Objective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:To retrospectively analyze the effects of vitamin D supplementation on the clinical efficacy of ustekinumab (UST) in treatment of patients with Crohn′s disease (CD).Methods:Seventy-one patients with moderate to severe active CD who received the first-line treatment UST from May 2021 to February 2023 were collected by searching the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. The disease activity of CD was evaluated by Harvey-Bradshaw index (HBI) and intestinal inflammation was assessed by simplified endoscopic score for Crohn′s disease (SES-CD). The CD patients were divided into supplementary group ( n=41) and non-supplementary group ( n=30) based on whether vitamin D supplementation (400 U/d) was performed during UST treatment. According to the baseline serum 25 (OH) D level, the patients were divided into vitamin D deficiency group (<20 μg/L, n=42) and non-deficiency group (≥20 μg/L, n=29). The main end points were the differences in the clinical remission (HBI score ≤4) rate and mucosal healing (SES-CD score ≤2) rate between supplementary group and non-supplementary group at week 24 of UST treatment. The secondary end points were the differences in the clinical response (the reduction of HBI score ≥3 compared to week 0) rate and biochemical remission (C-reactive protein (CRP)≤5 mg/L) rate between supplementary group and non-supplementary group at week 8 of UST treatment. A multiple linear regression analysis was performed to investigate the relation between serum 25(OH) D levels and the clinicopathological characteristics of CD patients. Multivariate binary logistic regression models were used to analyze the factors affecting the clinical efficacy of UST at week 8 and 24. Independent sample t test, Mann-Whitney U test, Chi-square test and Fisher′s exact test were used for comparisons between the two groups. Paired t test was used to analyze the differences before and after UST treatment. Results:The results of multiple linear regression analysis for 71 CD patients showed that the baseline serum 25(OH)D level was independent influencing factor for the baseline CRP level ( β=-0.33, 95% confidence interval (95% CI) -0.41 to -0.08, P=0.041) and baseline HBI score ( β= -0.52, 95% CI -0.68 to -0.33, P=0.027). Compared with week 0, the serum 25(OH)D level of supplementary group increased at week 8 ((17.18±5.46) μg/L vs. (13.71±7.73) μg/L), and the difference was statistically significant ( t=-7.81, P<0.001), however, there was no significant difference of serum 25(OH)D in non-supplementary group ((14.85±3.92) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 8, the HBI score and median CRP level of supplementary group were both lower than those of non-supplementary group (5.71±1.88 vs. 8.34±2.27, 10.83 mg/L (3.95 mg/L, 21.07 mg/L) vs. 16.17 mg/L (6.91 mg/L, 35.48 mg/L)), and the diffierences were statistically significant ( t=0.48, Z=2.87; P<0.001 and =0.001). However, the clinical response rate and biochemical remission rate were both higher than those of non-supplementary group (68.3%, 28/41 vs. 40.00%, 12/30 and 43.9%, 18/41 vs. 13.3%, 4/30), and the differences were statistically significant ( χ2=5.64 and 6.21, P=0.018 and 0.013). Compared with week 0, the serum 25(OH)D level of supplementary group increased ((24.73±8.34) μg/L) at week 24, and the difference was statistically significant ( t=-6.83, P<0.001), however, there was no statistically significant difference in the serum 25(OH)D level of non-supplementary group ((15.59±7.24) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 24, the decrease of HBI score and SES-CD score of supplementary group were both greater than those of non-supplementary group (difference between week 24 and week 0 -8.96±1.45 vs. -5.33±0.59, -7.00(-10.00, -3.00) vs. -2.00(-2.50, -1.50), and the differences were statisticalcy significant ( t=-5.64 and Z=-3.27, P<0.001 and =0.039). Moreover, the clinical remission rate and mucosal healing rate were both higher than those of non-supplementary group (65.9%, 27/41 vs. 26.7%, 8/30, and 61.0%, 25/41 vs. 30.0%, 9/30), and the differences were statistically significant ( χ2=10.64 and 6.66, P=0.001 and 0.010). At week 24, the analysis of non-supplementary group indicated that the clinical remission rate and mucosal healing rate of patients received vitamin D supplementary therapy were both higher than those of patients without vitamin D supplementary therapy (69.0%, 20/29 vs. 3/13, and 58.6%, 17/29 vs. 2/13), and the differences were statistically significant ( χ2=4.43 and 5.14, P=0.035 and 0.023). Vitamin D supplementing therapy was an independent influencing factor of clinical response rate and biochemical remission rate at week 8, clinical remission rate and mucosal healing rate at week 24 for UST treatment of CD ( OR(95% CI) were 5.83(1.15 to 7.59), 4.91(3.67 to 6.98), 5.13(2.88 to 9.44), 7.01(1.16 to 20.97), respectively; P<0.001, <0.001, <0.001, =0.036). Conclusion:Vitamin D supplementation may help to improve the clinical efficacy of UST treatment in CD patients, especially in patients with vitamin D deficiency.

