Cough, progressive exertional dyspnea, and exercise limitation are the main presenting symptoms in fibrotic interstitial lung disease (F-ILD). F-ILD is usually progressive, leading to heavy disease and socioeconomic burden. In addition to the drug therapy, pulmonary rehabilitation is an important part of comprehensive treatment in F-ILD patients. In recent years, the application of pulmonary rehabilitation in F-ILD patients has attracted the attention of clinicians and society. Meanwhile, pulmonary rehabilitation has widely applicated in F-ILD patients as it is beneficial to improve their symptoms, functional exercise and quality of life. This article provides a comprehensive review of pulmonary rehabilitation in F-ILD and proposes the principles and strategies, to prevent the progression or acute exacerbation of F-ILD and improve its application in F-ILD patients.

Cough, progressive exertional dyspnea, and exercise limitation are the main presenting symptoms in fibrotic interstitial lung disease (F-ILD). F-ILD is usually progressive, leading to heavy disease and socioeconomic burden. In addition to the drug therapy, pulmonary rehabilitation is an important part of comprehensive treatment in F-ILD patients. In recent years, the application of pulmonary rehabilitation in F-ILD patients has attracted the attention of clinicians and society. Meanwhile, pulmonary rehabilitation has widely applicated in F-ILD patients as it is beneficial to improve their symptoms, functional exercise and quality of life. This article provides a comprehensive review of pulmonary rehabilitation in F-ILD and proposes the principles and strategies, to prevent the progression or acute exacerbation of F-ILD and improve its application in F-ILD patients.

Objective To investigate the level of serum uric acid in patients with diabetes insipidus (DI),summarize the clinical characteristics of central diabetes insipidus (CDI) patients with hyperuricemia (HUA),and analyze the factors affecting the level of serum uric acid in the patients with CDI. Methods The clinical data of DI patients admitted to Peking Union Medical College Hospital from 2018 to 2021 were retrospectively analyzed.The patients were assigned into a child and adolescent group (≤ 18 years old) and an adult group (>18 years old) according to their ages.The demographic and biochemical data between two groups of patients with and without HUA were compared.Spearman correlation analysis and multiple linear regression analysis were performed to analyze the correlations between serum uric acid level and other factors. Results Among the 420 DI patients,411 patients had CDI (97.9%),including 189 patients with HUA (46.0%).Thirteen (6.9%) out of the 189 CDI patients with HUA presented the disappearance of thirst.The prevalence of HUA in children and adolescents was higher than that in adults (χ²=4.193,P=0.041).The level of serum uric acid in the CDI patients with HUA and disappearance of thirst was higher than those without disappearance of thirst (U=2.593,P=0.010).The multiple linear regression predicted serum creatinine (β=0.472,95%CI=2.451-4.381,P<0.001) and body mass index (β=0.387,95%CI=6.18-12.874,P<0.001) as the independent risk factors of serum uric acid level increment in children and adolescents,while serum creatinine (β=0.361,95%CI=1.016-1.785,P<0.001),body mass index (β=0.208,95%CI=2.321-6.702,P<0.001),triglyceride (β=0.268,95%CI=12.936-28.840,P<0.001),and total cholesterol (β=0.129,95%CI=2.708-22.250,P=0.013) were the independent risk factors in adults. Conclusions The patients with CDI were more likely to have HUA,and the prevalence of HUA in children and adolescents was higher than that in adults.Body mass index,serum creatinine,triglyceride,total cholesterol,and disappearance of thirst were the risk factors for the increased level of serum uric acid in CDI patients.
Adolescent ; Adult ; Child ; Humans ; Uric Acid ; Creatinine ; Retrospective Studies ; Diabetes Insipidus ; Hyperuricemia ; Triglycerides ; Cholesterol ; Diabetes Mellitus

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ² test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27⁺⁴ weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.
Infant, Newborn ; Pregnancy ; Female ; Humans ; Infant ; Placenta Accreta/surgery* ; Pregnancy Trimester, Second ; Pregnant Women ; Cesarean Section ; Retrospective Studies ; Blood Loss, Surgical ; Placenta ; Abortion, Induced ; Hysterectomy

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c.1016delT (p.L339Rfs*5) and c.1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. CONCLUSION The child was diagnosed with 3-methylglutenedioic aciduria type VII. Discovery of the c.1016delT and c.1087A>G variants has enriched the mutational spectrum of the CLPB gene.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Base Sequence ; Metabolism, Inborn Errors/diagnosis* ; Mutation ; Neutropenia/genetics* ; Sequence Analysis, DNA

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.
Rats ; Animals ; Synoviocytes ; Matrix Metalloproteinase 2/metabolism* ; Network Pharmacology ; Receptor, Fibroblast Growth Factor, Type 1/therapeutic use* ; Arthritis, Rheumatoid/genetics* ; Signal Transduction ; Fibroblasts ; Drugs, Chinese Herbal/therapeutic use*

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
Contrast Media ; Diagnosis, Differential ; Epidermal Cyst ; Humans ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal/diagnostic imaging* ; Sensitivity and Specificity ; Testicular Neoplasms/diagnostic imaging* ; Ultrasonography/methods*

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.
Child ; Infant ; Female ; Pregnancy ; Humans ; Adiposity ; Diabetes, Gestational/epidemiology* ; Overweight/epidemiology* ; Thinness ; Cohort Studies ; Body Mass Index ; Obesity