This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective:To explore the association of different obesity measurement indexes on serum C-reactive protein (CRP) in Chinese adult women.Methods:The data were obtained from baseline and follow-up surveys of the urban Breast Cancer Screening Program in Shuangliu District, Chengdu. A total of 441 adult women were included in the study. A questionnaire survey, physical examination, and laboratory testing were conducted on the subjects. Multivariate logistic regression model, two-level mixed effects logistic regression model, and restricted cubic spline method were used to investigate the linear and nonlinear correlation between different obesity measurement indexes and serum CRP in adult women.Results:For every 1 unit increase in BMI, waist circumference (WC), and adiposity, the risk of elevated serum CRP or exacerbation of chronic low-grade inflammation in adult women increased by 16.5%, 5.0%, and 11.1% ( P<0.05), respectively. Both BMI and adiposity were nonlinear correlated with serum CRP. Using BMI=24.0 kg/m 2 as the reference point, serum CRP level increased with the increase of BMI when BMI >24.0 kg/m 2. Using adiposity=30% as the reference point, serum CRP level increased with the increase of adiposity when adiposity >30%. Conclusions:Overall, obesity reflected by BMI had the strongest association with serum CRP in adult women, followed by body fat content reflected by adiposity, and central obesity reflected by WC had the weakest association with CRP. Adult women with BMI >24.0 kg/m 2 or adiposity >30% are at high risk for obesity-related inflammatory manifestations.

Objective:To explore the risk factors of cement displacement after percutaneous vertebral augmentation in patients with osteoporotic vertebral compression fracture (OVCF).Methods:A case-control analysis was made on clinical data of 1 538 patients with OVCF admitted to Honghui Hospital Affiliated to Xi′an Jiaotong University from January 2016 to June 2021. There were 377 males and 1 161 females, aged from 45-115 years [(71.7±10.8)years]. Percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) was performed. Patients were divided into cement displacement group ( n=78) and cement non-displacement group ( n=1 460) according to the radiographic outcomes. Factors related to cement displacement were analyzed by univariate analysis, including age, gender, body mass index (BMI), preoperative bone mineral density, underlying diseases, involved vertebral segments, surgical methods, surgical approaches, cement leakage (anterior edge), viscosity of cement, dispersion ratio of cement, degree of cement interweaving, sagittal position of cement, targeted location of cement, distance from cement to upper and lower endplates and duration of brace wearing. Independent risk factors for bone cement displacement were identified by multivariate Logistic regression analysis. Results:Univariate analysis showed that bone cement displacement was significantly correlated with BMI, preoperative bone mineral density, involved vertebral segments, operation methods, cement leakage (anterior edge), viscosity of cement, dispersion ratio of cement, degree of cement interweaving, sagittal position of cement, targeted location of cement, distance from cement to upper and lower endplates and duration of brace wearing (all P<0.05), but there was no correlation with gender, age, underlying diseases or surgicales approach (all P>0.05). Multivariate Logistic analysis showed that the preoperative bone mineral density ( OR=2.45, 95% CI 1.81-7.50, P<0.01), operation methods ( OR=4.56, 95% CI 1.86-8.44, P<0.01), cement leakage (anterior edge) ( OR=5.77, 95% CI 2.85-9.20, P<0.01), viscosity of cement ( OR=7.36, 95% CI 1.01-1.77, P<0.01), dispersion ratio of cement ( OR=6.84, 95% CI 1.69-13.39, P<0.01), degree of cement interweaving ( OR=8.97, 95% CI 2.29- 14.97, P<0.01), sagittal position of cement ( OR=6.39, 95% CI 1.06-9.47, P<0.01), targeted location of cement ( OR=7.93, 95% CI 1.64-11.84, P<0.01), distance from cement to upper and lower endplates ( OR=6.78, 95% CI 1.84-6.96, P<0.01) and duration of brace wearing ( OR=9.55, 95% CI 2.26- 9.38, P<0.01) were significantly correlated with bone cement displacement after percutaneous vertebral augmentation. Conclusion:Low bone mineral density preoperatively, PKP, cement leakage into the vertebral anterior edge, low viscosity of cement, small dispersion ratio of cement, small degree of cement interweaving, cement filling in the anterior 1/3 and anterior middle 2/3 of the vertebral body in sagittal plane, non-targeted injection of cement, long distance from cement to upper and lower endplates and short duration of brace wearing are independent risk factors of cement displacement after percutaneous vertebral augmentation for OVCF.

