[A multicenter study on respiratory pathogen detection with Mycoplasma pneumoniae pneumonia in children].

Objective: To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods: A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15th and December 20th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results: A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ²=10.62,P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×109 vs. 4.06 (2.91, 5.65)×109/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions: The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

[Analysis of clinical characteristics and related genetic variation of juvenile myasthenia gravis].

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients.

[Application of multidisciplinary treatment comprehensive management model for early-stage lung cancer].

Objective: To explore the application of multidisciplinary treatment (MDT) and comprehensive management model in the diagnosis and treatment of early-stage lung cancer, and analyze its clinical value and the feasibility and significance of promotion. Methods: A retrospective study of 470 patients in Xijing Hospital who underwent surgery after MDT from January 8, 2018 to December 31, 2019. There were 172 males and 298 females, aged from 23 to 79 (54.46±11.08) years. Basic diagnosis and treatment information as well as postoperative pathology were analyzed, of which 441 cases were recommended for surgery by MDT and 29 cases were subjectively requested for surgery. The patients' general condition, preoperative diagnosis and pathological results were compared, and the specific content of the MDT and comprehensive management model were summarized. We also explored the value of MDT integrated management model in early stage lung cancer treatment in the context of the current lung cancer incidence in China. Results: Among 470 surgical patients, the majority of males had solid nodules (69/172,40.1%), and the majority of females had ground glass nodules (135/298,45.3%). The distribution of nodules showed a trend of more upper lobe(277/470)than lower lobe(161/470) and more right lung(276/470) than left lung(194/470). Among the 441 patients recommended for surgery, 98.11% of males (156/159) and 97.87% of females (276/282) showed malignant pathology after surgery. Adenocarcinoma was the main pathological type (93.59% of males, 146/156; 97.46% of females, 269/276). Among the malignant pathological results, carcinoma in situ (42.31% of males, 66/156; 47.10% of females, 130/276) and stage I lung cancer (50.64% of males, 79/156; 47.46% of females, 131/276) were the most common. In all patients, 1.89% of the males (3/159) and 2.13% of the females (6/282) recommended for surgery showed benign postoperative pathology, of which tuberculosis and fungal infection were the main pathological types (66.67% for each gender, males 2/3, females, 4/6). The postoperative pathology of 29 patients who subjectively requested surgery was also tuberculosis and fungal infection as the main pathological types (69.23% of males, 9/13; 68.75% of females, 11/16). The MDT comprehensive management model made full use of a variety of auxiliary diagnostic technologies and combined the experience advantages of multidisciplinary participation to make up for the limitations of single-diagnosis. The overall diagnosis coincidence rate reached 98.09%, with strong consistency (Kappa>0.81). The positive predictive value (PPV) was 97.96%, the negative predictive value (NPV) was 100%, and the average patient diagnosis and treatment cycle was 24.28-26.51 days. Conclusions: The MDT comprehensive management model meets the consensus requirements. It has great advantages in diagnostic efficiency and diagnosis and treatment cycle, and has a high promotion and application value for the diagnosis and treatment of early-stage lung cancer. At the same time, tuberculosis and fungal infection should be regarded as an important differential diagnosis item.

[Summary of clinical research progression of apatinib combined with docetaxel in second-line treatment of advanced gastric cancer].

Objective: To investigate the progression-free survival (PFS) and safety of apatinib combined with docetaxel treated patients with advanced gastric cancer after failure of first-line chemotherapy. Methods: From March 2017 to May 2018, 23 patients with advanced gastric cancer who had received a failure of first-line chemotherapy (either fedocetaxel or paclitaxel) were treated with apatinib combined with docetaxel. The short-term efficacy and safety of the patients were observed. Results: The therapeutic effects of 20 patients were evaluated. Among them, 4 cases were partial response (PR), 13 patients were stable disease (SD), 3 patients were progressive disease (PD). The objective remission rate (ORR) was 20.0%, the disease control rate (DCR) was 85.0%, the median PFS (mPFS) was 4.5 months. The main adverse reactions were hypertension, vomiting and weakness. Conclusion: Apatinib combined with docetaxel applied in the second-line treatment of gastric cancer is safe and effective.

Clinical impact of serum miR-661 in diagnosis and prognosis of non-small cell lung cancer.

