[A case of pleural metastasis of malignant peripheral nerve sheath tumor].

Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.

[Factors affecting long-term survival of advanced high-grade serous ovarian cancer].

Objective: To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC). Methods: In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis. Results: There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group (P<0.01). The surgical complexity score (SCS), the preoperative serum CA125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity (OR=0.016, 95%CI: 0.004-0.063, P<0.01), ascites volume >500 ml (OR=3.193, 95%CI: 1.285-7.930, P=0.012), and SCS ≥8 (OR=17.433, 95%CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival (P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml (OR=5.199, 95%CI: 2.015-13.409, P=0.001), DS >2 (OR=15.264, 95%CI: 5.843-39.874, P<0.01) and SCS ≥4 (OR=4.176, 95%CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion: The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.

[Effect of occupational stress on the mental health of railway workers].

Objective: To explore the impact of occupational stress and shift work on the mental health of railway workers and provide a scientific basis for occupational health protection. Methods: In April 2019, stratified cluster sampling method was used to select 613 railway workers from Fuzhou railway as subjects. Job Content Questionnaire (JCQ) , Symptom Checklist-90 (SCL-90) , Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to investigate railway workers' occupational stress and mental health conditions. The influencing factors of railway workers' mental health were analyzed. Results: The detection rates of mental health problems, anxiety and depression of railway workers were 40.5% (248/613) , 4.4% (27/613) and 9.0% (55/613) , respectively. There were 250 railway workers with occupational stress (40.78%) . There were statistically significant differences in the total scores of SCL-90 among different groups of working age and education background (P<0.05) . And there were statistically significant differences in the SAS total scores among different groups of education background (P<0.05) . The detection rates of mental health problems and anxiety in the night shift group were higher than that in the white shift group, and the differences were statistically significant (P<0.05) . The detection rate of mental health problems in the group with occupational stress was higher than that in the group without occupational stress, and the difference was statistically significant (P<0.05) . Logistic regression analysis found that night shift work was the main risk factor affecting railway workers' anxiety (OR=2.38, 95%CI: 1.04-5.46, P<0.05) . The results of interaction analysis showed that compared with the non-occupational stress+white shift group, the workers in the night shift+occupational stress group had the higher risk of mental health problems and anxiety (OR=3.14, 95%CI: 1.84-5.38; OR=4.29, 95%CI: 1.36-13.54; P<0.05) . Conclusion: Night shift and occupational stress are the risk factors for the mental health of railway workers, and the interaction between night shift and occupational stress is the most harmful to the mental health of railway workers.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Multi-configuration Dirac-Hartree-Fock calculations of forbidden transitions within the 3d k ground configurations of highly charged ions (Z = 72-83).

Extensive self-consistent multi-configuration Dirac-Hartree-Fock (MCDHF) calculations are performed for the 3s23p63d k (k = 1-9) ground configurations of highly charged ions (Z = 72-83). Complete and consistent datasets of excitation energies, wavelengths, line strengths, oscillator strengths, and magnetic dipole (M1) and electric quadrupole (E2) transition rates among all these levels are given. We have compared our results with the results available in the literature and the accuracy of the data is assessed. We predict new energy levels and transition probabilities where no other experimental or theoretical results are available, which will form the basis for future experimental work.

[Interleukin-1ß and C-reactive protein level in plasma and gingival crevicular fluid in adolescents with diabetes mellitus].

