OBJECTIVE: To study the mechanisms of Tongxia Huayu Decoction (a Chinese herbal decoction for purgation and removing blood stasis) in prognostic improvement for severe acute pancreatitis by early intervention on pancreatic microcirculatory disturbance. METHODS: Fifty-three patients with severe acute pancreatitis were divided randomly into treatment group (n=28) and control group (n=25). Tongxia Huayu Decoction was given to the patients in treatment group in addition to the normal treatment in control group for one week. The clinical symptoms and signs, hemodiastase, urinary amylase, C-reactive protein (CRP) and endothelin (ET) of the patients in the two groups before and after treatment were observed and detected. RESULTS: The total response rate of the treatment group was 98.4%, while that of the control group was 80%, with significant difference between them (P<0.05). There was no significant difference of the contents of hemodiastase, urinary amylase, CRP and ET between the two groups before treatment, while they were significantly decreased after treatment (P<0.01) with more obvious change in treatment group (P<0.01). CONCLUSION: Tongxia Huayu Decoction brings satisfied therapeutic effect on severe acute pancreatitis. The mechanisms may associate with its reducing function on ET releasing so as to inhibit the pancreatic microcirculatory disturbance and acinar cell injury induced by ET.

Objective: To predict the prognosis of cervical cancer, we constructed a novel model with 5 specific cell types and identified a potential biomarker. Methods: We employed CIBERSORT and xCell method to evaluate the abundances of 23 cells types in tumor microenvironment. Five specific cell types were filtrated to determine different immunotypes by applying least absolute shrinkage and selection operator (LASSO) Cox regression method. The expression of immune checkpoints (ICPs) and effectors were validated by immunohistochemistry. Correlation analysis was performed to examine the relevance between PIK3CA mutational status and ICPs. Results: Unsupervised clustering of patients on the basis of tumor infiltrating lymphocytes and fibroblasts identified patients with shorter overall survival (OS) (hazard ratio [HR]=3.0729; 95% confidence interval [CI]=1.5103–6.2522; p=0.0118). An immunoscore (IS) signature consisting of 5 immune cell types infiltrating in tumor core (CD8T, activated NK cells, neutrophils, activated mast cells, macrophages) was constructed using LASSO Cox regression analysis. Receiver operating characteristic curves confirmed that the area under the curve of IS was significantly higher to that of International Federation of Gynecology and Obstetrics staging alone (0.637 vs. 0.55). Survival analysis revealed patients in high IS group exhibited a poorer OS (HR=3.0113; 95% CI=1.8746–4.8373; p<0.0001). The multivariate analysis indicated the IS was an independent prognostic factor. In addition, the lower IS related to higher expression of ICPs and neoantigen load. Conclusions The identification of IS in cervical cancer tissues could facilitate patient risk stratification and selection of immunotherapeutic responses, but more prospective studies are needed to assess its reliability.

Objective: To cross-cultural adapt the English version of obturator functioning scale (OFS) to form a simplified Chinese version, to preliminarily verify its reliability and validity in clinic, and to provide an effective tool for evaluating the oral function and quality of life of patients with palatal defect and restored with obturators in China. Methods: The English version of the OFS was taken for forward translation, synthesis, back-translation, and reviewed by expert committee to develop a pre-testing simplified Chinese version. This scale contained demographic data, basic information of diseases, eating problems dimensions (3 items), speech problems dimensions (5 items), and other problems dimensions (7 items). From December, 2016 to December, 2018, forty-two patients who were treated in the Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University with palatal defect and restored with obturators were evaluated with OFS. Among them, there were 26 males, and 21-84 years old, and 16 females, who were 24-80 years old.The reliability and validity of the data were examined and analyzed. Results: The results showed that Cronbach′s α coefficients of the overall scale and the three dimensions (eating problems, speech problems, and other problems) were 0.926, 0.938, 0.930, and 0.935, respectively. The internal consistency of the questionnaire was very good. The Spearman coefficients between each single dimension and the total score were 0.677, 0.792, and 0.860, respectively, suggesting that the scale convergence was good. The content validity index of 15 items was 0.905, indicating that the content validity was very good. Conclusions The Chinese version of the OFS is exhibiting high reliability and validity, providing an effective evaluation tool of oral function and quality of life for Chinese patients with obturator prostheses to restore palate defects.

