Volume 122  ·  Issue 04  ·  2009

In the 21st century medicine is characterized by population problem, the great impact of computer and information technology, the contribution of genetics development to disease prevention and treatment, and the reform of health care system. By 2025, there will be 274 million people over 60 years old and cancer may be the primary killer as well in China. The incidences of cancers of the lung, intestine, and breast are on the rise; the incidence of cervical cancer is decreasing in developed countries while increasing in developing ones。

Abstract：Background Conization is being widely accepted for diagnosis and treatment of cervical intraepithelial neoplasia (CIN). There is controversy as to which factors are most predictive of a positive cone margin and the clinical significance of it. We conducted this study to identify the predictive factors and to evaluate the clinical significance of a positive cone margin in CIN Ⅲ patients.Methods A retrospective review was conducted of 207 patients who had undergone conization due to CIN Ⅲ from January 2003 to December 2005 at Peking Union Medical College Hospital. Of these, 67 had a subsequent hysterectomy. Univariate and multivariate analysis were utilized to define the predictive factors for a positive cone margin, and to compare the pathologic results of conization with subsequent hysterectomy.Results One hundred and fifty-one (72.9%) were margin free of CIN Ⅰ or worse, 37 (17.9%) had CIN lesions close to the margin and 19 (9.2%) had margin involvement. A total of 56 cases (27.1%) had positive cone margins (defined as the presence of CIN at or close to the edge of a cone specimen). Univariate analysis showed that the parity, cytological grade, multi-quadrants of CIN Ⅲ by punch biopsy, gland involvement, as well as the depth of conization were significant factors correlated with a positive cone margin (P<0.05). However the age, gravidity, grade of dysplasia in punch biopsy, as well as the cone methods were not significantly correlated (P >0.05). Multivariate analysis revealed that the cytological grade (OR=1.92), depth of conization (OR=2.03), parity (OR=3.02) and multi-quadrants of CIN Ⅲ (OR=4.60) were significant predictors with increased risk for positive margin. The frequency of residual CIN Ⅰ or worse in hysterectomy specimens was found to be 55.6% (20/36) in patients who were margin free, 71.4% (15/21) in patients with CIN occurring close to margin, and 80.0% (8/10) in patients with margin involvement. The frequency of residual CIN Ⅲ or worse was found to be 13.9% (5/36), 23.8% (5/21) and 50.0% (5/10) respectively in different groups.Conclusions Cytological grade, depth of conization, parity and multi-quadrants of CIN Ⅲ in punch biopsy were significant factors with increased risk in predicting a positive cone margin. Margin status of conization did not mean the presence or absence of CIN, but rather the varied frequency of residual CIN in specimens of subsequent hysterectomy. In view of this fact, it is suggested that the margin status of conization be a valuable surrogate marker for clinical management of CIN Ⅲ。

Abstract：Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the leading causes of sudden cardiac death. Recent studies have shown that ARVC, which is an inheritable genetic change, results from mutations in genes encoding desmosomal proteins. Plakophilin-2 is an important component of the desmosome. Because the full range of genetic variations related to ARVC is unknown and no related studies of the Chinese population have been reported, we aimed to investigate the genetic variation of plakophilin-2 in ARVC patients from the Southern Region of China.Methods Genomic DNA was isolated from peripheral blood samples of all 34 ARVC patients, who were screened through a clinical evaluation. They were used to detect variations in the sequences of the plakophilin-2 genes by polymerase chain reaction amplification in combination with direct sequencing.Results In exon-1 of the plakophilin-2 gene, a deletion mutation (c.145_148 del GACA) was found in one family pedigree. The mutation was also found in exon-2, 4, and 11 of the plakophilin-2 gene. The QT interval dispersion of the ECG was considerably longer in the mutation group than in the non-mutation group of ARVC patients, and this result was statistically significant (P <0.05).Conclusion We discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese ARVC population。

