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Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: −0.001, 95% CI: −0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. −2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. −0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.

Background & Aims Microvascular invasion (MVI) is a critical prognostic factor for operable hepatocellular carcinoma (HCC). This study aimed to explore the performance of circulating tumour DNA (ctDNA) in evaluating MVI status preoperatively. Methods Seventy‐three HCC patients were enrolled and randomly divided into a training cohort and a validation cohort in a 2:1 ratio, and preoperative blood and surgical tissue samples were obtained. Genomic alterations were analysed using targeted deep sequencing with a 1021‐gene panel. Results In training cohort, 260 somatic mutations were identified in 40 blood samples (81.6%). CtDNA mutation was verified in paired tissue sample in 39 patients (97.5%). In univariate analysis, ctDNA allele frequency (AF) and largest tumour diameter were associated with the presence of MVI, but ctDNA AF was the only independent risk factor in multivariate analysis. With the cut‐off value of 0.83%, ctDNA AF determined the presence of MVI with the sensitivity of 89.7% and specificity of 80.0% in the training cohort, and the sensitivity of 78.6% and the specificity of 81.8% in the validation cohort. In preoperative evaluation, ctDNA AF, AFP level and BCLC staging were associated with recurrence‐free survival in both univariate and multivariate analysis. Conclusions CtDNA can serve as an independent risk factor of MVI for operable HCC and help determining precise treatment strategies. The integration of ctDNA in the management of operable HCC may achieve better clinical outcomes.

IntroductionSystemic nutrition and inflammation are the critical factors in cancer initiation, evolution, and progression. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) patients who underwent liver resection.MethodsA total of 202 HCC patients met the criteria and were included in the study. The receiver operating characteristic (ROC) curve was used to calculate the optimal PNI and SII cutoff values. The relationship between PNI/SII and clinicopathologic parameters was analyzed. The effect of PNI and SII on recurrence-free survival (RFS) and overall survival (OS) was investigated by Kaplan-Meier curves and Cox proportional hazards models.ResultsThe areas under the ROC curve for PNI and SII were 0.64 and 0.58. The ideal preoperative PNI and SII cutoff values were 50.25 and 461.5, respectively. Multivariate Cox regression analysis identified that the PNI (P = 0.001) and tumor diameter (P = 0.018) were significant prognostic markers for RFS, and that the PNI (P = 0.049), SII (P = 0.039) and tumor diameter (P = 0.001) were significant prognostic markers for OS. The median RFS in the PNI-low and PNI-high groups was 13.5 months and 23 months (P = 0.001), and that in the SII-low and SII-high groups was 18 months and 15 months (P = 0.03), respectively. The median OS in the PNI-low and PNI-high groups was 24 months and 39 months (P = 0.001), and that in the SII-low and SII-high groups was 36 months and 22 months (P = 0.002), respectively.ConclusionInterestingly, we found that PNI and SII could be important prognostic parameters for HCC patients who under hepatectomy.

Background: It remains uncertain whether vitamin D3 (vitD3) supplementation is beneficial for remission of Crohn's disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) effectiveness was analyzed in Chinese CD patients.Methods: In this retrospective cohort study, moderate-to-severe CD patients, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks, were recorded from January 2014 to December 2019. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention.Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (20.33 vs. 15.07 ng/mL, P < 0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (83.8 vs. 61.6%, P = 0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (7.41 ± 3.0 vs. 6.28 ± 2.75, P = 0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (β = −1.667, P = 0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3 (all P < 0.05), but not in non-deficient vitD3. A total of nine patients (four non-D3-patients and five D3-patients) were selected to determine serum cytokine profiles after 54-week IFX treatment. In non-D3-patients, the decreases of TNF-α and IL-6 at 54-week were more obvious than at baseline (P = 0.032, 0.022, respectively). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P = 0.037).Conclusions: VitD3 supplementation could improve IFX effectiveness in CD patients, especially for patients with vitD3 deficiency. This beneficial effect of vitD3 supplementation probably arose from the up-regulation of IL-10.Trial Registration: NCT04606017.

ObjectiveTo establish a nomogram based on inflammatory indices and ICG-R15 for predicting post-hepatectomy liver failure (PHLF) among patients with resectable hepatocellular carcinoma (HCC).MethodsA retrospective cohort of 407 patients with HCC hospitalized at Xiangya Hospital of Central South University between January 2015 and December 2020, and 81 patients with HCC hospitalized at the Second Xiangya Hospital of Central South University between January 2019 and January 2020 were included in the study. Totally 488 HCC patients were divided into the training cohort (n=378) and the validation cohort (n=110) by random sampling. Univariate and multivariate analysis was performed to identify the independent risk factors. Through combining these independent risk factors, a nomogram was established for the prediction of PHLF. The accuracy of the nomogram was evaluated and compared with traditional models, like CP score (Child-Pugh), MELD score (Model of End-Stage Liver Disease), and ALBI score (albumin-bilirubin) by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsCirrhosis (OR=2.203, 95%CI:1.070-3.824, P=0.030), prothrombin time (PT) (OR=1.886, 95%CI: 1.107-3.211, P=0.020), tumor size (OR=1.107, 95%CI: 1.022-1.200, P=0.013), ICG-R15% (OR=1.141, 95%CI: 1.070-1.216, PConclusionA novel nomogram was established to predict PHLF in HCC patients. The nomogram showed a strong predictive efficiency and would be a convenient tool for us to facilitate clinical decisions.

Teardrop fracture of axis is rarely seen, especially the huge type. The surgical approach is controversial and individualized in the literature. We reported a special case to share our experience of anterior hollow screw fixation combined with posterior unilateral lateral mass screws fixation to treat a huge teardrop fracture of the axis (HTDFA). A 42-year-old male was referred to our department; he presented neck pain after a vehicle accident. Neck movement was limited with no neurological compromise. Cervical x-rays showed a huge tear drop fracture of the anterior–inferior corner of the axis?the lower cervical spine degeneration and poor cervical curvature. Cervical CT confirmed the avulsed ratio of inferior endplate of axis up to 62%. Cervical MRI showed the anterior longitudinal ligament disruption associated with disk injury and instability of C2-3. In order to save the motion segment of C2-3 and decrease the possibility of lower cervical degeneration if C2-3 fusion occurs, a surgical plan involving anterior reduction, hollow screw fixation combined with posterior unilateral mass screws fixation was performed. The 3 months postoperative x-ray and CT scan showed the tear drop fragment had completely healed. The internal fixations were removed timely for 6 months after surgery. The patient had an excellent function of cervical spine without any clinical symptoms. The 12 months postoperative X-ray showed radiographic union of the bony fragment and a good motion range without any instability. We conclude that anterior hollow screw fixation combined with posterior unilateral lateral mass screws fixation can be the treatment of choice for HTDFA.

