Non-invasive imaging of pathological scars using a portable handheld two-photon microscope / 中华医学杂志(英文版)

BACKGROUND@#Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo . This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.@*METHODS@#Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.@*RESULTS@#Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t = 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001).@*CONCLUSIONS@#Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Application of the interleukin-23 inhibitor guselkumab in the treatment of psoriasis / 中华皮肤科杂志

Guselkumab is the first monoclonal antibody that selectively targets interleukin (IL) -23. Several randomized controlled clinical trials have demonstrated that it is highly effective and safe in the treatment of moderate to severe plaque psoriasis, and can significantly improve the quality of life of patients. This review summarizes the action mechanisms of IL-23 and guselkumab, as well as the application of guselkumab in the treatment of psoriasis.

Immunoprotective role of dendritic cells in Chlamydia muridarum respiratory infection / 中华微生物学和免疫学杂志

Objective:To investigate the role of dendritic cells (DC) in Chlamydia muridarum ( Cm) respiratory infection and their effect on adaptive immune response. Methods:C57BL/6 mice were exposed to 1×10 3 inclusion-forming units (IFU) of Cm through inhalation to establish the mouse model of Cm respiratory infection. The proportion of CD11c + MHCⅡ + DC and the expression of costimulatory molecules (CD40, CD80 and CD86) in spleen tissues were detected by flow cytometry on 0, 3 and 7 d after infection. The expression of IL-12p40, IL-10 and IL-6 at mRNA level in spleen tissues was detected by qPCR. Mouse splenic DC isolated on 7 d after Cm infection were sorted by magnetic beads and then transferred to recipient mice. Th1 response in the recipient mice was measured using intracellular cytokine staining 14 d after infection. Results:Cm respiratory infection induced massive infiltration of DC and promoted the expression of costimulatory molecules on splenic DC. The expression of IL-12 and IL-10 at mRNA level in splenic DC reached the peak on 3 d after infection. Transferring the splenic DC of Cm-infected mice into the recipient mice could alleviate the disease condition in the recipient mice after Cm infection with reduced Cm inclusion-forming units in lung tissues and significantly increased proportion of Th1 cells in lung and spleen tissues. Conclusions:Cm respiratory infection could induce the maturation and activation of DC, which promoted Th1 immune response. DC played an important role in Cm infection.

Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies / 中华医学杂志(英文版)

BACKGROUND@#Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.@*METHODS@#We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.@*RESULTS@#We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9.@*CONCLUSION@#This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.

A survey report on the application status of artificial intelligence in medical imaging in China / 中华放射学杂志

Objective:To explore the current status of the artificial intelligence (AI) developments in medical imaging in China, and to provide data for the development of AI.Methods:In May 2022, the Radiology Branch of the Chinese Medical Association and the China Medical Imaging AI Industry-University-Research Innovation Alliance jointly launched a nationwide survey on the application status and development needs of medical imaging AI in China in the form of a questionnaire. This survey was carried out for different groups of people, focusing on the clinical applications of medical imaging AI, enterprise development, and educational needs in colleges and universities, with the descriptive statistical analysis performed.Results:China′s medical imaging AI has made great progress in clinical applications, in enterprise developments, as well as in the education and teaching areas. In terms of clinical application, 90.8% (5 765/6 347) of the survey respondents had a preliminary understanding of AI. There were 62.1% (3 798/6 119) doctors confirmed the applications medical imaging AI products in their departments. AI products were applied in the whole process of medical imaging examination, especially in assistance of the diagnosis. The application of pulmonary nodules screening accounted for 89.5% (3 401/3 798) of all medical imaging AIs. The main factors restricting the rapid development of medical imaging AI included lack of experts [47.3% (3 002/6 347)], poor data quality [45.7% (2 898/6 347)] and imperfect function of the products [40.4% (2 566/6 347)]; in terms of enterprises, there were 65.4% enterprises with a scale of less than 100 employees (17/26), and 34.6% with a scale of more than 100 employees (9/26). The main group of the customers were the hospitals above the second level, accounting for about 92.3% (24/26); in terms of education, the number and quality of AI courses, practical operations and lectures currently carried out by schools vary between different levels. The AI courses for graduated students accounted for about 22.5% (86/381), which were the largest in number; while the proportion of AI courses for junior college students, undergraduates and regular trainees were less than 15%. More than 60% of the students thought it necessary for schools to establish AI courses. Among all the students, the master′s and doctoral candidates had the greatest demand for additional AI courses [84.8% (323/381)].Conclusions:The development and popularization of medical imaging AI in China continues to prosper, with opportunities and challenges coexisting. It is necessary to adhere to the orientation of clinical needs, and to realize the coordinated development of clinical application, enterprise development, as well as education and teaching.