Abstract：Background Endometriosis is a common gynecological disease. This study aimed to screen proteins that were expressed differently in patients with endometriosis versus normal controls using proteomic techniques, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).Methods Protein chip SELDI-TOF-MS combines the advantages of microarray and mass spectrometry, and can screen latent markers in sera of patients with endometriosis. Serum samples from patients and normal volunteers were analyzed by SELDI-TOF-MS.Results After comparing the serum protein spectra of 36 patients with 24 normal controls, 24 differently expressed potential biomarkers (P <0.01) were identified. Using Biomarker Pattern software, we established a tree model of the 60 serum protein spectra. When using the three biomarkers to classify the samples, the sensitivity for diagnosing endometriosis was 91.7%, specificity was 95.8%, and coincidence rate was 93.3%. Then we used serum samples from 12 patients and 8 normal controls to validate the tree model and report the sensitivity for diagnosing endometriosis was 91.7%, specificity was 75%, and coincidence rate was 85%.Conclusions SELDI-TOF-MS may be a useful tool in high-risk population screening for endometriosis. The identification and application of the biomarkers need to further study。

Abstract：Background Hysterectomy is a very common surgery in gynecology. Ideal surgery for hysterectomy is microinvasive with few complications. There are three major routes of hysterectomy that are currently used. The aim of this study was to identify the differences of peri-operative outcome among the patients who underwent the three different approaches.Methods One hundred and one women undergoing hysterectomy for myoma had the procedure performed by laparoscopic assisted vaginal hysterectomy (LAVH), total vaginal hysterectomy (TVH) or total abdominal hysterectomy (TAH) in a randomized study. We compared the course of peri-operative and post-operative outcome for the three different approaches. Results were evaluated by linear regression analysis, Fishers exact test and Student's t test for independent samples.Results The operation time among the three procedures was not significantly different (P >0.05). The amount of blood loss in the TVH group was less than in the LAVH and TAH groups (P<0.05). The pain score 3 hours after operation in the LAVH group was significantly lower than in the TAH and TVH groups (P<0.001). The pain scores in the LAVH and TVH groups were lower than in the TAH group at 24 and 48 hours after operation (P<0.01). The women who underwent LAVH and TVH had a shorter hospitalization stay (P <0.001). The highest body temperature after operation in the TAH group was higher than that in LAVH and TVH groups (P <0.001).Conclusions LAVH and TVH are better procedures for women requiring hysterectomy. The peri-operative and post-operative courses of TVH are better than LAVH, excluding the pain score 3 hours after operation. Vaginal hysterectomy is the most cost-effective approach but the final choice for the route of hysterectomy can depend on many factors such as gynecological disease, patients' health status and experiences of the gynecologist。

Abstract：Background Estrogen deficiency causes atrophic changes within the urogenital tract, and is associated with urinary symptoms. The purpose of this study was to investigate the effects of estrogen and tibolone on bladder histology, and the changes of estrogen receptor α and β (ERα and β) protein expression in the detrusor muscle.Methods Forty female rats were separated into four groups of ten each. They received a sham operation (Sham), ovariectomy (Ovx), ovariectomy plus estrogen replacement (Ovx+E), or ovariectomy plus tibolone treatment (Ovx+T). After 12 weeks each rat was anesthetized and the bladders were removed. The bladders' ultra structure, collagen fiber (CF) to smooth muscle(SM) ratio and ER subtypes were studied. Statistical analyses were performed using the one-way analysis of variance test.Results Ovx resulted in significant degeneration in bladder ultra structure; however, estrogen and tibolone reversed those changes. Ovx increased the CF/SM ratio, estrogen and tibolone resulted in an increase. Two estrogen receptors (ERs) were expressed in the bladder detrusor, with ERβ the main subtype. Ovx resulted in up-regulation of ERα and down-regulation of ERβ. With estrogen and tibolone treatment, ERβ showed a significant increase but ERα showed no significant difference compared with Ovx.Conclusions Estrogen deficiency deteriorates bladder ultra structure and histology. Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased SM density. ERβ has an important role in mediating estrogen function in the bladder. Tibolone has a mild estrogenic action and has an effect on bladder function and structure to some degree。