OBJECTIVE: The aim of this study was to evaluate whether serum miR-661 could serve as a biomarker for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:   The expression of serum miR-661 was detected in 150 cases of NSCLC and 114 cases of normal healthy controls by Real-time PCR. Receiver-operating characteristic (ROC) curve analysis was applied to analyze diagnostic value of serum miR-661. The relationship between serum miR-661 expression and clinicopathological characteristics was investigated. Overall survival was analyzed using Kaplan-Meier method. Moreover, Cox proportional-hazards regression analyses were performed to determine the prognostic value of serum miR-661 in NSCLC patients. RESULTS: We found that the expression of serum miR-661 was significantly upregulated in NSCLC compared with healthy controls (p < 0.01). The expression level of serum miR-661 was positively correlated with histological grade (p = 0.011), lymph node metastasis (p = 0.003), distant metastasis (p = 0.021) and clinical stage (p = 0.005). Then, ROC curve analysis showed that serum miR-661 has considerable diagnostic accuracy, with an area under the ROC curve (AUC) of 0.726 (p = 0.001). Moreover, NSCLC patients with serum miR-661 higher expression have shown significantly poorer overall survival than those with lower serum miR-661 expression (p = 0.004). Furthermore, multivariate analyses showed that serum miR-661 expression levels were an independent prognostic factor for survival in NSCLC patients. CONCLUSIONS: Overall, these findings indicate that serum miR-661 may be a potential biomarker for the diagnosis and prognosis of NSCLC.

Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells.

OBJECTIVE: We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. MATERIALS AND METHODS: We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. RESULTS: Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. CONCLUSIONS: STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

Hepcidin and iron metabolism associated with cardiometabolic risk factors in children: A case-control study.

BACKGROUND AND AIMS: Iron metabolism plays a crucial role in the development of cardiometabolic disease; however, the association between cardiometabolic risk factors (CMRFs) and hepcidin as well as other iron parameters remains unclear in children. The aims of this study were to compare the circulating hepcidin levels and iron metabolism between children with and without CMRFs and to investigate the association between those iron parameters and CMRFs. METHODS AND RESULTS: A case-control study was conducted among 1126 children aged 7-14 years in the case group (n = 563) with CMRFs and the healthy control group (n = 563). Iron parameters, lipids, and anthropometric characteristics were evaluated. The information on demographics, diet, and physical activities was either children reported or parent reported. Compared with the healthy controls, children with CMRFs had higher levels of hepcidin and lower levels of serum iron, transferrin, and soluble transferrin receptor (sTfR; P < 0.001). Besides, the odds ratios (ORs) for low levels of high-density lipoprotein (HDL) were 2.03, 0.21, and 0.33 in children with higher hepcidin, transferrin, and sTfR levels (P < 0.05). Furthermore, ORs for cardiometabolic risk were 0.50 (95% confidence interval (CI): 0.30-0.85, P < 0.05), 0.22 (95% CI: 0.12, 0.42, P < 0.01) and 0.19 (95% CI: 0.10, 0.36, P < 0.01) in children with higher serum iron, transferrin, and sTfR levels, respectively. CONCLUSION: The levels of hepcidin were higher, while those of iron, transferrin, and sTfR were lower in children with CMRF. Hepcidin was positively associated with the risk of low HDL levels, whereas transferrin and sTfR levels negatively correlated with the risk of low HDL levels. In addition, serum iron, transferrin, and sTfR levels were negatively associated with cardiometabolic risk.

Thrombin Activates Latent TGFß1 via Integrin αvß1 in Gingival Fibroblasts.

Transforming growth factor ß (TGFß) regulates cell proliferation, differentiation, migration, apoptosis, and extracellular matrix production. It also plays a pivotal role in the pathogenesis of gingival overgrowth. Thrombin is a key player in tissue repair, remodeling, and fibrosis after an injury, and it exerts profibrotic effects by activating protease-activated receptors. Connective tissue growth factor (CTGF or CCN2) modulates cell adhesion, migration, proliferation, matrix production, and wound healing. It is overexpressed in many fibrotic disorders, including gingival overgrowth, and it is positively associated with the degree of fibrosis in gingival overgrowth. In human gingival fibroblasts, we previously found that TGFß1 induced CCN2 protein synthesis through c-jun N-terminal kinase and Smad3 activation. Thrombin stimulates CCN2 synthesis through protease-activated receptor 1 and c-jun N-terminal kinase signaling. Curcumin inhibited TGFß1- and thrombin-induced CCN2 synthesis. In this study, we demonstrated that thrombin and protease-activated receptor 1 agonist SFLLRN induced latent TGFß1 activation and Smad3 phosphorylation in human gingival fibroblasts. Pretreatment with a TGFß-neutralizing antibody, TGFß type I receptor inhibitor SB431542, and Smad3 inhibitor SIS3 inhibited approximately 86%, 94%, and 100% of thrombin-induced CCN2 synthesis, respectively. Furthermore, blocking integrin subunits αv and ß1 with antibodies effectively inhibited SFLLRN-induced Smad3 phosphorylation and CCN2 synthesis and increased activated TGFß1 levels; however, similar effects were not observed for integrins αvß3 and αvß5. These results suggest that protease-activated receptor 1-induced CCN2 synthesis in human gingival fibroblasts is mediated through integrin αvß1-induced latent TGFß1 activation and subsequent TGFß1 signaling. Moreover, curcumin dose dependently decreased thrombin-induced activated TGFß1 levels. Curcumin-inhibited thrombin-induced CCN2 synthesis in human gingival fibroblasts is caused by the suppression of latent TGFß1 activation.