[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[The applications and challenges of liquid chromatography tandem mass spectrometry in maternal and child health].

Due to its ultra-high sensitivity, specificity and throughput, liquid chromatography tandem mass spectrometry (LC-MS/MS) has become an important analytical tool in clinical laboratories in quantifying various small molecules, such as vitamins, bile acids, steroids and other internal metabolites relevant to maternal diseases. As an effective means of screening and diagnosing diseases in preventive medicine, LC-MS/MS has been widely used in maternal and child health, contributing to the reduction of the incidence of maternal and child diseases and premature morbidity and mortality. At present, LC-MS/MS is an emerging and powerful platform in laboratory testing in China, facing both challenges and opportunities. In this article, the representative applications in the field of maternal and child health are summarized and discussed, along with the major hurdles of LC-MS/MS in clinical recognition and implementation.

[Correlation study between brain damage and anxiety, depression, and cognitive impairment in patients with moderate to severe obstructive sleep apnea hypopnea syndrome using diffusional kurtosis imaging].

Objective: To explore the brain white matter damage in patients with moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) using diffusional kurtosis imaging(DKI), and to analyze its relationship with anxiety, depression and cognitive impairment in patients. Methods: This was a retrospective case-control study. Fifty confirmed cases (47 males and 3 females) of moderate to severe OSAHS diagnosed by polysomnography(PSG) from November 2017 to December 2022 were selected as OSAHS group(age range from 22 to 65 years old, with median age of 40 years old), and 32 healthy controls(27 males and 5 females) of non-OSAHS diagnosed by PSG were selected as control group(age range from 19 to 56 years old, with median age of 34 years old). DKI scanning, Beck Anxiety Inventory(BAI), Beck Depression Inventory-Ⅱ(BDI-Ⅱ), and Montreal cognitive assessment(MoCA) scores were performed in all subjects. Differences in kurtosis fractional anisotropy(KFA) of various brain regions were compared between the two groups to identify differential brain regions. Correlations were analyzed between KFA reduction and anxiety, depression, and cognitive impairment in OSAHS patients. To study the correlation between brain injury and anxiety, depressive mood, and cognitive dysfunction, statistical methods such as non-parametric tests for two independent samples, chi-square tests, and partial correlation analysis, were used to analyze the evaluation indicators of the two groups. Results: The KFA values in right external capsule, left anterior corona radiata, right anterior corona radiata, left posterior corona radiata, right posterior corona radiata, left superior corona radiata, right superior corona radiata, left superior longitudinal fasciculus, right superior longitudinal fasciculus, genu of corpus callosum, splenium of corpus callosum, body of corpus callosum, posterior cingulate gyrus of moderate to severe OSAHS group were all lower than those in the control group(t=-2.247, -3.028, -3.955, -4.871, -2.632, -2.594, -2.121, -2.167, -3.129, -2.015, -2.317, -2.313, -2.152,P<0.05). For the moderate to severe OSAHS group, the correlation between AHI and KFA values of right posterior corona radiata, right superior corona radiata, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.378, -0.307, -0.337, -0.343, -0.341, -0.613, -0.390, -0.384, -0.396, P<0.05). The correlation between LSO2 and KFA values of right anterior corona radiata, right posterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, posterior cingulate gyrus were all positive(r=0.330, 0.338, 0.425, 0.312, 0.433, 0.358, 0.410, 0.459, 0.473, 0.659, 0.489, 0.356, P<0.05). The correlation between BAI scores and KFA values of right external capsule, right anterior corona radiata, left posterior corona radiata, left superior corona radiata, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.306, -0.372, -0.296, -0.346, -0.318, -0.386, P<0.05). The correlation between BDI-Ⅱ scores and KFA values of right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.334, -0.289, -0.309, -0.310, -0.503, -0.469, P<0.05). The correlation between MoCA scores and KFA values of right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all positive(r=0.368, 0.431, 0.324, 0.410, 0.469, 0.384, 0.369, 0.309, P<0.05). Conclusions: With the aggravation of OSAHS, the damage to some brain regions becomes more pronounced in moderate to severe OSAHS patients. These damage brain functional areas are closely related to the anxiety, depression, and cognitive impairment of patients.

[Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature].

Objective: To report a case of the pulmonary surfactant protein(SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease(ILD), and review the related literature, to investigate the relationships of ABCA3 gene mutation associated with ILD in infants. Method: A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University. The clinical, radiological, histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed; 12 reports retrieved on literature search at Pubmed, OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed. Result: (1)The patient, a 6-months-old boy, had progressive tachypnea and dyspnea since 4 months old. Physical examination on admission revealed respiratory rate of 78 times/min , heart rate of 187 times/min, SpO2 0.93(mask oxygen-inspiration with 6 L/min), scattered fine moist crackles could be heard over the both lungs, clubbing fingers were found. High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity, interlobular and intralobular septal thickening. Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis. SP-A and SP-B were negative in immunohistochemical stainting. SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c. 1942A>G, c.2701-33G>C and c. 991-105C>A. (2)The review of related literature found that totally 12 cases were reported. The main manifestations were progressive tachypnea and dyspnea, age of onset was between birth and 4 years of age. The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung. PROGNOSIS: 6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.