OBJECTIVE: Cytokines produced by various cells are strong local mediators of inflammation. Interleukin-1beta (IL-1ß) and C-reactive protein (CRP) play essential roles in the development and progression of diabetes mellitus (DM). Thus periodontal diseases could be related to DM via the same mediators of inflammation. To evaluate plasma and gingival crevicular fluid (GCF) levels of IL-1ß and CRP in adolescents with DM to further investigate whether DM has an impact on the levels of inflammation factors at an early stage, and to analyze the risk of developing periodontal diseases in adolescents with DM. METHODS: A total of 121 adolescents aged from ten to sixteen years were enrolled, 41 adolescents diagnosed with diabetes mellitus were collected in the DM group, and 80 nondiabetic adolescents as the control group. The periodontal indices of each individual were recorded, including plaque index (PLI), modified bleeding index (mBI), probing depth (PD) and attachment loss (AL). GCF and intravenous blood samples were collected, and CRP and IL-1ß levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) PLI of DM group and control group were 1.23±0.05 and 0.95±0.04 separately, with significant difference (P=0.001). DM group and control group had mBI of 0.80±0.08 and 0.51±0.06 separately, with significant difference (P=0.003). Attachment loss was found in none of the subjects. PDs of DM group and control group were (2.37±0.51) mm and (2.31±0.05) mm separately, and there was no significant difference. (2) CRP in GCF was only detectable in partial of the individuals, with a detectable rate of 22.9% (11/48) in total. The detectable rate of CRP in GCF was significantly higher in DM group (38.5%) than that in control group (4.5%, P=0.006). The plasma level of CRP in DM group [0.23 (0.15, 1.89) mg/L] was higher than that in control group [0.19 (0.12, 4.18) mg/L], but without significance (P=0.776). (3) The plasma levels of IL-1ß in DM group and control group were (14.11±0.57) ng/L and (14.71±0.50) ng/L separately, but there was no significance (P=0.456). GCF levels of IL-1ß in DM group and control group were (12.91±1.95) µg/L and (17.68±3.07) µg/L, without significant difference (P=0.185). CONCLUSION: Periodontitis was not observed in adolescents with DM at an early stage. However, the rising levels of periodontal indices and CRP in GCF, might indicate that adolescents with DM have a higher risk of developing periodontal diseases in the future.

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

OBJECTIVE: To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. METHODS: A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. RESULTS: The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. CONCLUSION: The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

[A study of the diagnostic value of endobronchial ultrasound guide sheath transbronchial lung biopsy combined with virtual bronchoscopic navigation in peripheral pulmonary lesions].

OBJECTIVE: To evaluate the diagnostic value of endobronchial ultrasound guide sheath transbronchial lung biopsy (EBUS-GS-TBLB) combined with virtual bronchoscopic navigation (VBN) in peripheral pulmonary lesions (PPLs). METHODS: Cases with a PPL identified by computed tomography in Affiliated Hospital of Medical College of Ningbo University underwent EBUS-GS-TBLB with or without VBN randomly between Nov. 2014 to Aug. 2015. X-ray guidance was not performed in these cases. The sensitivity and the operation time were evaluated in the 2 groups. RESULTS: A total of 184 patients were enrolled and completed this study. Among them 117 were males and 67 were females. There were 93 cases in the group of EBUS-GS-TBLB with VBN, and 91 in the group without VBN. The diagnostic sensitivity of VBN group was 72.04%(67/93). Among these positive cases, 64.1% cases (43/67) were malignant tumors, and 35.9% cases (24/67) were benign lesions. The mean operation time was (45±10)min. In the group without VBN, the diagnostic sensitivity was 69.23%(63/91), including 33 malignant tumors(52.4%, 33/63), and 30 benign lesions(47.6%, 30/63). The mean operation time was (55±10)min. There was no significant difference between EBUS-GS-TBLB with VBN group and EBUS-GS-TBLB without VBN group in diagnostic sensitivity (χ(2)=0.175, P=0.747). But there was a significant difference in the mean operation time between the 2 groups (t=6.522, P<0.001). EBUS-GS-TBLB was well tolerated. No severe procedure-related complications such as pneumothorax and hemoptysis were observed. CONCLUSION: VBN cannot improve the diagnostic sensitivity, but it can clear the location of lesion, and shorten the operation time. This technique helps to abandon the X-ray guidance. EBUS-GS-TBLB combined with VBN is a safe and effective technique for PPLs.

Long-distance measurement-device-independent quantum key distribution with coherent-state superpositions.