Objective:To explore the relationship between gene polymorphisms of integral protein alpha-4 ( ITGA4) and intercellular adhesion molecule-1 ( ICAM-1) and the risk of ulcerative colitis (UC), and to analyze the effects of ITGA4 and ICAM-1 gene variations on the clinical response of vedolizumab (VDZ) treatment in UC patients at week-14. Methods:From January 1, 2010 to January 31, 2023, at Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University, a total of 500 UC patients (UC group) and 529 gender- and age-matched healthy controls (healthy control group) were collected. The 500 UC patients were divided into mildly active stage (264 cases) and moderately to severely active stage (236 cases); distal colitis (299 cases), extensive colitis (201 cases); of the 500 UC patients, 120 cases received VDZ treatment, and 78 cases achieved clinical response and the remaining 42 cases had no response at week-14. Chi-square test and unconditional logistic regressionmodel were used to analyze the difference in gene polymorphisms of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene polymorphisms between UC group and healthy control group, between patients of mildly active stage and patients of moderately to severely active stage, between patients with distal colitis and patients with extensive colitis, between patients with clinical response and patients without response through dominant, recessive, and allelic gene models. Results:The results of dominant gene model analysis showed that, the frequency of the variant allele G and the variant genotype AG+ GG of ITGA4 rs6740847 of UC group were lower than those of healthy control group (28.60% vs. 33.18%, 48.00%vs. 56.15%), the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 of UC group were higher than those of healthy control group (37.30% vs.31.57%, 62.20% vs. 54.63%), and the differences were statistically significant( χ2=5.04, 6.83, 7.49 and 6.06, P=0.025, 0.009, 0.006 and 0.014); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with moderate to severe active UC were lower than those of patients with mild active UC (25.42% vs. 31.44%, 43.22% vs. 52.27%), while the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 were both higher than those of mild active UC (40.89% vs. 34.09%, 66.95% vs. 57.96%), and the differences were statistically significant( χ2=4.42, 4.09, 4.93 and 4.29, P=0.036, 0.043, 0.026 and 0.038); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847, the variant allele T of ITGA4 rs7562325, and the variant allele G and variant genotype AG+ GG of ICAM-1 rs5498 of patients with extensive colitis UC were lower than those of patients with distal colitis UC (24.38% vs. 31.44%, 39.80% vs. 53.51%, 33.58% vs.39.80%, 19.65% vs.26.09%, 35.82% vs. 45.82%), and the differences were statistically significant( χ2=5.87, 9.05, 3.97, 5.54 and 4.94, P=0.015, 0.003, 0.046, 0.019 and 0.026); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with clinical response were higher than those of patients without response (34.62% vs.21.43%, 61.54% vs. 33.33%), and the differences were statistically significant( χ2=4.52 and 8.70, P=0.039 and 0.001). The results of recessive gene model analysis showed that, the frequency of variant genotype TT of ITGA4 rs7562325 of UC group was higher than that of healthy control group (12.40% vs.8.51%), and the difference was statistically significant ( χ2=4.18, P=0.041); the frequency of variant allele G and variant genotype GG of ICAM-1 rs5498 of patients with moderate to severe active UC were higher than those of patients with mild active UC (27.33% vs. 20.08%, 8.47% vs. 2.27%), and the differences were statistically significant( χ2=7.30 and 9.72, P=0.007 and 0.002); the frequency of variant allele T and variant genotype TT of ITGA4 rs7562325 of patients with clinical response were lower than those of patients without response (32.05% vs. 45.24%, 10.26% vs. 23.81%), and the differences were statistically significant( χ2=4.09 and 3.93, P=0.043 and 0.047). Conclusions:The variation of ITGA4 rs6740847 gene may reduce the risk and disease activity of UC, and may increase the clinical response to VDZ treatment in UC patients. However, the variation of ITGA4 rs7562325 gene may increase the risk and disease activity of UC, and may reduce the clinical response to VDZ treatment in UC patients. The variation of ICAM-1 rs5498 gene may worsen the disease activity of UC. In addition, the variations of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene may all reduce the risk of extensive colitis.

