Abstract Backgroud Homocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure. Objective To investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance. Methods Immunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages. Results Hcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = −3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = −2.19, p = 0.030). Study limitations The small serum sample size in the study. Conclusion The high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging. Hcit, , (Hcit) diseases However (CBL obscure aging significance SK, (SK) distant 05 0 5 0. lesion, lesion lesion) group ages cells 0806 806 0.806 0.0002. 00002 0.0002 . 0002 0.0002) Z 3703 3 703 −3.703 05763 5763 0.5763 0.0032 00032 0032 0682 682 0.682 0004 004 0.004 respectively. respectively respectively) 219 2 19 −2.19 0.030. 0030 0.030 030 0.030) study (Hcit (SK 080 80 0.80 0000 0.000 000 370 70 −3.70 0576 576 0.576 0.003 0003 003 068 68 0.68 00 0.00 21 1 −2.1 0.03 03 08 8 0.8 37 7 −3.7 057 57 0.57 06 6 0.6 0.0 −2. −3. −2 −3 −

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22–2.31; HR: 2.28, 95% CI 1.50–3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20–4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06–0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA. 201 COVID19 COVID 19 (COVID-19 , (RA) (PsA . (SpA) multicentre multi centre January 202 2022. 2022 2022) postvaccine physiciandefined physician dose (HR 95 CI. (CI) 237 1563 (156 41 39 SpA) 213 21 21.3% 241 24 1 24.1 218 8 21.8 respectively 102 10 2 10.2% 110 11 0 11.0 149 14 9 14.9 moderatehigh moderate high 168 68 1.68 1.22–2.31 122231 22 31 228 28 2.28 150348 50 48 1.50–3.48 respectively) 221 2.21 1.20–4.08. 120408 1.20–4.08 20 4 08 1.20–4.08) 008 0.08 0.06–0.10. 006010 0.06–0.10 06 0.06–0.10) onefifth one fifth COVID-1 nonsevere. nonsevere non severe. non-severe COVID1 (COVID-1 (RA (SpA (CI 23 156 (15 21.3 24. 21. 10.2 11. 14. 16 6 1.6 1.22–2.3 12223 2.2 15034 5 1.50–3.4 12040 1.20–4.0 00 0.0 00601 0.06–0.1 COVID- (COVID- 15 (1 10. 1. 1.22–2. 1222 2. 1503 1.50–3. 1204 1.20–4. 0. 0060 0.06–0. (COVID ( 1.22–2 122 150 1.50–3 120 1.20–4 006 0.06–0 1.22– 12 1.50– 1.20– 0.06– 1.22 1.50 1.20 0.06 1.2 1.5

ABSTRACT BACKGROUND: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination. OBJECTIVE: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis. DESIGN AND SETTING: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China). METHODS: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease. RESULTS: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy. CONCLUSION: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Abstract Introduction: The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms. Methods: H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo. Results: After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function. Conclusion: Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.

RESUMO Introdução: O acidente vascular cerebral iatrogênico é um evento clínico que, em pouco tempo, leva à disfunção cerebral localizada ou difusa, fazendo com que o paciente desenvolva disfunções motoras. Objetivo: Estudar o efeito de atividade física baseada em evidências sobre a função física de pacientes de AVC com hemiplegia sobre sua capacidade de executar suas atividades da vida diária. Método: 160 pacientes com AVC iatrogênico foram selecionados e separados aleatoriamente em grupos. O grupo Exercício recebeu treino reabilitativo, além de terapia medicamentosa convencional básica, enquanto o grupo Controle recebeu apenas terapia medicamentosa. Em seguida, os efeitos da reabilitação foram avaliados. Resultados: A performance do grupo Exercício foi melhor que a do grupo Controle. A diferença entre os dois grupos foi estatisticamente significativa. Conclusão: Atividade física sistemática e baseada em evidências e métodos de reabilitação eficientes podem aliviar a disfunção motora de pacientes de AVC com hemiplegia. Nível de evidência II; Estudos terapêuticos – investigação do resultado de tratamentos.

