delayed growth and hypotonia in Wolf-Hirschhorn syndrome. His G-band karyotype was 46, XY, der(4)t(4;8) (p16.2; p23.1)pat. MLPA showed 4pter loss and 8pter gain. Array-CGH revealed an XY male with a 3.781 Mb deletion of 4p16.3-p16.2 and a 6.760 Mb duplication of 8p23.3-p23.1. The proband's brother has mental retardation and skeletal abnormalities. His G-band karyotype was 46, XY, der(8)t(4;8)(p16.2;p23.1)pat. MLPA showed 4pter gain and 8pter loss. The proband's father had normal phenotype with a balanced translocation of 46, XY, t(4;8)(p16.2;p23.1)pat. MLPA showed a normal result. The proband's grandfather showed a normal phenotype with a balanced translocation 46, XY, t(4;8)(p16.2;p23.1). The other members in the family showed normal phenotypes with normal karyotypes.</p><p><b>CONCLUSION</b>The proband has features of Wolf-Hirschhorn syndrome with partial monosomy 4p and partial trisomy 8p. The proband's brother has a partial trisomy 4p and partial monosomy 8p. The derived chromosomes are inherited from paternal balanced translocation t(4;8)(p16.2;p23.1).</p>

Clinical and experimental study of 7 cases of acute lymphoblastic leukemia with dic(7;9) (pll;pll) / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the laboratory and clinical features of 7 cases of acute lymphoblastic leukemia (ALL) with dic(7;9) (pll;pll).</p><p><b>METHODS</b>Cytogenetic examination of bone marrow cells was performed by direct method or short-term culture method. R banding technique was used for karyotype analysis. bcr/abl fusion gene was detected by interphase FISH using dual-color bcr/abl probe in 6 cases. FISH using chromosome 7-specific alpha-satellite DNA probe and chromosome 9-specific alpha-satellite DNA probe and chromosome painting using whole chromosome 7 and 9 paints probes were performed respectively.</p><p><b>RESULTS</b>Seven (0.88%) of 800 ALL patients were found to have dic(7;9) abnormality. Among them, dic(7;9) was the sole abnormality in 2 cases, t(9;22), other additional aberrations besides dic(7;9) in 4 cases and dic (7;9) with other abnormalities but no t(9;22) in one case. Hyperleukocytosis (> 100 x 10(9)/L) was found in 4 cases with dic(7;9) and t(9;22), and patients without t(9;22) had WBC < 100 x 10(9)/L. Enlargement of liver, spleen and/or lymph nodes were found in 6 cases. Immunophenotyping showed that 5/6 cases of dic (7;9) ALL were of B lineage. Dual-color FISH detected bcr/abl rearrangement in 3/6 cases and confirmed that the centromere of the derivative chromosome was originated from both chromosomes 7 and 9. A reciprocal translocation between chromosomes 7 and 9 was proved by chromosome painting.</p><p><b>CONCLUSION</b>dic(7;9) was a rare, but recurrent chromosome abnormality in ALL and had some clinical and laboratory features.</p>

Genomic abnormalities detected by panel fluorescence in situ hybridization in chronic lymphocytic leukaemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the value of panel fluorescence in situ hybridization for detection of genomic aberrations in chronic lymphocytic leukemia(CLL).</p><p><b>METHODS</b>Five types of fluorescein-labelled DNA probes including centromeric probes for chromosomes 3,12 and 18, and two sequence-specific probes D13S272 for 13q14.3 and ATM for 11q23 were used to perform fluorescence in situ hybridization (FISH) assays in 22 patients with CLL. Its results were compared with that of conventional cytogenetic (CC) examination in order to ascertain which method is more sensitive and reliable for the detection of chromosomal and genomic abnormalities in CLL.</p><p><b>RESULTS</b>On CC examination, only 8 cases (36.3%) were found to have chromosomal abnormalities including sole trisomy 12 in 3 cases, simultaneous trisomies 3 and 12 in one case, simultaneous trisomies 3, 12 and 18 in one case, translocation between chromosomes 5 and 15 in one case, deletion of 13q14.3 in one case, 3q- and 18p+ in one case, 4q+ and 13q- in one case, whereas on panel FISH assay, 15 cases (68.1%) were found to have genomic aberrations including trisomy 3 in 4 cases, trisomy 12 in 6 cases, trisomy 18 in one case, deletion of 13q14.3 in 8 cases, deletion of 11q23 in 6 cases.</p><p><b>CONCLUSION</b>Panel FISH is a useful method for detection of genomic aberration in CLL, if combined with CC, it can obviously enhance the detection rate of chromosomal abnormalities in CLL.</p>