The present retrospective comparative analysis was conducted to assess the effectiveness of affected-vertebrae fixation versus short-segment fixation to treat thoracic spinal tuberculosis.The present study included 110 patients receiving treatment for thoracic spinal tuberculosis at our hospital from January 2006 to June 2013. All cases involved the use of posterior spinal correction, posterior lateral fusion, internal fixation, anterior decompression, radical debridement, and intervertebral supporting bone grafts. The cases were divided by the scope of posterior internal fixation into the affected-vertebrae fixation group (n = 62) and the short-segment fixation group (n = 48). Statistical analysis was used to compare the clinical effectiveness, laboratory test results, and imaging findings.The mean surgical blood loss, mean operating time, and mean inpatient expenditures were all significantly less in the affected-vertebrae fixation group than in the short-segment fixation group (P0.05). The affected-vertebrae fixation group had a lower mean graft fusion time (5.21 vs. 5.06 months), mean healing time (5.73 vs. 5.91 months), mean degree of correction of thoracic vertebrae kyphosis Cobb angle (16.9° vs. 18.4°), and mean loss of angle (2.6° vs. 2.1°) compared with the short-segment fixation group. However, these differences all lacked statistical significance. Postoperatively, neurological deficits and pain were effectively relieved in all patients, and the lesion had healed at the final follow-up evaluation (≥5 years postoperatively).As long as the surgical indications are strictly observed, posterior affected-vertebrae fixation in posterior-anterior surgery for thoracic spinal tuberculosis is safe, effective, and feasible; entails minimal surgical trauma; and has a lower inpatient cost.

We are very pleased that our research has received peer attention and comments1 , which also enphasized the importance of Microvascular invasion (MVI) in hepatocellular carcinoma (HCC). In Professor Tsai's study2: 322 patients were included. 50 of them had macrovascular invasion (15.53%), 41 received TACE treatment before surgery, and 12 patients had positive postoperative margins.

Chronic respiratory diseases’ (CRDs) impact on re-intubation rate remains unclear. We investigated the association between these factors in mechanically ventilated patients. Data were extracted from the freely available online Medical Information Mart for Intensive Care III database. CRDs were defined according to ICD-9 codes. Generalised linear regression and propensity score matching were performed. Of 13,132 patients, 7.9% required re-intubation. Patients with chronic obstructive pulmonary disease (COPD) had higher re-intubation (OR 2.48, 95% CI 1.83–3.33) and mortality rates (OR 1.64, 95% CI 1.15–2.34) than those without. Patients with asthma had a lower mortality rate (OR 0.63, 95% CI 0.43–0.92) but a similar re-intubation rate to those of patients without. These findings remained stable after propensity score matching and bootstrapping analysis. The association of COPD with re-intubation was significantly stronger in patients with high oxygen-partial pressure (PaO2) or mild disease severity but was independent of carbon dioxide partial pressure. Corticosteroid use was associated with increased re-intubation rates in subgroups without CRDs (OR 1.77–1.99, p 2 or mild disease severity should be carefully monitored as they have higher re-intubation and mortality rates.

Aim: The study aimed to investigate the clinical significance of preoperative alpha-fetoprotein (AFP) and gamma-glutamyl transferase (GGT) (A-G score) on hepatocellular carcinoma (HCC) patients. Methods: A total of 474 solitary HCC patients were included. Survival analysis was evaluated by Kaplan-Meier method. Prognostic factors were analyzed in a multivariate model. The comparison of the predictive value of AFP, GGT, and A-G score was performed by receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Results: Of the 474 patients, 137(28.9%), 241(50.8%), and 96(20.3%) patients were assigned to A-G score 0, 1, and 2, respectively. In multivariate analysis, A-G score, tumor size, microvascular invasion, tumor differentiation, satellite lesion, and state of HBV infection were independently predictive factors for RFS of solitary HCC patients. The A-G score could significantly stratify solitary HCC patients with a distinguished prognosis. The 1-, 3-, and 5-year RFS and OS among patients with A-G score 1 was better than that of patients with A-G score 2 and worse than that of patients with A-G score 0(all p < 0.05). Based on the result from the ROC analysis and DCA analysis, the A-G score appeared to be superior to either AFP or GGT alone in the prediction of prognosis of solitary HCC patients. In the subgroup analysis, the A-G score could accurately predict the prognosis of solitary HCC patients without MVI or with liver cirrhosis. Conclusions: Preoperative A-G score could effectively and simply predict prognosis of solitary HCC patients after hepatectomy, especially for those with non-MVI solitary HCC or those with liver cirrhosis.

Background Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. Methods This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. Results In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98–0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69–0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03–0.253, P 0.5 (OR: 1.04, 95% CI: 0.96–1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96–0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. Conclusions The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

BACKGROUND Type 2 diabetes mellitus (T2DM) and estrogen deficiency both predispose fracture patients to increased risk of delayed union or nonunion. The present study investigated the effects of strontium ranelate (SR) on fracture healing in ovariectomized (OVX) diabetic rats. MATERIAL AND METHODS A mid-shaft fracture was established in female normal control (CF), diabetic (DF), and OVX diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after fracture. Fracture healing was evaluated using radiological, histological, immunohistochemical, and micro-computed tomography analyses. RESULTS At 3 weeks after fracture, radiological and histological evaluations demonstrated delayed fracture healing in the DF group compared with the CF group, which was exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD, BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in the DOF group. All these changes were prevented by insulin alone or combined with SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3 weeks after fracture. CONCLUSIONS These results demonstrated delayed fracture healing with preexisting estrogen deficiency and T2DM. While insulin alone and combined with SR were both effective in promoting bone fracture healing in this model, their combined treatment showed significant improvement in promoting osteogenic marker expression, but not of the radiological appearance, compared with insulin alone.

Background Osteoporotic thoracolumbar burst fracture (OTLBF) is common in seniors. Due to the fracture of the posterior vertebra and spinal canal occupancy, the risk of cement leakage and spine injury is high in OTLBF patients, thus the application of vertebroplasty and kyphoplasty is limited in these patients. This study aims to investigate the efficacy and safety of the modified percutaneous kyphoplasty (MPKP) in the treatment of OTLBF. Methods Clinical data of the OTLBF patients treated with MPKP and the osteoporotic thoracolumbar compression fracture (OTLCF) patients undergone PKP from January 2014 to June 2016 were collected. The key procedure of the MPKP was to fill the bone cavity with gel-foam by the first balloon inflation and to press the gel-foam by a second balloon inflation. Pain intensity, Oswestry disability index (ODI), and bone cement leakage of the patients in the two groups were analyzed. Results In the burst fracture group, the overall spinal canal occupancy was relatively low, and the maximum occupancy was 1/3 of the sagittal diameter of the spinal canal. The surgical duration was longer in the burst fracture group (39.0 ± 5.0 min with 95% CI: 37.7, 40.3) than in the compression fracture group (31.7 ± 4.3 min with 95% CI: 31.1, 32.3), and the difference between the two groups was statistically significant (Z = -8.668 and P = 0.000). Both the Oswestry disability index (ODI) and the visual analog scales (VAS) were apparently improved, but there was no significant difference between the two groups. Cement leakage occurred in 13 out of the 53 cases (24.5%) in the burst fracture group and 35 out of the 193 cases (18.1%) in the compression fracture group, and there was no significant difference between the two groups (Z = − 1.038 and P = 0.299). Neither group had consequential symptoms, such as spinal cord lesion, pain, and numbness of the peripheral nerve. Conclusion Similar to the efficacy of PKP in the treatment of OTLCF, MPKP efficiently reduced the cement leakage rate and improved the safety of the surgery, although it prolonged the surgical duration and introduced more surgical steps.