Efficiency and safety of traditional growing rod technique in the treatment of early onset dystrophic scoliosis secondary to type 1 neurofibromatosis with intraspinal rib head in children / 中华骨科杂志

Objective:To investigate the efficiency and safety of traditional growing rod in the treatment of early onset dystrophic scoliosis secondary to type 1 neurofibromatosis (NF1-DS) with intraspinal rib head in children.Methods:From September 2006 to May 2020, this study recruited 20 children with intraspinal rib head with early onset NF1-DS who had received traditional growing rods. There were 13 boys and 7 girls and the age of the initial operation was 7.0±1.6 years (range, 4.1-9.8 years). There were 7 cases of simple left chest bend, 9 cases of simple right chest bend, and 4 cases of double chest bend; 13 patients had varying degrees of kyphosis deformity. Two children had neurological symptoms before surgery, American Spinal Injury Association Impairment Scale (AIS) were grade D. The proportion of the intraspinal rib head (IRP), the Cobb angle of the main chest bend, apical vertebra rotation (AVR), apical vertebral translation (AVT), trunk shift (TS) and sagittal TK, lumbar lordosis (LL), sagittal balance and T 1-S 1 height were measured before and after first time internal fixation and at last follow-up, and the complications were also evaluated. Results:All 20 patients were followed up and the average follow-up time was 41.6±23.8 months (range, 24-99 months). A total of 85 operations was conducted including 63 protrude operations. After operation, the IRP was significantly lower than that before operation (preoperative 33.1%±17.5% vs. postoperative 22.2%±11.3%, P<0.001) and no significant correction loss was found at last follow-up 23.7%±12.4% ( P>0.05). The mean Cobb angle decreased from 75.9°±26.7° preoperatively to 45.0°±18.5° postoperatively ( P<0.001) and there was still significant improvement at the last follow-up (41.0°±17.2°) compared with postoperatively ( P<0.05). The AVR was significantly reduced after surgery compared with preoperatively (33.0°±10.1° vs. 39.3°±13.3°, P<0.001), and the last follow-up (40.1°±11.4°) was significantly improved compared with postoperative ( P=0.005). The T 1-S 1 height increased from 259.8±70.7 mm preoperatively to 296.9±78.4 mm postoperatively ( P=0.001), and at the last follow-up 296.9±78.4 mm was still significantly higher than after operation ( P<0.001), with an average annual increase of 12.4±3.2 mm. Significant correction of AVT, TK, LL and sagittal balance were noted after initial surgery ( P<0.05), and no significant correction loss was found at last follow-up ( P>0.05). There were 10 complications in 7 cases. There were 5 complications of pedicle screw loosening, 1 complication of bolt droping, 2 complications of broken rod, 1 complication of distal junctional kyphosis and 1 complication of adding-on phenomenon. 2 cases with nerve injury were recover after operation (AIS grading E). None of the children had new neurological complications during growth rod insertion and multiple stretching during follow-up. Conclusion:For children with early onset NF1-DS with intraspinal rib head, if the preoperative AIS grade is D or E, traditional growing rod technique is relatively safe and effective and can make the intraspinal rib head remove from the spinal canal partly.

Characterization of chromatin accessibility in psoriasis / 医学前沿

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.