Measurement-device-independent quantum key distribution (MDI-QKD) with decoy-state method is believed to be securely applied to defeat various hacking attacks in practical quantum key distribution systems. Recently, the coherent-state superpositions (CSS) have emerged as an alternative to single-photon qubits for quantum information processing and metrology. Here, in this Letter, CSS are exploited as the source in MDI-QKD. We present an analytical method that gives two tight formulas to estimate the lower bound of yield and the upper bound of bit error rate. We exploit the standard statistical analysis and Chernoff bound to perform the parameter estimation. Chernoff bound can provide good bounds in the long-distance MDI-QKD. Our results show that with CSS, both the security transmission distance and secure key rate are significantly improved compared with those of the weak coherent states in the finite-data case.

[Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases].

Objective: To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer. Methods: In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47-76) years and median body mass index 20.9 (range: 18.3-26.2) kg/m2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results: In this group of patients, the median (range) operative time for ESD was 45 (30-82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10-80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6-26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period. Conclusion: A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.

Association analysis between the -2518MCP-1(A/G) polymorphism and generalized aggressive periodontitis in a Chinese population.

BACKGROUND AND OBJECTIVE: It has been suggested that aggressive periodontitis has a genetic basis. Monocyte chemoattractant protein 1 (MCP-1) plays a critical role in the recruitment of monocytes and the development of periodontitis. The -2518MCP-1(A/G) polymorphism has been implicated as a risk or susceptibility factor for a variety of autoimmune conditions and inflammatory diseases. The intent of this investigation was to study whether the -2518MCP-1(A/G) polymorphism is associated with generalized aggressive periodontitis in the Chinese population. MATERIAL AND METHODS: One hundred and twenty-four patients with generalized aggressive periodontitis and 94 healthy subjects were included in this case-control study. Genomic DNA was isolated from a peripheral blood sample obtained from each subject. Gene polymorphisms of -2518MCP-1(A/G) were analyzed by a standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A logistic regression analysis was performed to test the association between the -2518MCP-1(A/G) genotype (alleles) and generalized aggressive periodontitis with adjustment of the major covariates (gender, age and smoking status). RESULTS: There was no significant association of the -2518MCP-1(A/G) polymorphism with generalized aggressive periodontitis in the unstratified subjects. However, when patients were stratified by gender, the frequency of the G(+) genotype was significantly lower in female patients with generalized aggressive periodontitis compared with female controls (p = 0.036, adjusted odds ratio = 0.3, 95% CI: 0.1-0.9). In female patients with generalized aggressive periodontitis, the probing pocket depth was larger in subjects with the AA genotype than in subjects with the G(+) genotype (5.07 mm vs. 4.30 mm; Z = -2.470, p = 0.014). CONCLUSION: The polymorphisms of -2518MCP-1 may play an important role in determining generalized aggressive periodontitis susceptibility in this cohort of Chinese women.

[Effect of systemic use of amoxicillin and metronidazole during mechanical therapy on the periodontal microorganisms in subgingival plaque and saliva of patients with aggressive periodontitis].