Objective To analyze the immunological effect and its influencing factors of HAART on HIV/AIDS with a baseline CD4 of less than 350 cells/mm³ in Hubei Province during 2011-2020. Methods The treatment information of people living with HIV/AIDS (PLWH) was collected through China Disease Control and Prevention Information System, and the change of CD4 mean value was analyzed by Wilcoxon sign rank sum test. Chi square test and multivariate logistic regression were used to analyze the factors influencing the immunological effect. Results The mean value of CD4 cell count at baseline was (172.78±107.65) cells/mm3 before treatment and (398.85±206.71) cells/mm³ in the fifth year after treatment. Patients with baseline CD4<50 /mm3 had the largest increase in CD4 mean value after treatment (P<0.05). Multivariate logistic regression analysis showed that Age ≥35 years, heterosexual transmission, time interval from diagnosis to treatment≥1 month, baseline CD4<50 /mm3, treatment time 7-<18 months, and drug failure were the risk factors for the success of antiviral therapy(P<0.05). Conclusion The immunological effect of HIV/AIDS antiviral therapy in Hubei Province is affected by many factors. It is necessary to strengthen the implementation of early detection and early treatment strategy and promote treatment compliance education for patients aged ≥35 years.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective:To retrospectively analyze the effects of vitamin D3 supplementation on clinical remission of patients with Crohn′s disease (CD) in the treatment of infliximab (IFX).Methods:From January 2014 to January 2020, 73 patients with initial moderate to severe CD (50 patients with vitamin D deficiency (the level of serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/L)) receiving IFX treatment at Department of Gastroenterology were screened from the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. Harvey-Bradshaw index (HBI) was applied to evaluate the disease activity of CD patients. All the patients underwent IFX treatment (5 mg/kg) for at least 54 weeks. According to whether vitamin D3 (125 U/d) was supplemented during IFX treatment, the patients were divided into supplemented group ( n=37) and non-supplemented group ( n=36). In supplemented group, the level of 25(OH) D of patients at the 54th week was compared with that before IFX treatment. At the 54th week, the clinical remission rate and decline range of HBI were compared between supplemented group and non-supplemented group. And the influencing factors of clinical remission rate were analyzed in CD patients. Paired t test, independent sample t test, chi-square test and multivariable logistic regression were used for statistical analysis. Results:In supplemented group, the level of serum 25(OH)D at the 54th week was higher than that before IFX treatment ((50.83±15.45) nmol/L vs. (37.68±16.75) nmol/L), and the difference was statistically significant ( t=-4.55, P<0.001). At the 54th week, the clinical remission rate of supplemented group was higher than that of non-supplemented group (83.8%, 31/37 vs. 61.1%, 22/36), the decline range of HBI was larger than that of non-supplemented group (7.41±3.00 vs. 6.28±2.75), and the differences were statistically significant ( χ2=4.71, t=2.41; P=0.030 and 0.023). The results of multivariable logistic regression analysis showed that vitamin D3 supplementation was an independent factor affecting the clinical remission rate in CD patients ( n=73) and the patients with vitamin D deficiency ( n=50) ( b= -1.67 and -1.92 , P=0.015 and 0.019). Conclusions:Vitamin D3 supplementation can significantly improve the clinical remission rate in CD patients with IFX treatment, especially in CD patients with vitamin D deficiency.