Abstract：Background Small for gestational age (SGA) infants are associated with a high rate of oligohydramnios, stillbirth and cesarean delivery. Among SGA patients there is a higher risk of neonatal complications, such as polycythemia, hyperbilirubinemia, and hypothermia. Additionally, the SGA infant is prone to suffer from major neurologic sequelae, as well as cardiovascular system disease, in later life. Proper monitoring and therapy during pregnancy are, therefore, of utmost importance. The present study aimed to investigate the influential and prognostic factors of SGA infants.Methods From January 2001 to June 2007, a total of 55 SGA neonatal infants were included in a study group. All were born at Peking Union Medical College Hospital, with regular formal antenatal examinations. In addition, a total of 122 cases of appropriate for gestational age (AGA) infants were bom at the same time and were registered into a control group. All cases were singleton pregnancies with detailed information of the maternal age, gravidity, parity, maternal height and weight, complications, uterine height and abdominal circumference, results from transabdominal ultrasonography between 32-38 gestational weeks, pregnancy duration, delivery manner, placenta, umbilical cord, and neonatal complications.Results Significant differences were observed in placenta weight and neonatal malformations between the study and control groups. Multivariate analysis revealed increased parity, maternal hyperthyroidism and hyperthyroidism history as risk factors. Fetal abdominal circumferences less than 30 and 32 cm at 32-38 gestational weeks respectively, as determined by ultrasonography, resulted in a Youden index of 0.62.Conclusions SGA infants were associated with a greater risk of smaller placentas and infant malformations. Increased parity, maternal hyperthyroidism, and a hyperthyroid history were risk factors for SGA infants. Fetal abdominal circumference less than 30 cm at 32 gestational weeks and less than 32 cm at 38 weeks, as determined by ultrasonography, was considered an effective index for SGA。

Abstract：Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4+ T cells.Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/J×DBN2 (SA group, n=14), the normal pregnant mouse model CBA/J×BALB/c (NP group, n=13), and normal non-pregnant CBA/J mice (NNP group, n=11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4+ T cells was measured by double-label flow cytometry (FCM) method.Results In peripheral blood, the SA group had significantly lower CCR3 expression (P <0.01) and higher CCR5 and CXCR3 expression (P <0.01) on CD4+ T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference (P >0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P <0.01) and higher CCR5 and CXCR3 expression (P <0.05) on CD4+ T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression (P <0.01), but was not statistically different with regards to the other two chemokines (P >0.05). In thymus, the SA group had significantly lower CCR3 expression (P <0.05) and higher CXCR3 expression (P <0.05) on CD4+ T cells than the NP group, with no significant difference in CCR5 expression (P >0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P <0.01), but there was no statistical difference in CXCR3 and CCR5 expression (P >0.05) between the two groups.Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4+ T cells may play an important role in the pathogenesis of spontaneous abortion。

Abstract：Background Bifurcation angles may have an impact on the clinical outcomes of crush stenting. We sought to compare high (≥60(°)) with low (<60(°)) bifurcation angle in patients who underwent either classical or double kissing (DK) crush stenting for bifurcation lesions from the DKCRUSH-1 data base.Methods There were 212 patients with 220 lesions, some with low-angle (n=138) and some with high-angle (n=74). Angiography was indexed at 8-month after procedure. Primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and target lesion revascutarization (TLR). Secondary endpoint included late lumen loss, the rate of restenosis, and final kissing balloon inflation (FKBI).Results At 8 months, clinical follow-up was 100%; angiographic follow-up was 75% in the low-angle group and 83.3% in the high-angle group. There were no significant differences in the FKBI between the high-angle group (91.43%) and the low-angle group (82.39%). In the high angle group, there was a significant difference in contrast volume used (P=0.005) but no significant difference in acute gain, minimum lumen diameter (MLD), late loss and diameter stenosis in the pre-bifurcation segment, post-bifurcation segment or side branch. When lesions were assigned into with- (n=133) and without-FKBI (n=42), significant side-branch late loss was seen in the group without-FKBI ((0.65±0.49) mm vs (0.47±0.62) mm, P=0.02), with a resultant greater restenosis rate (37.68% vs 18.32%, P=0.001). No difference was detected in the MACE free survival rate between the high and low angle groups (82.39% vs 82.36%, P=0.84). The rate of stent thrombosis tended to be higher in the lower-angle group although there was no significant difference (P=0.38). The TLR free survival rate was 87.2% in the with-FKBI group vs 73.5% in the without-FKBI group (P=0.001). Cox regression analysis showed that the independent predictors for target vessel revascularization were the side branch stent MLD post stenting (hazard ratios (HR) 1.028, 95% Cl 2.357-16.233, P=0.002), lack of FKBI (HR 4.910, 95% CI 4.706-8.459, P=0.001) and unsatisfactory kissing (HR 3.120, 95% CI 2.975-5.431, P=0.001).Conclusions Bifurcation angles do not influence the clinical outcome of crush stenting. Successful final kissing balloon inflation, regardless of bifurcation angles, can predict TLR。