Objective: To explore the effect of systemic use of amoxicillin and metronidazole during mechanical therapy on the clinical parameters of the first molars and periodontal microorganisms in subgingival plaque and saliva in patients with generalized aggressive periodontitis (GAgP). Methods: A total of 23 GAgP patients were recruited from Peking University School and Hospital of Stomatology from January 2006 to December 2009 and then randomly divided into two groups according to random number table: 12 patients received scaling and root planning (SRP) only and 11 patients received SRP combined with systemic administration of antibiotics (amoxicillin and metronidazole for a week after supragingival scaling). Clinical examination of periodontal parameters and collection of saliva and pooled subgingival plaque samples from mesial-buccal sites of 4 first molars were performed before initial therapy and 2, 4 and 6 months respectively after mechanical therapy, and saliva samples were also collected 2 weeks after therapy. Eight different periodontal microorganisms were detected in these samples by PCR. In addition, semiquantitative analysis of red complex microorganisms [Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td)] was performed. Results: Both therapies led to significant decrease of the plaque index (PLI), probing depth (PD) and bleeding index (BI) from mesial-buccal sites of first molars. Meanwhile the PD of antibiotics group [(4.21±1.50), (4.00±1.54), (3.84±1.89) mm of 2, 4 and 6 months respectively after therapy] was significantly lower than the SRP group [(5.29±1.27), (5.30±1.34), (4.98±1.36) mm of 2, 4 and 6 months respectively after therapy] at 3 different time points after mechanical therapy (P<0.05). In the antibiotics group, the quantities of Pg, Tf and Td in subgingival plaque samples (the median quantity decreased to 0.0 ng at 2, 4 and 6 months after therapy) and saliva samples (the median quantity of Tf and Td decreased to 0.0 ng at 2, 4 and 6 months after therapy (P<0.05), and the median quantity of Pg decreased to 16.3, 59.6 and 22.4 ng at 2, 4 and 6 months respectively after therapy) significantly decreased at 3 different time points after mechanical therapy compared with before therapy (P<0.05). While in the SRP group, there were no significant changes in the quantities of Tf and Td in saliva at 2, 4 and 6 months after mechanical therapy (P>0.05) , and the quantities of Tf and Td in subgingival plaque significantly decreased only at 2 months after therapy (P<0.05). Conclusions: SRP combined with systemic administration of amoxicillin and metronidazole could achieve greater improvement in PD of first molars and better control of the amounts of red complex microorganisms in the saliva and subgingival plaque of GAgP patients over a 6-month period.

The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway.

OBJECTIVE: Previous studies have shown that Quinazoline (QNZ) plays extremely important roles in the cellular physiological activity, but it has been rarely examined on cell behavior following intervertebral disc degeneration (IVDD). The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1ß-induced nucleus pulposus (NP) cells degeneration in vitro. PATIENTS AND METHODS: NP were isolated cells from human disc samples collected from patients and the IL-1ß-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL-1ß group (10 µM), QNZ + IL-1ß group (containing 10 nM QNZ and 10 µM IL-1ß). Then, the cell viability was determined by CCK-8 assay, and the levels of collagen I, collagen II, aggrecan, p16, p53, ß-galactosidase (ß-gal), antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG), NF-κB/MAPKs signaling-related proteins and inflammatory factors were examined using Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in NP cells. Finally, the expressions of IL-1ß, IL-6, and TNF-α in the cell supernatants were also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: This study showed that IL-1ß promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and ß-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1ß. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKß, IκBα, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ. CONCLUSIONS: These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NF-κB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future.

[A multicenter survey of the accessibility of essential medicines for children in China].

Objective: To investigate the availability, prices and affordability of essential medicines in pediatric population across China, in the hope of improving rational use of medicines. Methods: A multicenter cross-sectional survey of medicine prices, availability and affordability was conducted in 17 provinces, municipalities and autonomous region across east, south-central part, west and north of China. Data on 42 medicines used in pediatric population, both original and generic, were collected in 55 public hospitals from May 26 to June 2, 2017. Availability was expressed as the percentage of hospitals with stock of the target medicine on the day of data collection,and median price ratio (MPR) was the ratio of price upon investigation to international reference. Based on national minimum daily wage, affordability represents the number of working days needed to earn the expense which covers a standard course using the target medicine. Statistical software SPSS 13.0 was applied for descriptive analysis of availability, MPR and affordability. Results: Mean Availability of original and generic medicine was 33% and 32%, with median MPR being 5.43 and 1.55. Among the 19 medicines with price information for both original and generic product, the median MPR was 7.73 and 2.04 respectively. Regarding the five medicines used to treat four common pediatric diseases (pneumonia,peptic ulcer, congenital hypothyroidism, refractory nephrotic syndrome), the affordability was 0.63 (0.16-6.17) d for generic medicine, and 1.03 (0.16-11.53) d for its original counterpart. Conclusions: The availability to both original and generic products of the 42 medicines used in pediatric population was low in China. The prices of generic medicines seem to be lower and affordability higher than those of original medicines. There is an urgent need to improve the availability and affordability of pediatric medicines.

Family-based association analysis of S100A8 genetic polymorphisms with aggressive periodontitis.