ABSTRACT Introduction: Iatrogenic stroke is a cerebrovascular clinical event. It quickly leads to localized or diffuse brain dysfunction. After the onset, the patient develops motor dysfunction. Objective: To study the effect of evidence-based physical exercise on the physical function and daily life ability of stroke patients with hemiplegia. Results: The performance of the exercise group was better than that of the control group. The difference between the two groups was statistically significant. Conclusion: Systematic evidence-based exercise and effective rehabilitation methods can alleviate the motor dysfunction of stroke patients with hemiplegia. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: El accidente vascular cerebral iatrogénico es un evento clínico que, en poco tiempo, ocasiona disfunción cerebral localizada o difusa, haciendo que el paciente desarrolle disfunciones motoras. Objetivo: Estudiar el efecto de actividad física basada en evidencias sobre la función física de pacientes de ACV con hemiplejia sobre su capacidad de ejecutar sus actividades de vida diaria. Método: Fueron seleccionados y separados aleatoriamente en grupos 160 pacientes con ACV iatrogénico. El grupo Ejercicio recibió entrenamiento de rehabilitación, además de terapia medicamentosa convencional básica, mientras que el grupo Control recibió solo terapia medicamentosa. A continuación, los efectos de la rehabilitación fueron evaluados. Resultados: El rendimiento del grupo Ejercicio fue mejor que la del grupo Control. La diferencia entre los dos grupos fue estadísticamente significativa. Conclusión: Actividad física sistemática y basada en evidencias y métodos de rehabilitación eficientes pueden aliviar la disfunción motora de pacientes de ACV con hemiplejia. Nivel de evidencia II; Estudios terapéuticos – investigación del resultado de tratamientos.

RESUMO Introdução: A função cardiovascular é um dos principais fatores que afetam a saúde. A influência da atividade física com diferentes intensidades na função cardiovascular precisa ser pesquisada mais a fundo. Objetivo: Estudar a relação entre atividade física e enfermidades cardiovasculares em idosos. Método: Este artigo realizou um questionário de acompanhamento com 1.564 idosos. Os idosos que praticam atividades físicas e aqueles que não o fazem passaram por testes de índices hemodinâmicos, que analisaram quais foram os efeitos relevantes da atividade física sobre sua função cardiovascular. Resultados: Idosos que praticam atividades físicas regularmente demonstraram boa adaptabilidade à atividade física. Conclusão: A atividade física pode ser benéfica para o funcionamento do sistema cardiovascular. Nível de evidência II; Estudos terapêuticos – investigação do resultado de tratamentos.

ABSTRACT Introduction: Cardiovascular function is one of the main factors affecting health. The influence of different exercise intensities on cardiovascular function needs further research. Objective: To study the relationship between physical activity and cardiovascular disease in the elderly. Method: The article conducted a follow-up survey of 1,564 older adults. Elders who practice sports and those who do not went through the hemodynamic index test, which analyzed the relevant effects of physical exercise on their cardiovascular function. Results: Older adults who exercise regularly show good adaptability to exercise. Conclusion: Physical exercise can promote the function of the cardiovascular system. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: La función cardiovascular es uno de los principales factores que afectan a la salud. La influencia de la actividad física con diferentes intensidades en la función cardiovascular necesita ser investigada más a fondo. Objetivo: Estudiar la relación entre actividad física y enfermedades cardiovasculares en ancianos. Método: Este artículo realizó un cuestionario de acompañamiento con 1.564 ancianos. Los ancianos que practicaban actividades físicas y aquellos que no lo hacen pasaron por pruebas de índices hemodinámicos, que analizaron cuáles fueron los efectos relevantes de la actividad física sobre su función cardiovascular. Resultados: Ancianos que practican actividades físicas regularmente demostraron buena adaptabilidad a la actividad física. Conclusión: La actividad física puede ser benéfica para el funcionamiento del sistema cardiovascular. Nivel de evidencia II; Estudios terapéuticos – investigación del resultado de tratamientos.

Abstract Background: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance. Methods: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders. Results: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted β of 0.01 (95% confidence interval [CI]: -0.08–0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76–50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes. Conclusions: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.

RESUMO Objetivo: Este estudo explorou a aplicação clínica do desenho pré-operatório preciso para impressão 3D e reconstrução do polegar, para ajudar no controle e melhorar função e aparência. Métodos: Estudo retrospectivo de 20 pacientes submetidos à cirurgia de colheita de transplante de dedo do pé e reconstrução do polegar entre janeiro de 2015 e dezembro de 2016. O modelo 3D do defeito do polegar foi confeccionado e impresso. As dimensões da pele e dos ossos da área doadora foram precisamente projetadas como referência para a operação cirúrgica, realizada de acordo com o modelo. Resultados: O reparo perfeito foi alcançado com aparência e função satisfatórias. Todos os polegares reconstruídos sobreviveram (taxa de sobrevivência de 100%). O acompanhamento foi de 3-9 meses. A dorsiflexão máxima foi de 8-30° e a flexão máxima foi de 38-58°. A discriminação sensorial de dois pontos foi de 9-11 mm. No total, 17 pacientes reportaram índice “Excelente” e três índice “Bom” cada para a função reconstruída do polegar e da mão, respectivamente. O índice de satisfação foi de 85%. Conclusão: O design digital pré-operatório e a impressão 3D de acordo com os locais doador e receptor permitiram uma operação customizada. A operação foi mais precisa, com bom aspecto. Nível de Evidência II, Estudo Retrospectivo.