OBJECTIVE: To analyze the clinical features and genetic variants in four neonates with very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. METHODS: Neonates with a tetradecenoylcarnitine (C14:1) concentration at above 0.4 μmol/L in newborn screening were recalled for re-testing. Four neonates were diagnosed with VLCAD deficiency by MS-MS and genetic testing, and their clinical features and genotypes were analyzed. RESULTS: All cases had elevated blood C14:1, and the values of first recalls were all lower than the initial test. In 2 cases, the C14:1 had dropped to the normal range. 1 case has remained at above 1 μmol/L after the reduction, and the remainder one case was slightly decreased. In total eight variants of the ADACVL genes were detected among the four neonates, which included 5 missense variants and 3 novel variants (p.Met344Val, p.Ala416Val, c.1077+6T>A). No neonate showed salient clinical manifestations. CONCLUSION Above findings have enriched the spectrum of ADACVL gene mutations and provided a valuable reference for the screening and diagnosis of VLCAD deficiency.
Acyl-CoA Dehydrogenase/genetics* ; Acyl-CoA Dehydrogenase, Long-Chain ; Congenital Bone Marrow Failure Syndromes ; Genetic Testing ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; Mitochondrial Diseases ; Muscular Diseases ; Tandem Mass Spectrometry

Objective:To investigate the relationship between polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 ( CDKN2 B- AS1) gene and the risk of ulcerative colitis (UC). Methods:From January 2012 to January 2021, a total of 534 UC patients diagnosed at the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University (Yuying Children′s Hospital) and during the same period 560 gender- and age-matched healthy controls were selected. Genotypes of CDKN2 B- AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) in venous blood were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression was used to analyze the difference in the distribution of CDKN2 B- AS1 gene polymorphisms between UC patients and healthy controls, as well as the influence on the clinicopathologic characteristics of UC patients. Software Haploview 4.2 was used to analyze the linkage disequilibrium and haplotype. Chi-square test was used for statistical analysis. Results:The frequencies of variant genotype (AG+ GG) and variant allele (G) of rs1063192 in UC patients were higher than those in healthy controls (32.4%, 173/534 vs. 24.8%, 139/560; 18.1%, 193/1 068 vs. 13.7%, 153/1 120), and the differences were statistically significant ( OR=1.45 and 1.40, 95% confidence interval(95% CI) 1.12 to 1.89 and 1.11 to 1.77, P=0.006 and 0.004, corrected P=0.030 and 0.020). The frequency of variant allele (G) of rs10757274 in UC patients was lower than that in healthy controls (34.7%, 371/1 068 vs. 39.5%, 442/1 120), and the difference was statistically significant ( OR=0.82, 95% CI 0.69 to 0.98, P=0.025). However, the difference was not significant after Bonferroni correction (corrected P>0.05). According to the Montreal classification, the frequency of homozygous variant genotype (GG) of rs1063192 in the patients with extensive colitis was higher than that in patients with proctitis plus left-sided colitis (6.6%, 14/211 vs. 1.9%, 6/323), and the difference was statistically significant ( OR=3.92, 95% CI 1.47 to 10.42, P=0.006, corrected P=0.030). There was linkage disequilibrium among rs10757274, rs2383207, rs10757278 and rs1333048 of CDKN2 B- AS1 gene. The frequency of haplotype GGGC in UC patients was lower than that in healthy controls (33.3%, 355.5/1 068 vs. 37.8%, 423.4/1 120), and the frequency of haplotype AGGC in UC patients was higher than that in healthy controls (6.7%, 71.7/1 068 vs. 3.6%, 40.3/1 120), and the differences were statistically significant ( χ2=4.81 and 11.16, P=0.028 and<0.001). Conclusions:The variation of rs1063192 in CDKN2 B- AS1 gene may increase the risk of UC. The risk of extensive colitis in patients carrying homozygous variant genotype (GG) of rs1063192 may rise. Among the haplotypes composed of rs10757274, rs2383207, rs10757278 and rs1333048, the risk of UC may decrease in the individuals carrying haplotype GGGC. However, the risk of UC may increase in the individuals carrying haplotype AGGC. The correlation between the variation of 10757274 and the risk of UC still needs to be further verified by expanding the sample size.