Objective:Using ultrasound imaging technology to evaluate the contraction characteristics of diaphragm in patients with chronic low back pain.Methods:Twenty nine patients with chronic low back pain and 26 healthy persons recruited from the rehabilitation department of the Third Affiliated Hospital of Sun Yat-sen University from November 2019 to April 2020 were selected and divided into the low back pain (LBP) group and the healthy control group. The thickness of the diaphragm (Tdi) of the subjects during deep breathing was evaluated by portable color Doppler ultrasound equipment under different body positions. The subjects were required to perform maximum inspiration for total lung capacity (TLC) and expiration for functional residual capacity (FRC) in the supine and standing position, respectively. The end-inspiratory diaphragm thickness (TdiTLC) and end-expiratory diaphragm thickness (TdiFRC) were recorded, and the diaphragmatic thickening fraction (DTF) was calculated. The general data of subjects with lower back pain and the correlation between Oswestry Dysfunction Index (ODI) and diaphragm function were analyzed; The diaphragm function of healthy control group and LBP group were compared; The receiver operating characteristic (ROC) curve of Tdi and DTF in the diagnosis of lower back pain were analyzed.Results:ODI lifting score was negatively correlated with standing TdiTLC ( r=-0.50, P<0.01). In intra-group comparison, the TdiTLC and TdiFRC values of healthy subjects in standing position were increased compared with those in supine position ( t=6.115, 7.314, all P<0.001); In standing position, TdiTCL and TdiFRC values in LBP group were increased compared with those in supine position ( t=2.834, 4.673, all P<0.01). In comparison between groups, TdiTLC values in supine and standing position of LBP group were significantly lower than those in healthy control group ( t=2.597, 3.338, all P<0.05); In standing position, TdiFRC of patients in LBP group was significantly lower than that of healthy control group ( t=2.098, P=0.041) and DTF value of patients in LBP group was significantly lower than that of healthy control group ( t=2.902, P=0.006). When TdiTCL≤3.3 mm in supine position was used to predict low back pain, the diagnostic sensitivity and specificity were 78.6% and 53.8%, respectively, and the area under the curve was 0.661. When TdiTCL≤4.5 mm in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 95.7% and 46.2%, respectively, and the area under the curve was 0.759. When DTF≤81.3% in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 52.2% and 84.6%, respectively, and the area under the curve was 0.698. Conclusions:It is found in our study that the diaphragm contractile function of patients with lower back pain is worse than that of normal subjects, and the difference was significant in standing position. We suggest that the right-side ultrasound image acquisition in the patient′s standing position is helpful to ensure the accuracy and objectivity of the measurement results. TdiTCL≤4.5 mm or DTF≤81.3% in standing position can be used as one of the reference indexes for the combined diagnosis of chronic low back pain.

Objective To analyze the effect of ultrasound-guided glucocorticoid injection on different pathologies of the shoulder retrospectively.Methods Clinical data were collected describing 75 patients with shoulder pain who received ultrasound-guided glucocorticoid injection and finished 3 month follow-ups in the rehabilitation clinic of the Third Affiliated Hospital of Sun Yat-sen University between April and September of 2017.The patients were divided into three groups based on their different injection sites:group 1 was injected at the subacromial bursa alone,group 2 was injected at both the subacromial bursa and the coracoid bursa,while group 3 was injected at the subacromial bursa and the long head of the tendon sheath of the biceps brachii.A shoulder pain and disability index (SPADI) was used to quantify the pain and disability of each patient before and after the injection.Results Significant improvement was observed in the average pain and disability scores of all groups at 1 week,1 month and 3 months after the injection.Moreover,significant and continuous improvement was observed in the average pain and disability scores of groups 1 and 3,as well as the average disability score of group 2 from right after the injection until the last follow-up.However,no significant differences were found in the average pain score between one and three months after the injection.There was no significant difference among the 3 groups in the average pain and disability scores before and immediately after the injection.Conclusion Ultrasound-guided glucocorticoid injection is effective and persistent for treating shoulder pain with different pathologies.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Objective:To explore the application effect of integrated mode of medical and nursing in colostomy patients.Methods:Using the convenient sampling method, a total of 60 patients who underwent colostomy in the Second Affiliated Hospital of Wenzhou Medical University from January 2019 to April 2020 were selected as the research objects. The patients who hospitalized from January to August 2019 were included in the control group, and the patients who hospitalized from September 2019 to April 2020 were included in the observation group, with 30 cases in each group. The patients in the control group were treated with routine nursing mode, and the patients in the observation group were treated with integrated mode of medical and nursing. Before discharge, 1, 3 and 6 months after the operation, the status of independent replacement of colostomy bags, scores of the Stoma Self-care Scale-Early Version and the incidence of stoma complications were compared between the two groups.Results:There was no statistically significant difference in the number of patients who changed colostomy bags independently before discharge and 1, 3 and 6 months after the operation between the two group ( P>0.05) . There was no statistically significant difference in the number of cases of periostomy dermatitis, ostomy and mucosal separation and stoma depression between the two groups of patients after surgery ( P>0.05) . The score of the Stoma Self-care Scale-Early Version of the observation group were higher than that of the control group at 3 and 6 months after surgery, and the difference was statistically significant ( P<0.05) . Conclusions:The integrated mode of medical and nursing can improve the self-care ability of patients at 3 and 6 months after the operation , which is worthy of clinical application.

