[Annual review of interventional pulmonology in 2022].

Interventional pulmonology is an essential part of the treatment of respiratory diseases and an important component of modern respiratory medicine. In recent years, interventional respiratory medicine has kept up with the trend of the times, constantly developing and integrating various techniques, expanding the scope of application of interventional respiratory medicine, and developing in the direction of personalized and precision medicine as well. Here, we reviewed the new progress and up-to-date research achievements of interventional pulmonology from December 2021 to September 2022.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Intervention effect of Potentilla discolor-Euonymus alatus on intestinal flora of type 2 diabetes mellitus rats.

OBJECTIVE: With this study, we aimed at exploring the regulation mechanism of Potentilla discolor-Euonymus alatus on intestinal flora of T2DM (Type 2 Diabetes Mellitus) rats induced by high-fat diet combined with streptozotocin. MATERIALS AND METHODS: T2DM rats were induced by high-fat diet combined with streptozotocin. There were normal control group, model group, metformin group, high-dose Chinese medicine group and low-dose Chinese medicine group. Each group included 10 rats. Normal control group: normal feeding, no modeling, ordinary feed, and gavage of 0.9% normal saline. Model group: T2DM rats, high-fat diet, and gavage of 0.9% normal saline. Metformin group: T2DM rats, high-fat diet and fed with metformin solution. High-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose of 6 times the clinical dose. Low-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose twice the clinical dose. The general situation of T2DM rats was observed, and the changes of intestinal flora were observed with 16SrDNA sequencing. RESULTS: The T2DM rats induced by high-fat diet combined with streptozotocin were molded. After intervention, at the class level, the ratio of γ-proteobacteria was 22.30% in the model group, 11.97% in the metformin group, 3.24% in the high-dose Chinese herbs group and 1.72% in the low-dose Chinese herbs group; the ratio of Erysipelothrix insidiosa was 4.73% in the model group, 4.68% in the metformin group, 3.93% in the high-dose Chinese herbsgroup and 2.92% in the low dose group; the ratio of Lactinobacillus was 2.30% in the model group, 0.01% in the metformin group, 0.00% in the high-dose Chinese herbs group, and 0.00% low-dose Chinese herbs group; at the portal level, the Firmicutes/Bacteroides was 0.88 in the normal control group, 3.40 in the model group, 1.71 in the metformin group, 2.74 in high-dose Chinese medicine group, and 1.34 in low-dose Chinese medicine group; at the genus level, the relative abundance of Lactobacillus in the model group was 3.28%, that of Akkermansia was 1.99%, that of Shigella coli was 22.08%, and that of Vibrio phaseus was 7.67%. All of them were improved after the intervention of metformin and traditional Chinese medicine. CONCLUSIONS: Potentilla discolor-Euonymus Alatus could improve the composition and structure of intestinal flora in T2DM rats and regulate the diversity of intestinal flora. The ratio of Firmicutes/Bacteroidetes was adjusted, mainly to increase the number of Bacteroides; the flora related to intestinal barrier was adjusted, mainly to increase the number of Lactobacillus and Akkermansia bacteria.

MiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway.

The article "MiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway, by S.-W. Wang, L.-X. Deng, H.-Y. Chen, Z.-Q. Su, S.-L. Ye, W.-Y. Xu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 498-505-DOI: 10.26355/eurrev_201801_14201-PMID: 29424909" has been withdrawn from the authors due to inaccuracies (there are some errors and incorrect data). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14201.

[A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza].

Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38℃) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2∶2∶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.

[The efficacy and safety of transbronchial lung cryobiopsy in interstitial lung disease: a prospective study].