ABSTRACT Objective: This study aimed to explore the clinical application of preoperative precise design for 3D printing and thumb reconstruction, which could help manage the patients with thumb defect and achieve better function and appearance. Methods: This was a retrospective study of 20 patients who underwent the surgery of harvesting toe transplant and thumb reconstruction between January 2015 and December 2016. The 3D model of the thumb defect was created and printed. The dimensions of skin and bones from donor site were precisely designed as reference for surgical operation. The surgery was performed according to the model. Results: Perfect repair of defects was achieved with satisfying appearance and function. The reconstructed thumbs all survived (survival rate of 100%). Follow-up was 3-9 months. The maximum dorsiflexion was 8-30° and the maximum flexion was 38-58°. The two-point sensory discrimination was 9-11 mm. In total, 17 patients reposted “Excellent” satisfaction and three “Good”, each for the reconstructed thumb and hand function, respectively. The satisfaction rate was 85%. Conclusion: Preoperative digital design and 3D printing according to the donor and recipient sites allowed a tailored operation. The operation was more precise, the appearance of the reconstructed thumb was good. Level of Evidence II, Retrospective Study.

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110–6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066–4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180–3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182–3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562–0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.

Abstract Streptococcus pneumoniae is one of the most frequent opportunistic pathogens worldwide. DNA processing protein A (DprA) is an important factor involved in bacterial uptake and DNA integration into bacterial genome, but its role in S. pneumoniae virulence remains unclear. The aim of this study was to characterize the effects of the pneumococcal dprA gene on the pathogenesis of S. pneumoniae. To construct a dprA-deficient pneumococcal strain, the dprA gene of the S. pneumoniae strain D39 was inactivated. The virulence of this dprA-deficient strain, designated ΔD39, was compared with that of the wild-type strain by evaluating their respective capabilities to adhere to human pulmonary epithelial cells (PEC-A549) and by analyzing their choline-binding protein expression levels. In addition, the expression profiles of genes associated with virulence and host survival assays were also conducted with the mutant and the wild-type strain. Our results indicate that the capability of ΔD39 to adhere to the PEC-A549 airway cells was significantly lower (p < 0.01) compared with D39. Additionally, the 100-KD choline-binding protein was not detected in ΔD39. The addition of competence-stimulating peptide (CSP) lead to a significantly reduction of psaA mRNA expression in the dprA-deficient mutant and an increased level of psaA transcripts in the wild-type strain (p < 0.01). The median survival time of mice intraperitoneally infected with ΔD39 was significantly higher (p < 0.01) than that of mice infected with D39. The results of this study suggest that DprA has a significant effect on virulence characteristics of S. pneumoniae by influencing the expression of choline-binding protein and PsaA.

ABSTRACTPurpose:RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs), also known as small activating RNAs (saRNAs). Myogenic regulatory factor MyoD is regarded as the master activator of myogenic differentiation cascade by binding to enhancer of muscle specific genes. Stress urinary incontinence (SUI) is a condition primarily resulted from urethral sphincter deficiency. It is thus expected that by promoting differentiation of adipose-derived stem cells (ADSCs) into myoblasts by activating MyoD gene through RNAa may offer benefits to SUI.Materials and Methods:Rats ADSCs were isolated, proliferated in vitro, and identified by flow cytometry. Purified ADSCs were then transfected with a MyoD saRNA or control transfected. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to detect MyoD mRNA and protein expression, respectively. Immunocytochemical staining was applied to determine the expression of desmin protein in transfected cells. Cell viability was measured by using CellTiter 96® AQueous One Solution Cell Proliferation Assay kit.Results:Transfection of a MyoD saRNA (dsMyoD) into ADSCs significantly induced the expression of MyoD at both the mRNA and protein levels, and inhibited cell proliferation. Desmin protein expression was detected in dsMyoD treated ADSCs 2 weeks later.Conclusion:Our findings show that RNAa mediated overexpression of MyoD can promote transdifferentiation of ADSCs into myoblasts and may help treat stress urinary incontinence (SUI)–a condition primarily resulted from urethral sphincter deficiency.