Background This study aimed to investigate the roles of CYP3A4 and CYP11A1 variants in ischemic stroke (IS) susceptibility among the Han Chinese population. Methods Four hundred seventy-seven patients with IS and 493 healthy controls were enrolled. Seven single-nucleotide polymorphisms (SNPs) of CYP3A4 and CYP11A1 were genotyped by Agena MassARRAY. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender. Results We found that CYP3A4 rs3735451 (OR = 0.81, p = 0.039) and rs4646440 (OR = 0.72, p = 0.021) polymorphisms decreased the risk of IS. CYP3A4 rs4646440 (OR = 0.74, p = 0.038) and CYP11A1 rs12912592 (OR = 1.58, p = 0.034) polymorphisms were correlated with IS risk in males. CYP3A4 rs3735451 (OR = 0.63, p = 0.031) and rs4646440 (OR = 0.57, p = 0.012) possibly weaken the IS susceptibility at age > 61 years. Besides, CYP3A4 rs4646437 (OR = 0.59, p = 0.029), CYP11A1 rs12912592 (OR = 1.84, p = 0.017) and rs28681535 (OR = 0.66, p = 0.038) were associated with IS risk at age ≤ 61 years. CYP11A1 rs28681535 TT genotype was higher high-density lipoprotein cholesterol level than the GT and GG genotype (p = 0.027). Conclusions Our findings indicated that rs3735451, rs4646440, rs4646437 in CYP3A4 and rs28681535 in CYP11A1 might be protective factors for IS, while CYP11A1 rs12912592 polymorphism be a risk factor for IS in Chinese Han population.

Gout is a rare cause of patellar fracture, with few documented cases. We report a case of gout tophi in the patella, the severe transverse fracture resulting from minor trauma. The patient was managed by the same treatment principles used for patients with nonpathologic patella fractures. We preformed excising the mass, fixing the bone fragment and filling in bone defect with allograft bone. Union of the fracture was seen at three months follow-up. The patient has recovered completely and returned to his former work after 3 months postoperatively.

Background Stroke is a serious cardiovascular disease and is also the leading cause of long-term disability in developing and developed countries. Because matrix metalloproteinase-9 (MMP-9) is associated with the risk of many cardiovascular diseases, we investigated the relationship between single nucleotide polymorphisms (SNPs) in MMP-9 and the risk of Ischemic stroke (IS) in a southern Chinese Han population. Methods This study included 250 stroke patients and 250 healthy controls. Genotyping was performed using the Agena MassARRAY system, and chi-squared tests and genetic models were used to evaluate the associations between MMP-9 SNPs and the risk of IS. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age. Results Polymorphism rs3787268 was associated with increased the risk of IS. Specifically, the genotype “G/A” significantly correlated with IS risk in the co-dominant model [odds ratio (OR) = 1.62; 95% confidence interval (CI) = 1.10–2.41; p = 0.035)], while genotypes “G/A” and “A/A” may increase the risk of IS based on the dominant model (OR = 1.62; 95% CI = 1.12–2.35; p = 0.0097). This SNP was also significantly associated with IS risk in the log-additive model (OR = 1.33; 95% CI = 1.03–1.70; p = 0.026). Conversely, haplotype “C/G” appears to reduce the risk of IS (OR = 0.71; 95% CI = 0.54–0.95; p = 0.019). Conclusions Our study showed that the rs3787268 locus in the MMP-9 gene may increase risk of IS in a southern Chinese Han population and thus provide insight into the IS pathogenesis.

Background: Microvascular invasion (MVI) is a critical prognostic factor for operable hepatocellular carcinoma (HCC). This study aimed to explore the performance of circulating tumor DNA (ctDNA) in evaluating MVI status preoperatively. Methods: Forty-nine HCC patients were enrolled and clinicopathological characteristics were collected. Preoperative blood and surgical tissue samples were obtained, and genomic alterations were analyzed using targeted deep sequencing with a 1021-gene panel. Findings: Totally 260 somatic mutations were identified in 40 blood samples (81*6%). The most recurrent mutant genes included TP53 (55*1%), TERT (16*3%), AXIN1 (12*2%), LRP1B (10*2%) and CTNNB1 (10*2%). CtDNA mutation was verified in paired tissue sample in 39 patients (97*5%). In univariate analysis, ctDNA allele frequency (AF) and largest tumor diameter were associated with the presence of MVI, but ctDNA AF was the only independent risk factor in multivariate analysis. With the cut-off value of 0*83%, ctDNA AF determined the presence of MVI with the sensitivity of 89*7% and specificity of 80*0%. Although MVI status, ctDNA AF, AFP level, Edmondson-Steiner classification and BCLC staging were associated with recurrence-free survival, MVI was the most powerful and significant prognostic factor in Cox regression analysis. Interpretation: CtDNA can serve as an independent risk factor of MVI for operable HCC and help deciding precise treatment strategies and ultimately better clinical outcomes. Funding Statement: This study was funded by the National Nature Science Foundation of China (No. 81771932) and Tianqing Liver Disease Research Fund of the China Hepatitis Prevention Foundation (No. TQGB20180120). Declaration of Interests: The authors declare no any potential competing interest. Ethics Approval Statement: All patients provided written informed consent. The study was approved by the Ethics Committee of Xiangya Hospital affiliated to Central South University (No. 201703377).

Infantile digital fibromatosis is a rare, benign fibrous tumor among infants usually limited to fingers and toes. Most cases present themselves with round eosinophilic inclusion bodies of different sizes, similar to erythrocyte in the parakarytoplasm. Although infantile digital fibromatosis had been observed with a tendency of spontaneous regression after a rapid phase of growth in some reports, the recurrence rate of early surgical intervention remains high. And the mechanism of recurrence is still unknown. Human papillomavirus (HPV), as a circular icosahedral double-stranded DNA virus, is famous for its remarkable significant correlation with cervical cancer. However, the reports about the possible relationship of recurrent infantile digital fibromatosis and HPV infection are rare and inconsistent. Here, we report a recurrent case of infantile digital fibromatosis after surgical resection. Pathological biopsy of the recurrent site not only identified the diagnosis of infantile digital fibromatosis again, but found the sign of HPV infection. Family history indicated that the patient's grandmother had a history of verruca plana. After complete resection of recurrence, the tumor recurred again and the case is still being followed up. The unique case may serve as a clue to the pathogenesis of the relationship between recurrent infantile digital fibromatosis and HPV infection.