Abstract：Background There is few study to determine whether the use of the lightwand technique alone could achieve effective, safe and successful awake endotracheal intubation (ETI), therefore we designed a prospective clinical study to systematically evaluate the feasibility, safety and efficacy of awake ETI using the lightwand alone in patients with difficult airways.Methods Seventy adult patients with difficult airways were enrolled in this study. After the desired sedation with fentanyl and midazolam, airway topical anesthesia was performed with 9 ml of 2% lidocaine, which were in order sprayed in three aliquots at 5 minutes intervals into the supraglottic (two doses) and laryngotracheal areas (one dose) using a combined unit of the lightwand and MADgic atomizer. After airway topical anesthesia, awake ETI was performed using a Lightwand. Subjective assessments by patients and operators using the visual analogue scores (VAS), and objective assessments by an independent investigator using patients' tolerance and reaction scores, coughing severity, intubating conditions and cardiovascular variables were taken as the observed parameters.Results Of 210 airway sprays, 197 (93.8%) were successfully completed on the first attempt. The total time for airway spray was (14.6±1.5) minutes. During airway topical anesthesia, the average patients' tolerance scores were 1.7-2.3. After airway topical anesthesia, the mean VAS for discomfort levels that the patients reported was 6.5. Also airway topical anesthesia procedure was rated as acceptable and no discomfort by 94.3% of patients. The lightwand-guided awake ETI was successfully completed on first attempt within 29 seconds in all patients. During awake ETI, patients' reaction and coughing scores were 1.9 and 1.6, respectively. All patients exhibited excellent or acceptable intubating conditions. Cardiovascular monitoring revealed that changes of systolic blood pressure and heart rate at each stage of airway manipulations were less than 20% of baseline values. The postoperative follow-up showed that 95.7% of patients had no recall or slight memories of all airway instrumentation. The incidence of postoperative mild airway complications was 38.6%.Conclusion Alone use of the lightwand technique can achieve effective, safe and successful awake ETI in patients with difficult airways。

Abstract：Background Congenital heart disease (CHD) is the most common developmental anomaly in newborns. The germline mutations in GATA4 and NKX2.5 genes have been identified as responsible for CHD. The frequency of GATA4 and NKX2.5 mutations in Chinese Uygur patients with CHD and the correlation between their genotype and CHD phenotype are unknown.Methods We examined the coding region of GATA4 and NKX2.5 genes in 62 Chinese Uygur patients with CHD and 117 Chinese Uygur individuals as the controls by denaturing high performance liquid chromatography (DHPLC) and sequencing.Results Two heterozygous missense mutations of c.1220C>A and c.1273G>A in GATA4 gene, which cause the amino acid residue changes of P407Q and D425N in GATA4, were found in a patient with tetralogy of Fallot and a patient with ventricular septal defect, respectively. The two patients did not have atrioventricular conduct defects or non-cardiac abnormalities. The two mutations are expected to affect the protein function. There were no reported NKX2.5 mutations in the patients.Conclusion Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population。

