Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

OBJECTIVE: To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities. METHODS: The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups. RESULTS: A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history. CONCLUSION For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.
Female ; Fetal Diseases ; Fetus/diagnostic imaging* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Technology ; Ultrasonography, Prenatal ; Whole Exome Sequencing

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

OBJECTIVE: To analyze the characteristics of gene mutation in adult ALL and its clinical significance. METHODS: Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed. RESULTS: In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ CONCLUSION There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.
Adult ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Receptor, Notch1/genetics* ; Sequence Analysis, DNA

Objective: Investigate the clinicopathological features for secretory carcinoma of breast (SCB). Methods: The clinical data of 3 SCB cases were collected, immunohistochemical staining was performed by the streptavidin-peroxidase (SP) method to test the expression of the antibodies: ER, PR, HER-2, Ki-67, S100, CK5/6, p63, SMA, calponin, GCDFP-15, and EGFR. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: ER was focal weakly positive in case 1 and case 2 (about 5%) , and negative in case 3. PR was focal weakly positive in case 1 (about 5%) and completely negative in case 2 and case 3. Three cases showed that HER-2, SMA, calponin, GCDFP-15 were negative, while S100, CK5/6, EGFR were diffuse strongly positive. The proliferation index was nearly 15% in case 1 and case 2, and 10% in case 3. p63 was negative in mostly tumor cells of case 1, and focal positive expression in the nucleus and cytoplasm. In case 2, p63 was completely negative. However, p63 was observed positive in the cytoplasm as well as some secretory material in case 3. ETV6-NTRK3 gene fusion detection by FISH was positive in all cases. Conclusions SCB is a rare low grade triple-negative breast cancer with the unique pathomorphologic features, while its recurrent t (12; 15) (p13; q25) translocation resulting in ETV6 -NTRK3 gene fusion. It has the indolent clinical behavior and good prognosis.

Objective Investigate the clinicopathological features for secretory carcinoma of breast (SCB). Methods The clinical data of 3 SCB cases were collected, immunohistochemical staining was performed by the streptavidin?peroxidase ( SP) method to test the expression of the antibodies: ER, PR, HER?2, Ki?67, S100, CK5／6, p63, SMA, calponin, GCDFP?15, and EGFR. Fluorescence in situ hybridization ( FISH) was used to detect the ETV6?NTRK3 gene fusion. Results ER was focal weakly positive in case 1 and case 2 (about 5%) , and negative in case 3. PR was focal weakly positive in case 1 (about 5%) and completely negative in case 2 and case 3. Three cases showed that HER?2, SMA, calponin, GCDFP?15 were negative, while S100, CK5／6, EGFR were diffuse strongly positive. The proliferation index was nearly 15% in case 1 and case 2, and 10% in case 3. p63 was negative in mostly tumor cells of case 1, and focal positive expression in the nucleus and cytoplasm. In case 2, p63 was completely negative. However, p63 was observed positive in the cytoplasm as well as some secretory material in case 3. ETV6?NTRK3 gene fusion detection by FISH was positive in all cases. Conclusions SCB is a rare low grade triple?negative breast cancer with the unique pathomorphologic features, while its recurrent t (12; 15) ( p13; q25) translocation resulting in ETV6 ?NTRK3 gene fusion. It has the indolent clinical behavior and good prognosis.