Application of reverse transcription-multiplex nested PCR to detect MLL rearrangement in AML-M4/M5 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of reverse transcription-multiplex nested PCR in detecting MLL rearrangement in lzAML-M4/M5.</p><p><b>METHODS</b>Bone marrow chromosome preparation was made using direct method or short-term culture. Karyotypic analysis was carried out by R-banding technique. Five common MLL fusion genes and MLL partial tandem duplication in 40 AML cases, including 12 M4 and 28 M5 were detected by reverse transcription(RT)-multiplex nested PCR.</p><p><b>RESULTS</b>R-banding karyotypic analysis revealed 11q23 translocation including t(6;11)(q27;q23), t(9;11)(p21;q23), t(11;17)(q23;q21) and t(11;19)(q23;p13.1) in 7 cases. MLL rearrangements consisting of MLL/AF6 (1 case), MLL/AF9 (1 case), MLL/AF17 (2 cases), MLL/ELL (2 cases) and MLL partial tandem duplication(2 cases) were detected in 8 cases by RT-multiplex nested PCR. Among 8 cases with MLL rearrangement, 6 were chromosome translocation, 2 were MLL partial tandem duplication.</p><p><b>CONCLUSION</b>RT-multiplex nested PCR is a powerful technique in the detection of MLL rearrangement for tentativelly diagnosed AML-M4/M5.</p>

Study on mixed lineage leukemia gene rearrangement in AML-M4/M5 by interphase fluorescence in situ hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of fluorescence in situ hybridization (FISH) in the detection of mixed lineage leukemia (MLL) rearrangement and to assess the incidence and prognostic significance of MLL gene rearrangement in AML-M4/M5.</p><p><b>METHODS</b>Bone marrow chromosome preparation of 23 cases of acute myeloid leukemia(AML) consisting of 19 cases with M5 and 4 cases with M4 was made using direct method or short-term culture. Karyotypic analysis was carried out by R-banding technique. Dig labeled 11q23 probe which spans the breakpoint cluster region in MLL was used to detect the MLL rearrangement in the above 23 cases.</p><p><b>RESULTS</b>R-banding karyotyping analysis revealed 11q23 translocation in 7 cases, while FISH analysis detected MLL rearrangement in 12 cases including the above 7 cases.</p><p><b>CONCLUSION</b>Interphase FISH was more sensitive in detecting the MLL rearrangement in AML-M4/M5, compared with the conventional cytogenetic method. MLL rearrangement is highly related to AML-M4/M5; it is an indication of poor prognosis.</p>

Study on metronidazole resistance to Helicobacter pylori from three populations with different ethnics in Yunnan / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the prevalence of Helicobacter pylori (H.pylori) resistance to metronidazole among three populations in Yunnan.</p><p><b>METHODS</b>Susceptibilities to metronidazole among 109 H. pylori strains (33 H. pylori strains from Han, 31 H. pylori strains from Bai and 45 H. pylori strains from Naxi ethnic populations) were tested by Epsilometer test (E-test).</p><p><b>RESULTS</b>In 109 H. pylori strains, the overall metronidazole resistance rate was 67.89%. There were no significant difference in the metronidazole resistant rates of H. pylori among Han, Bai, Naxi populations Yunnan in terms of the distribution on age and upper gastroduodenal diseases. In the facet of gender, metronidazole resistant rate of H. pylori was significantly lower in Han males than in females (chi2=5.304, P=0.027), but not seen in the Bai or Naxi peoples.</p><p><b>CONCLUSION</b>Metronidazole resistance rate of H. pyloriin Yunnan was high, but no significant difference was found among Han, Bai, Naxi peoples in the province.</p>

Mutation analysis of fibroblast growth factor receptor 3 gene in an achondroplasia family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To clarify the patients' pathogenic mechanism in an achondroplasia family not according with the genetic law of autosomal dominant inheritance disease at gene level.</p><p><b>METHODS</b>Genomic DNA from peripheral blood of all members in this family was used for amplification of the exon 10 of fibroblast growth factor receptor 3(FGFR3) gene by PCR; mutation was detected by DNA sequencing and identified by restriction endonuclease MaeIII.</p><p><b>RESULTS</b>A new mutation of A to T at nucleotide 1180 was found in patients but not in unaffected members.</p><p><b>CONCLUSION</b>Combined with pedigree analysis, it was summarized that achondroplasia patients in this family might result from this new mutation.</p>