Background: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. Methods: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. Results: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. Conclusions: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.

The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies.

The present study aimed to investigate the effects of glycogen synthase kinase-3β (GSK-3β) on the expression levels of receptor activator of nuclear factor (NF)-κB (RANK), RANK ligand (RANKL) and NF-κB in the renal tissues of rats modeling diabetic nephropathy (DN). The rats were allocated at random into three groups, as follows: Normal control group (NC), the DN model group (DNM group) and the DN model lithium chloride (LiCl) intervention group (DNI group). Urinary proteins were examined by staining with the Coomassie Brilliant Blue dye for 24 h. Histochemical analyses of kidney tissue sections were conducted using hematoxylin and eosin staining, after which the kidney pathology of the rats was observed. In addition, the mRNA and protein expression levels of GSK-3β, RANK, RANKL and NF-κB in the renal tissues were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. As compared with the NC group, the level of urinary protein was significantly increased in the DNM group (P

Background: The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to investigate the impact of clinical stage on radiation doses to organs at risk (OARs) in NPC. Material and Methods: One hundred and forty-eight patients with newly diagnosed and untreated NPC were prospectively enrolled. Based on the anatomic definition and pathogenesis of radiation induced injury, a total of 28 OARs surrounding the nasopharynx were contoured on axial computed tomography (CT) planning images in each patient. Dose-volume histograms, as well as the mean and maximal doses for each structure, were calculated. Results: Radiation doses to 15 OARs (including the brain stem, temporal lobe and eye) were positively correlated with T stage, the radiation doses to 13 OARs (including the brachial plexus, parotid and thyroid) increased significantly with N stage, and the radiation doses to the spinal cord and mandible had no association with T or N stage. Based on the characteristic of excess rates, 9 OARs (e.g. spinal cord, eye, trachea, and et al.) met tolerance doses easily in all stages, 9 OARs (e.g. brain stem, temporal lobe, brachial plexus, and et al.) easily in early stages but with difficulty in advanced stages, and 10 OARs (e.g. cochlea, parotid, thyroid, and et al.) with difficulty in all stages. Conclusions: The radiation doses to most of OARs are associated with T or N stage, and there are three kinds of patterns for them: 1) meet tolerance doses easily in all stages; 2) meet tolerance doses easily in early stages but with difficulty in advanced stages; and 3) meet tolerance doses with difficulty in all stages.

4593 Background: Resection is a major method for early-stage liver cancer patients. Unfortunately, there still a few patients with post-operation recurrences. Circulating tumor DNA (ctDNA) had been reported as a biomarker in reflecting tumor load and treatment efficacy in some cancer species. Here, we report an application of ctDNA in the perioperative period of liver cancer using targeted sequencing with a 1021-gene panel. Methods: 97 patients diagnosed with liver cancer were enrolled in this study. Postoperative peripheral blood samples were collected within 7 days after surgery and analyzed using hybridization capture based NGS ERSeq method from all patients. Whether a mutant gene was detected in the peripheral blood was defined as ctDNA(+) and ctDNA(-), respectively. Results: Multivariate Cox analysis showed that the post-operation ctDNA was an independent poor prognostic predictor (AFP, RR: 1.0002, 95% Cl: 1.0001-1.0002; ctDNA, RR: 3.738, Cl: 1.872-7.691). 21 patients were ctDNA(+), and all of them had recurrenced (21/21, 100%), while 76 patients were ctDNA(-), and only 12 (12/76, 15.8%) patients had recurrenced. The median disease-free survival time was 5.0 months in ctDNA(+) group and the ctDNA(-) group had not reach the median time (Log-rank test, P < 0.0001). ctDNA combined with AFP would effectively predict the prognosis of patients after surgery. AFP(H) ( > = 400 ng/mL) and ctDNA(+) patients have the worst prognosis and all of the patients had relapsed, while AFP(L) ( < 400 ng/mL) and ctDNA(-) patients had the best prognosis, with less than 20% of patients had relapsed (Log-rank test, P < 0.0001). The median disease-free survival time was 2.0, 6.0 and 7.0 months in ctDNA(+)-AFP(H) (n = 8), ctDNA(-)-AFP(H) (n = 30) and ctDNA(+)-AFP(L) (n = 13) groups, respectively, while ctDNA(-)-AFP(L) group (n = 46) had not reach the median time statistically (Log-rank test, P = 0.0364). Conclusions: In summary, Perioperative ctDNA detection has great potential value clinically, and it also suggests that patients with positive ctDNA after surgery should receive some adjuvant treatments as soon as possible to improve the survival time.

BACKGROUND: Circulating cell-free DNA (cfDNA), which is present in the blood, is related to the apoptosis and necrosis of cancer cells; inflammation also influences the total plasma level of cfDNA. However, the total plasma cfDNA level has not been investigated in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who experience cancer and HBV infection at the same time. The aim of the study was to investigate total plasma cfDNA in patients with HBV-related HCC. METHODS: HBV-related HCC patients were included from January 2018 to May 2019. All patients underwent hepatectomy and were diagnosed with HCC by histopathology. Peripheral blood samples were obtained preoperatively, and the levels of total plasma cfDNA were quantitated by a fluorometric double-stranded DNA (dsDNA) assay. We examined the correlation between cfDNA and clinical parameters, and recurrence-free survival was evaluated using Kaplan-Meier curves. RESULTS: Forty-eight HBV-related HCC patients were included. The average age in years was 50.90±13.15, and the mean albumin level was 41.63±5.38 g/L. HBV-DNA, Child-Turcotte-Pugh (CTP) class, TNM stage, tumor number and vascular invasion showed a relationship with total plasma cfDNA (P

BACKGROUND The aim of this study was to investigate the influence of genetic polymorphism of cholesteryl ester transfer protein (CETP) gene polymorphism -629C/A on the therapeutic effect of atorvastatin and clinical outcome in Han Chinese patients with coronary heart disease (CHD). MATERIAL AND METHODS From October 2011 to December 2012, 348 patients with angiographically confirmed CHD were recruited. CETP gene polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-1inked immunosorbent assay (ELISA). Lipid 1evel in all patients was determined at baseline and after 12 months of treatment with 20 mg/d of atorvastatin. All the patients were followed-up at least 12 months. Major adverse cardiac events, including death, non-fatal infarction, revascularization, and stroke (MACE), were recorded. RESULTS The frequency of the -629A allele was 0.412. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels (P=0.026) and higher high-density lipoprotein cholesterol (HDL-C) levels (P=0.035). After 12 months of atorvastatin therapy, carriers with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C) (P