Objective: To evaluate the efficacy and safety of transbronchial lung cryobiopsy (TBCB) and conventional transbronchial lung biopsy (TBLB) in the diagnosis of interstitial lung diseases(ILD). Methods: A prospective, self-control study was conducted during January 2017 and April 2017 in First Affiliated Hospital of Guangzhou Medical University. A total of 25 patients [male 16, female 9; mean age (51±13) years, range 24 to 70 years] with inconclusive diagnosis of interstitial lung diseases were sequentially enrolled. In the study, TBCB (TBCB group) and TBLB (TBLB group) were performed successively under general anesthesia in all patients. The size of biopsy specimens, the duration of procedures, complications and pathological results were recorded. Gaussian distribution data were compared between 2 groups by using Student's t test, while abnormal distribution data were compared by using Wilcoxon rank sum test. The incidences of bleeding and pathologic diagnostic yield between the 2 groups were compared by using Pearson chi-square test. A P-value< 0.05 was assumed to be statistically significant. Results: The specimen sizes of TBCB group and TBLB group were (12.3+ 4.9) and (3.1+ 1.9) mm(2) respectively (t=-18.268, P=0.000). The duration of procedures was (7.8±3.2) and (5.4±2.1)min respectively (Z=-3.001, P=0.003). In TBCB group, the diagnostic yield was 72% (18/25), with valuable pathological results in 2 cases (8%), but in 5 cases (20%) it failed to provide valuable pathological results. In TBLB group, the diagnostic yield was 12% (3/25). There were no useful pathological results in other 22 cases. The difference in the rate of useful pathological results between TBCB group and TBLB group was significant (χ(2)=20.779, P=0.000). There was no pneumothorax or severe bleeding. The rate of mild to moderate bleeding in TBCB group and TBLB group was 47.2%(50/106) and 18.9%(20/106) (χ(2)=19.195, P=0.000) respectively. Conclusion: TBCB is superior to TBLB for lung biopsy as indicated by larger sample size, higher diagnostic yield and less complication. TBCB is valuable for the diagnosis of ILD.

MiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway.

OBJECTIVE: The apoptosis of vascular endothelial cells (VEC) is related to ischemic stroke. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can upregulate Bcl-2 expression, reduce reactive oxygen species (ROS) production, and induce apoptosis. The level of miR-124 was significantly increased after cerebral ischemia. This study aimed to investigate the role of miR-124 in regulating PI3K expression, brain VEC apoptosis, and ROS production. MATERIALS AND METHODS: The expressions of miR-124, PI3K, p-AKT, and Bcl-2 in brain VEC of rats from the sham group and middle cerebral artery occlusion (MCAO) group were tested. Bioinformatics analysis showed the complementary binding site between miR-124 and PI3K mRNA. ROS content and cell apoptosis were detected by flow cytometry. Rat brain VEC were cultured in vitro and treated by oxygen-glucose deprivation (OGD) for 6 h. VECs were divided into four groups, including miR-NC, miR-124 inhibitor, pIRES2-blank, and pIRES2-PI3K groups, and were further treated by OGD. RESULTS: MiR-124 expression, ROS content, and cell apoptosis were markedly increased, whereas the levels of PI3K, p-AKT, and Bcl-2 were markedly reduced in rat VECs from MCAO group compared with that in the sham group. OGD treatment significantly induced VECs apoptosis, upregulated miR-124 expression and ROS content, and down-regulated the levels of PI3K, p-AKT, and Bcl-2. MiR-124 inhibitor or transfection of pIRES2-PI3K plasmid apparently enhanced PI3K, p-AKT, and Bcl-2 expressions, alleviated cell apoptosis and decreased ROS content in VECs induced by OGD. CONCLUSIONS: Our data demonstrated that miR-124 induced the apoptosis of brain vascular endothelial cells via the down-regulation of PI3K/AKT signaling pathway and promotion of ROS production.

[Measurement and analysis of tracheal inner diameter in Chinese adults using multi-slice spiral CT, multi-planar reconstruction and special window technique].