How phosphorylation of RBCs band 3 protein affects storage quality of suspended red blood cells prepared from Tibetan high Hb population / 中国输血杂志

【Objective】 To investigate the quality changes of suspended red blood cells (SRBCs) prepared from the blood of Tibetan high Hb population, and explore the availability and safety of blood collected from Tibetan high Hb population. 【Methods】 The voluntary blood donors were grouped according to the Hb concentration at the initial screening: female blood donors from Tibet Autonomous Region (>3 500 m) with Hb≥190 g/L and male blood donors with Hb≥210 g/L were classified as plateau high hemoglobin group. A total of 13 male blood donors from Tibet Autonomous Region were recruited. And the female blood donors (n=13) with Hb(115~165) g/L and male blood donors (n=12) with Hb(120~185) g/L from Chengdu were classified as control group. Whole blood of 200 mL specification was centrifuged to remove the plasma, and MAP additive solution was added to prepare SRBCs, then SRBCs were divided into four aliquots (50 mL/bag and stored at 4℃. Parameters as blood routine, free Hb and hemolysis rate were measured aseptically at day 1, 14, 21, 35 of storage. And 10 mL SRBCs was used to extract membrane proteins for tyrosine phosphorylation detection of band 3 protein. 【Results】 The RBCs counts(×1012/L), hematocrit(%) and hemoglobin(g/L) of Tibetan high Hb group and control group were 6.76±0.95 vs 4.65±0.52, 63.3±6.8 vs 43.1±4.4 and 214.4±19.8 vs 143.2±16.9 (P<0.01). The erythrocyte deformability test on the day 1, 14, 21, 35 of storage showed that the deformability of SRBCs prepared from Tibetan high Hb group was significantly lower than that of the control group under shear stress of 3, 5.33, 9.49, 16.87, and 30 Pa, while the hemolysis rate of SRBCs prepared from the Tibetan high Hb group and the control group on the day 1, 14, 21, 35 were 0.050 2±0.040 2 vs 0.022 2±0.011 1, 0.055 4±0.043 vs 0.032 1±0.028 7, 0.061 2±0.025 9 vs 0.034 3±0.031 7 and 0.069 6±0.032 0 vs 0.044 0±0.033 3 (P<0.05). Western blotting showed that the cytoplasmic N-terminal Y21 of band 3 protein of SRBCs prepared from Tibetan high Hb group was highly phosphorylated. 【Conclusion】 The deformability of SRBCs prepared from the Tibetan high Hb group was significantly lower while the hemolysis rate of SRBCs was higher than that of the control group. The hemolysis rate of the SRBCs at the end of storage prepared from the Tibetan high Hb group meets the requirements of the national standard GB18469-2012(<0.8%). The increase of hemolysis rate of SRBCs prepared from the Tibetan high Hb group was closely related to the phosphorylation of band 3 protein.

A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and LateOnset Psoriasis in China

Background@#Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP;＜40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C*06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. @*Objective@#To investigated HLA genetic heterogeneity between EOP and LOP in China. @*Methods@#We first calculated the MHC-based heritability of EOP and LOP respectively.Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previousstudy. @*Results@#We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%).Further association analysis identified three independent loci (HLA-C*01:02, p=6.70×10−8 ; HLA-A amino acid position 9, p=3.27×10−17 ; and HLA-A amino acid position 161, p=5.75×10−10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C*06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C*06:02-positive psoriasis patients have earlier onset. @*Conclusion@#Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

Clinical blood use in Tibet Autonomous Region People′s Hospital: A respective study of 2014~2018 / 中国输血杂志

【Objective】 To retrospectively investigate the clinical transfusion status in Tibet Autonomous Region People′s Hospital, in order to provide data basis for further improvement of the rational and scientific blood use in our hospital. 【Methods】 Medical records of transfusion recipients in our hospital from 2014 to 2018 were investigated via HIS system, and such indicators as total clinical blood use, usage of whole blood and blood components, blood transfusion per capita, usage of blood components with different types. and the usage of red blood cells and plasma in each clinical department were retrospectively analyzed. 【Results】 The total clinical blood usage of our hospital increased from 3 930.5 U in 2014 to 4 949 U in 2018, with an annual growth rate of 5.93%. The average blood use per capita in 2014 and 2018 was 0.205 U vs 0.218 U, and incidence of blood component transfusion was 47.18% vs 99.02% The proportion of blood component (red blood cell and plasma) usage was 36.0%, 35.9%, 20.7% and 7.4% for blood type O, A, B and AB, respectively. The usage of total blood, red blood cell and plasma in internal and surgical departments were 13 883.8 U vs 7 080.8 U, 4 963.3 U vs 3 647.3 U and 6 055 U vs 1 170 U, respectively. 【Conclusion】 The total clinical blood usage and the proportion of blood component transfusion in our hospital is increasing year by year. Therefore, rational and scientific blood use should be further improved.