4017 Background: Diffuse-type or mixed-type gastric adenocarcinoma is associated with poor prognosis, and more effective treatment is needed. In Asia, S-1 plus cisplatin (SP) is the standard first-line chemotherapy regimen for advanced gastric cancer. Nevertheless, some clinical data suggested that oxaliplatin-based chemotherapy might be more efficacious and more tolerant than cisplatin-based chemotherapy. Methods: This trial is a multicenter, randomized, parallel-group, open-label, phase 3 trial in China. Patients aged 18-75 years, with PS 0-2, adequate organ function, histology confirmed, unresectable, advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA were randomized 1:1 to S-1 plus oxaliplatin group (SOX) (S-1: 40-60mg bid on d1-14, q3w; oxaliplatin: 130 mg/m2 on d1, q3w) or SP group (S-1: 40-60mg bid on d1-14, q3w; cisplatin: 60 mg/m2 d1, q3w). The primary endpoint was overall survival (OS) in the full analysis set (FAS). The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and safety. Results: Between Jul 2013 and Jul 2018, 576 patients were randomized and 558 initiated treatment (279 patients/group). The median number of chemotherapy cycles was four in each group. In the FAS, the SOX group showed improved OS (13.0 vs. 11.8 months, HR = 0.764, 95% CI: 0.636-0.918), PFS (5.7 vs. 4.9 months, HR = 0.752, 95%CI: 0.632-0.895), and TTF (5.2 vs. 4.7 months, HR = 0.763, 95%CI: 0.641-0.909) compared with the SP group. In terms of grade≥3 adverse events, SOX showed lower occurrences of neutropenia (10.0% vs. 22.9%), leukopenia (9.7% vs. 21.9%), anemia (4.3% vs. 14.3%),vomiting (3.9% vs. 10.4%), nausea (2.2% vs. 10.4%), anorexia (2.2% vs. 6.8%), and febrile neutropenia (2.5% vs. 6.8%) than SP (all P < 0.05). The occurrence of grade≤2 sensory neuropathy(41.6% vs. 12.2%, P < 0.001)was higher with SOX than with SP. Conclusion: Compared with SP, SOX was more effective and less toxic (except neurosensory toxicity ) in patients with previously untreated advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA. Clinical trial information: NCT01824459.

Background Cell transplantation of human cord blood mononuclear progenitor cells (HCBMCs) is a new treatment that could restore cardiac functions after acute myocardial infarction (AMI). We hypothesize that multiple doses of HCBMCs might increase homing of transplanted cells to infarcted region, and improve outcome of AMI via inhibition of ischemic-induced inflammatory responses. Methods and results HCBMCs were injected intravenously to rabbits that previously underwent ligation of left anterior coronary artery (LAD). Single dose of HCBMCs was intravenously delivered on the 7th day or multiple doses of HCBMCs were delivered on the 7th, 9th, 11th and 13th day after AMI. Homing of HCBMCs was determined by 5-bromodeoxyuridine (BrdU) labeling. The amount of grafted cells homed and retained in the infarcted area was significantly increased in the rabbits that received multiple doses. More viable cardiomyocytes and less collagen deposition were observed also in the group with more injections. Cardiac functions were assessed by echocardiography and hemodynamics. Multiple doses of HCBMCs showed significant benefits in preservation of cardiac functions. In infarcted myocardium, multiple transplantations of HCBMCs showed a significant increase in the myocardial level of anti-inflammatory IL-10 and a marked decrease in the level of the pro-inflammatory IL-6. Conclusions Multiple injections of HCBMCs markedly increased the amount of grafted cells, beneficially improving cardiac functions after AMI. The findings suggest that multiple doses of HCBMCs might be a novel strategy in the cell therapy for AMI.

We have recently demonstrated that endothelial progenitor cells (EPCs) inhibit AngII-induced proliferation of vascular smooth muscle cells (VSMCs) by inactivating MAPKs and NF-κB signaling pathway and reducing expression of oncogene c-myc and c-fos. The inhibitory effect of EPCs on VSMCs is associated with paracrine mechanism. However, the potential mechanism of EPCs on the regulation of AngII-induced proliferation of VSMCs was unknown. Calcitonin gene-related peptide (CGRP) could inhibit AngII-induced proliferation and transformation of VSMCs. However, it has not been known whether CGRP released from EPCs is a potential regulator in regulation of AngII-induced proliferation of VSMCs. Early endothelial progenitor cell-conditioned medium(E-EPC-CM) was pre-incubated with functional blocking antibodies against CGRP for 1 h or VSMCs was preteated with CGRP(837)(CGRP receptor antagonist) for 1 h before VSMCs were pretreated with CM for 30 min. DNA synthesis ability, total protein levels, cell survival, signal transduction, and expressions of c-myc and c-fos of VSMCs induced by AngII (10(-6)mol/l) were detected to assess the role of CGRP in AngII-induced proliferation of VSMCs. E-EPC-CM could significantly inhibit AngII-induced DNA synthesis ability, total protein levels, cell survival, phosphorylation of ERK, JNK, p38, p65, and expressions of c-myc and c-fos compared with the control group(P < 0.05). However, Pretreatment with anti-CGRP antibody and CGRP(837) could significantly weaken the inhibitory effect of E-EPC-CM on proliferation of VSMCs induced by AngII (P < 0.05). EPCs exert anti-proliferative effects on VSMCs mediated by the release of CGRP.

Summary Introduction To investigate the cardioprotective effect of MicroRNA-21 (miR-21) in murine myocardial infarction (MI). Methods Forty C57BL/6 male mice were divided into sham group, MI group, LV-GFP group, and miR-21 group. Mice in the MI group, LV-GFP group, and miR-21 group were subjected to MI by left anterior descending artery (LAD) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR-21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR-21 and lentivirus that did not express miR-21 were transfected into mice left ventricular cavity of miR-21 group and LV-GFP group, respectively. Cardiac function, MI size, miR-21 expression, collagen I level, fibronectin content, number of α-SMA-positive cells, number of apoptotic cells, apoptosis-related factors were compared between the three groups. Results Compared with sham group, miR-21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in the miR-21 group improved compared to the LV-GFP group. In miR-21 group, myocardial infarct size reduced by 36.9% in comparison with LV-GFP group. Compared to sham group, miR-21 expression in the miR-21 group and LV-GFP group decreased significantly. In the miR-21 group, collagen I level, fibronectin content and number of α-SMA-positive cells of miR-21 decreased significantly compared to the LV-GFP group. The number of apoptotic cells in the MI areas of the miR-21 group was significantly less than the LV-GFP group. Compared with the LV-GFP group, Bcl-2 level and the ratio of Bcl-2 to Bax were significantly increased, and the levels of Bax and Caspase-3 decreased. Conclusions Our results suggest miR-21 is an important regulatory molecule in the pathophysiology of MI.