BACKGROUNDThe initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated.

METHODSA porous ACP/PLLA composite and PLLA scaffold (as a control) were incubated in fetal bovine serum (FBS) containing phosphate-buffered saline (PBS), and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy (SEM). The expression levels of the genes encoding integrin subunits α1, α5, αv, β1, focal adhesion kinase (FAK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits α1, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite.

CONCLUSIONSThe ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits α1, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.

Biocompatible Materials ; chemistry ; Calcium Phosphates ; chemistry ; Cell Adhesion ; physiology ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Humans ; Integrin alpha1 ; metabolism ; Integrin alpha5 ; metabolism ; Integrin alphaV ; metabolism ; Integrin beta1 ; metabolism ; Integrins ; genetics ; metabolism ; Lactic Acid ; chemistry ; Osteoblasts ; cytology ; Porosity ; Tissue Engineering ; methods

Objective To characterize the species of common sandflies in Henan Province using DNA barcoding with cytochrome c oxidase subunit I (COI) gene as the molecular marker, and to analyze the genetic polymorphisms of sandflies, so as to provide insights into visceral leishmaniasis prevention and control in Henan Province. Methods Sandfly specimens were sampled from 13 sandflies surveillance sites from 2021 to 2023 in Anyang City, Zhengzhou, Luoyang and Xuchang cities (Zhengzhou-Luoyang-Xuchang areas) where visceral leishmaniasis cases were reported and in Jiaozuo and Xinxiang cities (Jiaozuo-Xinxiang areas) without visceral leishmaniasis cases reported. Genomic DNA was extracted from a single sandfly, and COI gene was amplified. The amplification product was subjected to bidirectional sequencing. Following sequence assembly, the species of sandflies was characterized through sequence alignment using the BLAST tool. The intra-specific and inter-specific genetic distances of sandflies were estimated among different areas using the software Mega 11, and phylogenetic trees were created. The polymorphisms of nucleotide sequences in the sandflies COI gene were estimated using the software DnaSP. The fixation index (F_ST) of different geographical isolates of sandflies was calculated using the Arlequin software, and the gene flow value (Nm) was used to measure the gene flow in the sandflies populations. In addition, the population genetic structure of different geographical populations of Phlebotomus chinensis was analyzed using the STRUCTURE software. Results A total of 978 sandflies were collected from 13 sandflies surveillance sites in Zhengzhou-Luoyang-Xuchang areas, Jiaozuo-Xinxiang areas and Anyang City of Henan Province from 2021 to 2023, and 475 sandflies were randomly sampled for subsequent detections. A total of 304 Ph. chinensis, 162 Se. squamirostris and 9 Se. bailyi were identified based on molecular biological detection of the COI gene, and Se. bailyi was reported for the first time in Henan Province. The intraspecific genetic distances of sandflies were 0.000 to 0.040, and the inter-specific genetic distances ranged from 0.133 to 0.161. Phylogenetic analysis revealed that each of the three sandfly species was clustered into a clade. The genetic polymorphisms of Ph. chinensis populations varied among different areas, with the highest haplotype diversity (0.966 ± 0.007) and the greatest nucleotide diversity (0.011) in Zhengzhou-Luoyang-Xuchang areas, and the lowest haplotype diversity (0.720 ± 0.091) and nucleotide diversity (0.004) in Anyang City. The dominant haplotype of Ph. chinensis populations was Pch_Hap_2 in Anyang City and Jiaozuo-Xinxiang areas, with moderate genetic differentiation (0.05 < F_ST < 0.15) and frequent gene exchange (Nm value > 1) between Ph. chinensis populations sampled from Anyang City, and Jiaozuo-Xinxiang areas. Population genetic structure analysis showed that the dominant component of Ph. chinensis populations was K5 in Anyang City and Jiaozuo-Xinxiang areas. No obvious dominant haplotype was observed in Ph. chinensis populations sampled from Zhengzhou-Luoyang-Xuchang areas, which had very high genetic differentiation (F_ST > 0.25) and little gene exchange (Nm value < 1) with Ph. chinensis populations from Anyang City, and Jiaozuo-Xinxiang areas, with K3 as the dominant component. In addition, there was no significant difference in the genetic polymorphism level among Se. squamirostris populations from the three areas. Conclusions There are Ph. chinensis, Se. squamirostris and Se. bailyi in Henan Province, and S. bailyi is recorded for the first time in Henan Province by molecular biological assays. There are different levels of genetic differentiation and gene exchange among P. chinensis populations in different areas of Henan Province.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.