Objective: To measure the inner diameter of tracheal(TD) in Chinese adults by multi-slice spiral CT(MSCT), multi-planar reconstruction(MPR) with special window technique and analyze its influencing factors. Methods: A total of 824 normal adults(male 435, female 389) and 16 patients with small peripheral pulmonary nodules(SPN) receiving chest multi-slice spiral CT (MSCT) in the physical examination at the First Affiliated Hospital of Guangzhou Medical University between January, 2014 and December, 2015 were included and their records were retrospectively analyzed. The 16 patients with SPN received bronchoscopy and the images were recorded followed by measurement of tracheal diameter using software. MSCT and MPR images were obtained by the 3Dview software, and the inner diameter of the trachea at 4 horizontal positions were measured by special window technique (window width 500 Hu, window level 100 Hu): thoracic entrance (TD(1)), aortic arch (TD(2)), 2 cm higher than the carina of trachea (TD(3)) and the narrowest trachea (TD(4)). Results: The results of bronchoscopy and software measurement in 16 patients were consistent with those of MSCT and MPR combined with special window technique (P>0.05). The TD at 4 positions in adult males were larger than those of adult females (P<0.01). The TD values at each position for males and females were as follows: (18.9±1.7) and (15.6±1.3) mm (t=30.9, P<0.01) for TD(1), (18.8±1.6) and (16.1±1.2) mm (t=28.0, P<0.01) for TD(2), (19.0±1.6) and (16.3±1.3) mm (t=26.5, P<0.01) for TD(3), (18.4±1.5) and (15.5±1.1) mm (t=31.3, P<0.01) for TD(4), respectively. The age, weight and BMI were not significantly correlated with the tracheal diameter (P>0.05). The height was linearly correlated with the tracheal diameter: for males, TD(1)=0.071× height (cm) + 6.964 (r=0.249, P<0.05), TD(2)=0.064 × height (cm) + 7.898 (r=0.246, P<0.05), TD(3)=0.074 × height (cm) + 6.533 (r=0.279, P<0.05), TD(4)=0.056 × height(cm) + 8.811(r=0.226, P<0.05); while for females, TD(1)= 0.046× height (cm) + 8.331 (r=0.183, P<0.05), TD(2) = 0.058 × height (cm)+ 6.950(r=0.248, P<0.05), TD(3)=0.059 × height (cm)+ 7.052 (r=0.235, P<0.05), TD(4) =0.044× height (cm) + 8.520 (r=0.208, P<0.05). Conclusion: MSCT and MPR combined with special window technique are accurate and feasible for the measurement of adult tracheal diameter. The diameter of the trachea in males is larger than that in females, and it is positively correlated with height, but not with age, body weight and BMI. The tracheal diameter can be evaluated by linear regression equation.

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

OBJECTIVE: To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. METHODS: A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. RESULTS: The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. CONCLUSION: The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

Development and validation of an improved Bradford method for determination of insulin from chitosan nanoparticulate systems.

CONTEXT: Blank chitosan nanoparticles are currently used as reference for the calibration curve, which fails to resolve the supernatant of the nanoparticles in the interference of Coomassie Brilliant Blue G-250 reagent; supernatants are generated at different chitosan nanoparticulate prescriptions, which have different interferences. There are notable errors in the experimental results, and the method is not feasible. OBJECTIVE: In this study, an improved, rapid, and economic Bradford method was developed and validated. MATERIALS AND METHODS: The pH of the supernatant of blank chitosan nanoparticles was adjusted to 7-9 through adding saturated NaOH. The precipitation (free chitosan) in the solution was separated by centrifuging for about 10 min (4000 r/min). RESULTS: The method eliminated the interference of free chitosan of different prescriptions. The results showed that the method presented a linearity in the range of 50-300 microg/mL (R(2) = 0.9992), and possessed a good inter-day and intra-day precision based on relative standard deviation values (less than 3.10%). Recovery of the supernatant of blank chitosan nanoparticles was between 98.30 and 99.93%, and the recovery of blank chitosan nanoparticles was between 95.57 and 100.27%. DISCUSSION AND CONCLUSION: The method was further tested for determination of the association efficiency of insulin to nanoparticulate carriers composed of chitosan. Encapsulant release under simulated gastrointestinal fluids was evaluated.