Background Delayed M1 toward M2 macrophage phenotype transition is considered one of the major causes for the impaired healing after myocardial infarction (MI). While searching for molecules that modulate M1 and M2 macrophage polarization, we identified collapsin response mediator protein-2 (CRMP2) as a novel molecule involved in macrophage polarization to M1. In this study, we evaluated the effect of silencing CRMP2 on macrophage polarization, inflammation and fibrosis post myocardial infarction. Methods CRMP2 expression was assessed with Western blotting or immunohistochemistry. Macrophage phenotypes were measured with flow cytometry, quantitative real-time PCR (qPCR), Western blotting or immunohistochemistry. CRMP2 siRNA was delivered into the macrophages infiltrated in the wound of ApoE−/− mice through lipidoid nanoparticle, and fibrosis, leukocyte infiltration and inflammation parameters were measured with qPCR. Infarct size was measured with Masson’s trichrome staining. Echocardiography was performed to assess ventricular systolic dimension, left ventricular diastolic dimension, anterior wall thickness and posterior wall thickness. Student’s t-test (for 2 groups) and ANOVA (for > 2 groups) were used for statistical analyses. Results CRMP2 was expressed in a higher level in M1 macrophages than M2 subsets, and CRMP2 RNA interference (RNAi) resulted in a switch of bone marrow-derived macrophages from M1 to M2 phenotype. High level of CRMP2 was also observed in the macrophages infiltrated in the infarct area 3 days post MI in both wildtype (WT) and ApoE−/− mice, and the expression of CRMP2 retained in the infiltrated macrophages of ApoE−/− mice but not in that of WT mice 10 days after MI. Nanoparticle-mediated delivery of CRMP2 siRNA to ApoE−/− mice with MI resulted in dramatic switch of wound macrophages from M1 to M2 phenotype, marked decrease in inflammation and fibrosis, and significant attenuation of post-MI heart failure and mortality. Conclusion CRMP2 is highly expressed in M1 macrophages and silencing CRMP2 reprograms macrophage phenotype and improves infarct healing in atherosclerotic mice.

In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from fluoride toxicity, we treated PC12 cells by different concentrations of fluoride (0.1-100 ppm) for 48 h, and exposed rats to high doses of fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neurotoxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR alpha3, alpha7, beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of fluoride or rat brains with chronic fluorosis. The decreases of nAChR alpha3 and alpha7 subunit proteins in PC12 cells resulted from fluoride toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by fluoride toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.

Diabetic patients suspected of having osteomyelitis secondary to foot ulcers underwent scintigraphic imaging with Sulesomab, an anti-granulocyte antibody Fab' fragment labeled with technetium-99m. Among 122 patients who had osteomyelitis confirmed or excluded by histopathologic and/or microbiologic techniques, Sulesomab had a 91% sensitivity, a 56% specificity, and an accuracy of 80%. One planar imaging session was usually sufficient for diagnosis, typically requiring 20-30 minutes of camera time 1-2 hours after injection. Compared with ex vivo autologous white blood cell (WBC) scans, Sulesomab performed comparably but with significantly greater sensitivity (92% vs. 79%; P < .05). Sulesomab results were more sensitive than radiography (90% vs. 62%; P < .05) and more specific than bone scans (50% vs. 21%; P < .05) and would have altered management plans in most patients. No related adverse events occurred, and there was no induction of human anti-mouse antibody. Sulesomab is an effective and rapid imaging agent that is diagnostically comparable or superior to WBC scans in this setting, with significant advantages in safety and ease of use.

Nitric oxide synthase (NOS)-immunoreactive neurons were identified in the rat kidney by using an antibody against type Ia NOS and the avidin-biotin complex immunoperoxidase method in whole kidneys examined in 100 microns serial sections. The histochemical method for demonstration of the nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) was also used to characterize NOS-containing neurons. All somata showing NOS immunoreactivity also displayed NADPH-d activity. The greatest number of neuronal somata were observed in groups at the wall of the renal pelvis and in the angular space formed by the pole of the renal parenchyma and renal pelvic wall. They were also seen at the renal hilus close to the renal artery and along the interlobar vasculature. The size of the neuronal somata in the 35-day-old rat ranged from 13.6 to 34.8 microns, with a mean size of 21.52 +/- 4.81 microns. Seventy percent, however, ranged in size from 17.8 to 26.8 microns. The shape of the neuronal somata also varied, with the majority having an ovoid or round shape. The distribution of the postganglionic fibers was investigated by means of the camera lucida. Postganglionic fibers projected into the wall of the renal pelvis and/or to the interlobar arteries extending to the arcuate arteries and to the beginning of the afferent arterioles. The NOS-immunoreactive neurons may have a vasodilator and relaxing function on the renal pelvic wall and vasculature. In addition, the presence of NOS-containing nerve fibers in nerve bundles, which are known to have predominantly vasomotor and sensory fibers, suggest that they may have a possible modulatory role on renal neural function.

Background Citrate is the anticoagulation of choice in apheresis procedures. Citrate anticoagulation results in a short-term increase in serological markers of bone turnover, with uncertain clinical significance. Aim To understand the effect of calcium supplementation on serological bone turnover markers during an acute citrate load as a mimic of citrate anticoagulation during apheresis procedures. Methods A placebo-controlled, crossover study was conducted in 22 healthy volunteers. Volunteers received a standardized citrate load at a fixed dose of 1.5 mg/kg of body weight/min for 80 min for three times and a single placebo infusion as a control. Each intervention was separated by a wash-out interval of 2 to 3 weeks. During two citrate infusions, volunteers received an additional calcium supplementation, consisting of either oral administration of calcium carbonate or an i.v. bypass infusion of calcium gluconate. Serial blood samples were collected for the determination of ionized calcium (iCa), intact parathyroid hormone (iPTH) and markers of bone remodeling, C-telopeptide of type 1 collagen (CTX) and osteocalcin (OC). Results The infusion of citrate without calcium supplementation resulted in an increase in the bone formation marker OC and the bone resorption marker CTX, in addition to the changes in iPTH and iCa. The administration of calcium by either oral administration or as an i.v. bypass infusion attenuated the observed changes in CTX, but showed no effects on the elevation of the bone formation marker OC. There was no difference in the attenuation of CTX between the two calcium formulations. However, the i.v. application of calcium gluconate had a superior effect in reducing the change of serum iPTH and iCa as compared to the oral administration of calcium carbonate. Conclusions Calcium supplementation is an effective method in damping the citrate-related transient increase of the serological bone resorption marker CTX. As a mimic for the citrate-based apheresis procedure, our data may enforce the prophylactic application of calcium supplementation to attenuate the short-term elevation of bone resorption related to an acute citrate load.