Objective: To explore the menopausal symptoms and quality of life of hormone receptor positive (HR+ ) breast cancer patients at different endocrine therapy time. Methods: The HR+ breast cancer patients who were pathologically confirmed from 2011 to 2017 in the Sichuan Cancer Hospital were divided into three groups according to endocrine therapy time (<12 months, 12~36 months, >36 months) and analyzed by a cross-sectional study. The Menopausal symptoms and quality of life of these patients were measured using the modified Kupperman scale and the functional assessment of cancer therapy-breast cancer (FACT-B) scale. The differences of menopausal symptoms among different time groups and drug groups were analyzed by Chi-square test. The differences of quality of life and the effects of menopausal symptoms on quality of life were tested by covariance and multiple linear regression analyses. Results: The average score of menopausal symptom of 167 patients was 14.5±7.6 and the prevalence rate was 87.4% (146/167). Among all of the menopausal symptoms, the prevalence rate of insomnia was the highest (73.7%, 123/167). Besides insomnia and excitement, hot flashes was more prevalent in selective estrogen receptor modulator (SERM) users (64.8%, 79/122) , while osteoarthritis was more prevalent in aromatase inhibitor (AI) users (62.2%, 28/45). The total score of FACT-B of Patients was 104.5±15.5, and the compliance rate was up to 89.8% (150/167). However, the condition of each dimension was different, the compliance rates of social/ family and functional dimension were lowest, which were 73.0% (122/167) and 50.9% (85/167), respectively. The menopausal symptoms of patients at different time groups were 15.0±1.3, 14.0±6.9, 14.5±7.4, respectively, and the total score of FACT-B of patients at different time groups were 102.7±17.8, 105.0±12.9, 105.6±16.7, respectively, without significant differences (both P>0.05). Multiple linear regression analysis showed that menopausal symptoms impaired the quality of life of SERM users during the endocrine therapeutic period. The standardized regression coefficients of three time groups were -0.67, -0.30, -0.50, respectively, with the lowest effect on 12~36 months group. Conclusion HR+ breast cancer patients will have a poor function recovery and social/ family return, who need more attention. Menopausal symptoms are common problems during endocrine therapy, and active measures should be taken to improve patients′ quality of life.

The inverse problem of electrical impedance tomography (EIT) is seriously ill-posed, which restricts the clinical application of EIT. Regularization is an important numerical method to improve the stability of the EIT inverse problem as well as the resolution of the imaging. This paper proposes a self-diagnosis regularization method based on Tikhonov regularization and diagonal weight regularization method (DWRM). Firstly, the ill-posedness of the inverse problem is analyzed by sensitivity. Then, the performance of the self-diagnosis regularization is analyzed through the singular value theory. Finally, some simulated experiments including simulations and flume experiment are carried out and verify that the self-diagnosis regularization has better image quality and anti-noise ability than those of traditional regularization methods. The self-diagnosis regularization method weakens the ill-posedness of inverse problem of EIT and can prompt the practical application of EIT.

BACKGROUND: The therapy of nonunion has been a difficult issue in orthopedics all the time. Part of nonunion can't heal even after many times of operations. The effects of non-surgical treatments are not satisfactory. Extracorporeal shock waves (ESW) is a new method that popular abroad in recent years.OBJECTIVE: To investigate the effect of ESW on nonunion, and preliminarily probe into its mechanism.DESIGN: Randomized group-division design, animal experiment.SETTING: Department of Orthopedics, Renmin Hospital of Wuhan University.MATERIALS: The experiment was conducted in the Medical Experimental Center of Animal, Wuhan University from September 1997 to March 1999. Forty healthy male rabbits were selected to establish model of nonunion. Thirty-two rabbits with hypertrophic nonunion were taken as materials and randomly divided into treatment group and control group with 16 rabbits in each group.METHODS: A multifunctional ESW apparatus of type HX902Ⅲ was adopted to treat the broken ends of nonunion in the treatment group with the energy, frequency, dose and focus range of 0.54 m J/mm2, 60 times/minute,2 000 times and 1.5 cm2 respectively. The second focus of shock wave was adjusted, aiming at corresponding parts in distal and proximal sites of nonunion, and acted 1 000 times. After that, rabbits were re-fixed with external apparatus and acted freely. Rabbits in the control group were fixed with external apparatus without any other treatments.MAIN OUTCOME MEASURES: Examination of the healing of nonunion with radiograph, transmission electron microscope (TEM) and in histology.RESULTS: A total of 32 enrolled animals were involved in the analysis of results.①X-ray photograph: During the treatment with ESW, the gaps of nonunion were more and more indistinct in X-rays, and the densities of two sclerotic ends were reduced, and the sclerotic marrow cavities became unobstructed. The X-rays of nonunion-gaps before ESW were significantly narrowed than those after the treatment. At 6 weeks after the treatment,nonunion in 6 rabbits of the treatment group (6/14) healed, and that in 12 animals (12/12) healed on the 12th week. However, only the nonunion in one rabbit (1/12) healed in the control group on the 12th week. Test of fourfold-table exact probability demonstrated that the healing status of nonunion in the treatment group was better than the control group, and the differences were remarkable (P＜0.001).②Examination under light microscope: large quantity of osteoblasts and mesenchymal cells assembled and were active in proliferation on the 2nd week of treatment in the treatment group, and plentiful bone trabeculae formed on the 6th week, and the nonunion healed on the 12th week of treatment. However, there were chronic inflammation and few trabeculae in the control group. ③TEM examination: the osteoblasts in the treatment group proliferated on the 2nd week of treatment, and there were abundant chondrosomes in the intracytoplasm,which could secrete collagen fibers with periodical transverse lines. On the 6th week, large amount of bone lacunas formed. However, little visible cells could be seen in the control group, and osteoclasts were found in act.CONCLUSION: The effect of ESW on hypertrophic nonunion is satisfactory, which may become a reliable and non-invasive treatment of nonunion.