BACKGROUND AND OBJECTIVE: It is known that S100A8, a member of the S100 calcium-binding protein family, is associated with inflammatory diseases, including periodontitis. Our previous population-based study found an association between two polymorphisms, rs3795391 (A > G) and rs3806232 (A > G), in the upstream region of the S100A8 gene and aggressive periodontitis (AgP) in Chinese people. Based on those results, this investigation set out to analyze and corroborate whether the association also exists within families. MATERIAL AND METHODS: Two hundred and four subjects from 73 nuclear families were recruited. All probands and their relatives were diagnosed according to the 1999 classification of periodontal diseases. Anticoagulated peripheral blood samples were collected from all the subjects, and DNA was extracted. The two single nucleotide polymorphisms (SNPs; rs3795391 and rs3806232) were detected and analyzed by standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Analysis of genotype/allele was performed by Family-Based Association Test (FBAT) software ( http://www.biostat.harvard.edu/~fbat/default.html). RESULTS: There was a statistically significant association of the SNP rs3795391 with AgP in the additive genetic model (chi(2) = 3.9836, d.f. = 1, p = 0.0459). Allele A showed significantly preferential transmission to the AgP affected individuals (Z = 1.996, p = 0.0459). The other SNP, rs3806232, showed no significant results in all models. CONCLUSIONS: This family-based association study supports the previous findings that SNP rs3795391 (A > G) of the S100A8 gene might contribute to AgP susceptibility. This is, to our knowledge, the first investigation about AgP using FBAT in genetic analysis.

Elevation of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Systemic levels of C-reactive protein and interleukin-6 have been reported to be elevated in patients with periodontitis compared with periodontally healthy individuals. Most studies included patients with chronic periodontitis and comprised predominantly Caucasians. The aim of this study was to determine the relative levels of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis in China and to examine the relationships between these two inflammatory mediators and clinical parameters, peripheral blood cells and protein variables. MATERIAL AND METHODS: Plasma samples were collected from 84 patients with aggressive periodontitis and from 65 control subjects. Periodontal examination consisted of taking probing depth and attachment loss measurements. The levels of plasma C-reactive protein and interleukin-6 were determined using enzyme-linked immunosorbent assays. RESULTS: The levels of plasma C-reactive protein in patients with aggressive periodontitis were significantly higher than those in control subjects (1.87 vs. 0.52 mg/L). The level of plasma interleukin-6 in patients with aggressive periodontitis was 1.20 pg/mL, higher than that in control subjects (0.08 pg/mL). Multiple linear regression analysis showed that log C-reactive protein was significantly related to severe sites percentage and albumin following correction for age, gender, body mass index and smoking (p = 0.000, p = 0.008, respectively). Log interleukin-6 was found to be significantly correlated with periodontal diagnosis, leukocyte count and level of fasting blood glucose after adjusting for the confounders (p = 0.000, p = 0.009 and p = 0.013, respectively). CONCLUSION: Patients with aggressive periodontitis have significantly elevated levels of plasma C-reactive protein and interleukin-6. These elevated inflammatory factors might potentially increase the risk for cardiovascular events and glucose dysregulation in relatively young individuals.

MIR22HG inhibits cell growth, migration and invasion through regulating the miR-24-3p/p27kip1 axis in thyroid papillary carcinomas.