To investigate the application of adipose-derived stem cell (ADSC) technology in the treatment of stress incontinence.The vaginal balloon dilatation method was used to establish an animal model of stress incontinence (in 20 female Sprague-Dawley rats), which was further examined by urodynamics and histology. Endogenous rat ADSCs were collected and induced into myoblasts with 5-Aza induction technology in vitro. The identity of myoblasts was confirmed through immunofluorescence labeling with desmin and myosin. Induced cells were injected into the posterior urethral muscularis in the bladder neck of animals with stress incontinence. The effects were examined after 1 and 3 months by urodynamics and histology. Untreated ADSCs were also implanted as a method of control.Both maximal bladder capacity and leak point pressure significantly increased after 1 and 3 months postimplantation, compared with the control (P.05). Increased thickness of inferior muscularis in urethral mucosa and a greater number of large longitudinal muscle bundles were observed. Increased numbers of myoblasts appeared under the mucosa, as demonstrated by the immunochemistry analysis of alpha-smooth actin.ADSCs have the ability of differentiating into multiple lineages, including myoblasts. This ability to induce myoblasts can be used to treat stress incontinence, with the advantages of minimal invasion and faster recovery.

The present study was to determine whether clonidine could induce calcitonin gene-related peptide (CGRP) production and the underlying mechanisms. Human umbilical vein endothelial cells were treated with clonidine and the dose-effect or time-effect relationship of clonidine on CGRP production was examined. Yohimbine (a alpha(2)-adrenoceptor blocker) and L-NAME (an antagonist of nitric oxide synthase, NOS) were chosen to explore the role of alpha(2)-adrenoceptor and nitric oxide pathway in the effect of clonidine on endothelial cell-derived CGRP production. The level of CGRP mRNA or protein was detected by Real Time-PCR or radioimmunoassay. Nitric oxide content was measured by nitroreduction assay. The study showed that clonidine was able to induce CGRP mRNA (alpha- and beta-isoforms) expression in a dose-dependent manner in endothelial cells. The effect of clonidine on endothelial cell-derived CGRP synthesis and secretion was attenuated in the presence of yohimbine. L-NAME treatment could also inhibit clonidine-induced CGRP synthesis and secretion concomitantly with the decreased NO content in culture medium. These results suggest that clonidine could stimulate CGRP synthesis and secretion in endothelial cells through the activation of alpha(2)-adrenoceptor, which is related to the NO pathway.

The treatment and relapse rate of genital warts are significant problems. The aim of this observational study was to assess the efficacy of holmium laser treatment of genital warts. A total of 1500 outpatients with genital human papillomavirus-induced lesions presenting from August 2002 to June 2005 were treated with holmium laser. The effects and side-effects of treatment were observed and analysed. Of this large cohort, lesions were excised at the first visit in 1488 cases. Twelve cases were treated a second or third time in the event that the lesions were too large to be removed at the first visit. The incidence of side-effects and complications after treatment with holmium laser was found to be low. Almost all warts can be excised at first treatment by holmium laser therapy with little bleeding during the treatment.

Stab wounds are the main type of penetrating cardiac injury in China and they have a fairly good prognosis when the patient receives expeditious and appropriate management. The objective of this study is to present the experience of managing the patients with penetrating cardiac injuries. A retrospective study involving 82 cases with penetrating wounds of the heart in the past 16 years was carried out. Stab wounds accounted for 86.58% of this series (71 of 82 patients). All 82 cases were treated operatively. The amount of preoperative infusion as fluid resuscitation for shock was less than 1,000 ml in 65.85% of the present study. Only in three patients was preoperative pericardiocentesis performed, yielding a false-negative result in one. Six patients sustaining cardiac arrest soon after arrival were subjected to emergency room thoracotomy (ERT), and five of them survived. The overall survival rate was 96.34%. One patient died of exsanguination due to injury of multiple chambers; of the remaining 2 deaths after operation 1 was associated with abdominal injuries and the other with failure of cerebral resuscitation. From the experience reported in this study, early establishment of diagnosis and prompt thoracotomy against time are the fundamental factors affecting the outcome of penetrating cardiac injuries. Preoperative massive transfusion and pericardiocentesis are not advocated.

Liver trauma, the main cause of death in patients suffering abdominal injury, remains an unresolved problem, especially in its most severe forms. The objective of this study was to probe effective surgical procedures and improve the outcome for patients with severe hepatic injury. A retrospective study of 348 patients with hepatic trauma seen in our institution during the past 12 years was carried out. Of these 348 patients, 259 (74.4%) underwent surgery. To manage severe liver trauma (American Association for the Surgery of Trauma grade III to grade V), procedures such as packing of the laceration with omentum, hepatectomy or direct control of bleeding vessels within the liver substance by means of the Pringle maneuver, selective hepatic artery ligation, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were selected and combined based on the specific injury. In the 259 patients treated operatively, the survival rate was 86.9% (225/259); and 15 of 40 with retrohepatic venous injury (RHVI) were cured with the maximum blood transfusion of 60 units. In 42 patients treated by perihepatic packing, the bleeding was stopped in 20 of 25 (80%) with RHVI and in 14 of 17 (82%) without such injury ( p > 0.75). The percentage of failure of nonoperative management was 17.2% (17/99); and it was 46.7% (14/30) in patients with grade III-V injury. Death occurred in 3 (50%) of 6 failures of grade IV-V injury. The overall mortality rate was 11.8% (41/348), and 51% of the deaths were due to exsanguination. The results suggest that severe hepatic injuries, especially grade IV-V injuries, usually require surgical intervention; reasonable surgical procedures based on classification of liver trauma and combined application of techniques can increase the survival rate; and perihepatic packing is effective in dealing with RHVI.

A 26-year-old man who sustained multiple trauma and had renal failure secondary to rhabdomyolysis as the result of a motor vehicle accident presented with fever and blood cultures positive for Staphylococcus aureus. Bone and gallium scintigraphy were performed to evaluate sites of skeletal fracture for osteomyelitis. Identified was a focus of soft tissue infection related to the placement of a Gortex® dialysls shunt in the left groin. A Tc-99m RBC blood pool venogram demonstrated a filling defect in the left saphenous vein proximal to the shunt with soH tissue inflammation seen on MRI. An abscess was found at surgery for removal of the shunt

In an attempt to elucidate the mechanism by which excessive fluoride damages the central nervous system, the effects of exposure of PC12 cells to different concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs) were characterized here. Significant reductions in the number of binding sites for both [3H]epibatidine and [125I]alpha-bungarotoxin, as well as a significant decrease in the B(max) value for the high-affinity of epibatidine binding site were observed in PC12 cells subjected to high levels of fluoride. On the protein level, the alpha 3 and alpha 7 subunits of nAChRs were also significantly decreased in the cells exposed to high concentrations of fluoride. In contrast, such exposure had no significant effect on the level of the beta 2 subunit. These findings suggest that selective decreases in the number of nAChRs may play an important role in the mechanism(s) by which fluoride causes dysfunction of the central nervous system.

In order to investigate the molecular mechanism(s) underlying brain dysfunction caused by chronic fluorosis, neuronal nicotinic acetylcholine receptors (nAChRs) in the brain of rats receiving either 30 or 100 ppm fluoride in their drinking water for 7 months were analyzed in the present study employing ligand binding and Western blotting. There was a significant reduction in the number of [3H]epibatidine binding sites in the brain of rats exposed 100 ppm of fluoride, but no alteration after exposed to 30 ppm. On the other hand, the number of [125I]alpha-BTX binding sites was significantly decreased in the brains of rats exposed to both levels of fluoride. Western blotting revealed that the level of the nAChR alpha4 subunit protein in the brains of rats was significantly lowered by exposure to 100 ppm, but not 30 ppm fluoride; whereas the expression of the alpha7 subunit protein was significantly decreased by both levels of exposure. In contrast, there was no significant change in the level of the beta2 subunit protein in the brains of rats administered fluoride. Since nAChRs play major roles in cognitive processes such as learning and memory, the decrease in the number of nAChRs caused by fluoride toxicity may be an important factor in the mechanism of brain dysfunction in the disorder.

An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.

The aim of this study was to evaluate nitrate tolerance in patients with coronary heart diseases by vascular ultrasonography and treadmill exercise. According to the dosage interval of isosorbide dinitrate, 66 patients with coronary heart disease were divided into group A and group B in a random, control and double-blind method. Isosorbide dinitrate was given every 6 hours in group A and every 12 hours in group B for one week. Before and after the therapeutic period, the diameters of brachial arteries were measured by vascular ultrasonography at baseline and 5 min after sublingual administration of 10 mg isosorbide dinitrate, and the treadmill exercise test was performed in all subjects. The results showed that diameters of brachial arteries were increased significantly after sublingual isosorbide dinitrate in both groups before the therapeutic period. After the therapeutic period, dilation of brachial arteries induced by sublingual isosorbide dinitrate was more marked in group B than in group A. Compared with those before the therapeutic period, sigmaST segment depression decreased and treadmill walking time increased significantly in group B but not in group A after the therapeutic period. These findings suggest that less frequent doses of isosorbide dinitrate may prevent development of nitrate tolerance, which is confirmed by vascular ultrasonography combined with treadmill exercise in patients with coronary heart disease.

To evaluate the clinical significance of QT dispersion after exercise in patients with previous myocardial infarction, QT dispersion (QTd) and corrected QTd (QTcd) were assessed with standard 12 leads electrocardiogram in 90 patients with previous myocardial infarction and 30 healthy persons before and 3 min after a treadmill exercise test. In addition, 24 h ambulatory electrocardiogram and echo-cardiography were examined in all the subjects studied. Patients were followed up for 37.25 +/- 10.71 months. The results showed that there were no significant differences in the QTd and QTcd between the patients and the controls before exercise (36.11 +/- 13.42 ms versus 34.81 +/- 12.32 ms, P0.05, 41.22 +/- 13.49 as versus 39.91 +/- 13.56 ms, P0.05). Compared with those before exercise, QTd and QTcd were significantly increased in the patients 3 min after the exercise test (36.11 +/- 13.42 ms versus 47.20 +/- 14.41 ms, P0.01, 41.22 +/- 13.49 ms versus 59.57 +/- 18.90 ms, P0.01), but not in the controls (34.81 +/- 12.32 ms versus 38.76 +/- 12.09 ms, P0.05, 39.91 +/- 13.56 ms versus 43.27 +/- 17.77 ms, P0.05). The incidences of abnormal contraction of the left ventricular wall, aneurysms, NYHA III class,III class of Lown's ventricular arrhythmia classification and cardiac sudden death were significantly higher in group A with QTcd50 ms than that of group B with QTcd50 ms (P0.01). These findings indicate that the increased QT dispersion after exercise in 12 standard leads electrocardiogram might be associated with high incidences of sudden cardiac death and ventricular arrhythmia in the patients with previous myocardial infarction.

Transiently catecholaminergic cells (TC-cells) expressing tyrosine hydroxylase (TH) have been shown in a variety of tissues during embryonic life. To investigate the possible relationship of nitric oxide synthase (NOS)-containing renal neuronal somata (RNS) and the TC-cells, we examined serial 100 microm slices of whole kidneys for TH-immunofluorescence and NADPH-d histochemistry during prenatal and postnatal development. The number of TH-cells increased during the prenatal period, peaked at birth and were very rare by PD21. A subpopulation of TH-immunoreactive RNS displayed NADPH-d activity. By PD21 the TH-positive RNS had practically disappeared while the number of NADPH-d positive RNS was markedly increased. These results suggest that kidneys possess transient catecholaminergic cells which display NOS-activity and that NOS expression may be the end-point in the differentiation of the RNS.

An investigation of the changes in size, number and distribution of NOS-containing neuronal somata in the rat kidney was undertaken. The immunoperoxidase method for the staining of NOS and the histochemical method for the demonstration of NADPH-d were applied to serial thick sections (100 μm) of whole kidneys. Animals at embryonic day 14 (ED14), ED16, ED18, ED20, at birth (PD0), and at postnatal days 4 (PD4), PD12, PD21 and PD35 were studied. NOS-containing neuronal somata were observed by the 20th day of gestation in some kidneys and were consistently seen at birth. They were usually seen in groups of separated neuronal somata or in tight clusters. The neuronal somata were often attached or embedded in nerve bundles. As the kidney developed, the number of neuronal somata separated from each other increased, while the number of clusters remained relatively constant. The size of the neuronal somata increased with development. There were highly significant statistical differences in the size of the neuronal somata between all groups, except between PD12 and PD21. The distribution of neuronal somata at birth was similar to that of the adult. They could be found, (a) at the free renal pelvic wall; (b) in the connective tissue at the angular space between the renal pelvis and the renal parenchyma (SPP); and (c) along the interlobar vessels. At birth and in the early stages of development, the greatest number of neuronal somata were located at the renal pelvis. In the later stages of development, more neuronal somata appear in the connective tissue between the renal pelvis and the renal parenchyma. The location of NOS-containing neuronal somata suggests that they might have a modulatory role on the sympathetic and sensory renal nerves all through development.

Neuronal somata in the rat kidney are very often part of ganglionated plexus and contain nitric oxide synthase (NOS). Examining serial 100 μm slices of whole kidneys, we identified three subpopulations of neuronal somata by: (a) staining for NADPH-diaphorase (NADPH-d) histochernistry followed by the demonstration of dopamine β-hydroxylase (DBH) by immunoperoxidase, and (b) staining for DBH by immunofluorescence followed by the demonstration of NADPH-d histochemical activity. The largest subpopulation of neuronal somata displayed both DBH immunoreactivify and NADPH-d histochemical activity. The second largest group of somata showed NADPH-d activity only. A small group of neuronal somata showed only DBH immunoreactivity. The presence of catecholaminergic characteristics in NOS-containing neuronal somata is unusual and raises the question as to their origin. Their heterogeneity suggests different functions for the different subpopulations.