OBJECTIVE: To explore the underlying mechanism of ncRNA (MIR22HG) in thyroid papillary carcinomas. PATIENTS AND METHODS: 40 pairs of thyroid papillary carcinomas tissues and adjacent normal tissues were collected from patients of the First Affiliated Hospital of Guangxi Medical University, who underwent oral surgery. qRT-PCR was applied to detect the expression of MIR22HG, miR-24-3p and p27kip1 in tissues and cells. Western blot was used to measure the protein level of p27kip1 in tissues and cells. Kaplan-Meier plot was used to analyze the overall survival rates in thyroid papillary carcinomas. Pearson's correlation analysis was used to analyze the correlation relationship among MIR22HG, miR-24-3p and p27kip1 expression. Flow cytometric assay was applied to measure cell apoptosis. Transwell assay was used to assess cell migration and invasion abilities. Luciferase reporter assay was applied to verify the molecular relationships among MIR22HG, miR-24-3p and p27kip1 in thyroid papillary carcinomas. RESULTS: LncRNA MIR22HG and p27kip expressed low while miR-24-3p expressed high in thyroid papillary carcinomas and cells. Overexpression of MIR22HG inhibited cell proliferation, migration and invasion, whereas promoted cell apoptosis in thyroid papillary carcinomas cells. However, these effects were reversed by upregulation of miR-24-3p. Further exploration showed that the promoted effects of miR-24-3p mimics on thyroid papillary carcinomas cells were suppressed by enhancing p27kip1 expression. Meanwhile, MIR22HG induced p27kip1 expression by binding miR-24-3p in thyroid papillary carcinomas. CONCLUSIONS: MIR22HG inhibited cell growth through modulating p27kip1 by decreasing miR-24-3p expression in thyroid papillary carcinomas, providing a new modulate mechanism and therapeutic targets in thyroid papillary carcinomas.

[Screening of microRNAs targeting Notch signaling pathway implicated in inner ear development and the role of microRNA-384-5p].

Objective: To screen the key microRNAs targeting Notch signaling pathway in inner ear and investigate its potential regulating function. Methods: The interaction network and the Core-Notch network, involved with key genes in Notch signal pathway and differential-expressed microRNAs in inner ear, were constructed by bioinformatics methods. The important microRNAs in regulating Notch signaling pathway were screened via topological and GO analysis, followed by in vivo and in vitro investigation. Results: MiRNA-384-5p was identified as a key regulator specifically expressed in mouse brain and inner ear, which could down-regulate Notch1. The Notch1 expression was found significantly down-regulated in miRNA-384-5p-mimic-transfected HeLa cells. The dual-luciferase reporter gene assay further confirmed the effect of miRNA-384-5p on the down-regulation of Notch1 and Dll4 in Notch signaling pathway. Conclusions: The Core-Notch network is constructed to screen microRNAs implicated in inner ear development, and miRNA-384-5p is screened and verified to be target-regulating the Notch signaling pathway, which could be the potential target in the regeneration of impaired hair cells.

The effect of different platelet-rich plasma concentrations on proliferation and differentiation of human periodontal ligament cells in vitro.

OBJECTIVES: The use of platelets and platelet products has become increasingly popular clinically as a means of accelerating endosseous wound healing. It is likely that growth factors released by activated platelets at the site of injury play a role in periodontal regeneration by regulating cellular activity. The purpose of this study was to evaluate the biological effects of platelet-rich plasma (PRP) on human periodontal ligament cells (hPDLCs) in vitro. MATERIALS AND METHODS: Primary cultures of hPDLCs were obtained from healthy premolars. PRP was isolated by two-step centrifugation. Two main growth factors present in the thrombin-activated PRP (platelet-derived growth factor [PDGF-AB] and transforming growth factor-beta1 [TGF-beta1]) were evaluated using ELISA assay. Activated PRP or the combination of recombined human TGF-beta1 (rhTGF-beta1) and PDGF-AB (rhPDGF-AB) were added to hPDLCs in different concentrations to assess cell proliferation and osteogenic differentiation. RESULTS: PRP contained high levels of TGF-beta1 and PDGF-AB. Cell attachment, proliferation and ALP activity were enhanced by addition of PRP or rhTGF-beta1 and rhPDGF-AB combination to the cell cultures, while the stimulatory potency of PRP was much greater than the latter. These stimulatory effects presented in a dose-dependant manner, it seemed that PRP with 50~100 ng/ml TGF-beta1 was an ideal concentration. CONCLUSIONS: PRP can enhance hPDLC adhesion, proliferation and induce the differentiation of hPDLC into mineralized tissue formation cell; thereby contribute to the main processes of periodontal tissue regeneration. For economical and biological reasons, PRP has more clinical beneficial than analogous growth factors.