Abstract：Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody (PRA) against human leukocyte antigen (HLA) is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients' PRA on two-year outcome in presensitized renal allograft recipients.Methods We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin (Ig) G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients (control group). HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers (PCR-SSP). We analyzed the factors influencing the early graft outcome (two-year rejection rates and survival rates of the grafts), including HLA mismatching, class and degree of panel reactivity, and target antigen of donors.Results Presensitized recipients had a worse two-year outcome than unsensitized recipients (P=0.019 for rejection rate, P=0.01 for survival rate). The difference in number of HLA-mismatched alleles with either 6-antigen matching (Ag M) standard or amino acid residue matching (Res M) standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-Ⅰ and PRA-Ⅱ antibodies had a significantly worse two-year outcome (P=0.001 for rejection rate, P=0.002 for survival rate). The two-year outcomes of the peak PRA ≥50% group and its subgroup, at-transplant PRA ≥50% group, were significantly worse compared with the control group (P=0.025 and P=0.001 for rejection rate, P=0.043 and P=0.024 for survival rate). The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-Ⅰ target antigen positive group, were significantly higher than the control group (P=0.001 and P=0.001), target antigen negative group (P=0.003 and P=0.001), and peak target antigen positive with negative at-transplant target antigen group (P=0.024 and P=0.002). Two-year graft survival rates of the target antigen positive group and HLA-Ⅰ target antigen positive group were significantly lower than the control group (P=0.012 and P=0.001). The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitizedrecipients with pre-transplant plasmapheresis or immunoadsorption (PRA prepared group) had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group (P=0.004 for rejection rate and P=0.005 for survival rate). Hyperacute rejection (HR) occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-Ⅱ (for an unknown target antigen). No HR occurred in eight cases with positive HLA-Ⅱ target antigens.Conclusions Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections。

Abstract：Background Cervicogenic headache (CEH) is caused by a structural abnormality in the cervical spine. Available treatments for CEH include medical therapy, local botulinum toxin injection, cervical epidural corticosteroid injection, and surgery. The objective of this study was to investigate the safety and efficacy of a continuous epidural block of the cervical vertebra.Methods Medical records were retrospectively analyzed for 37 patients diagnosed with CEH treated by a continuous epidural block of the cervical vertebra with lidocaine, dexamethasone, and saline (5 ml/min) for 3-4 weeks and triamcinolone acetonide 5 mg once weekly for 3-4 weeks. Pain was measured via the visual analogue scale (VAS) in combination with quality of life assessment. Outcome measures were patient-reported days with mild or moderate pain, occurrence of severe pain, and the daily oral dosages of non-steroidal anti-inflammatory drug use (NSAID).Results In the 3 months immediately preceding placement of the epidural catheter, the mean number of days with mild or moderate pain was 22.0±4.3. The mean occurrence of severe pain was (3.20±0.75) times and the mean oral dosage of NSAID was (1267±325) mg. During the first 6 months after epidural administration of lidocaine and corticosteroids, the mean number of days with mild or moderate pain, the mean occurrence of severe pain, and the mean daily oral dosages of NSAIDs were significantly decreased compared to 3-month period immediately preceding treatment (P <0.01). By 12 months post-treatment, no significant difference in these three outcome measures was noted.Conclusions Continuous epidural block of the cervical vertebra for patients with CEH is effective for at least six months. Further research is needed to elucidate mechanisms of action and to prolong this effect。

Abstract：Objective The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines and Committee for Proprietary Medicinal Products (CPMP) papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.Data sources The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point (1990) was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information (CNKI). ICH guidelines and CPMP papers were downloaded from their official websites. The keywords "clinical trial", "non-inferiority" and "non-inferiority margin" were used.Study selection Forty-three original articles and critical reviews, ICH E10 guideline and CPMP papers were selected.Results The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type Ⅰ error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western countries and China.Conclusions Besides the magnitude and variability of the standard control and placebo effects, the determination of the margin depends on other factors, such as, the safety profiles of the two comparative therapies, method of administration and product cost. Hence the margin should be made specifically for a certain case. Reference criteria for different medications should be given to avoid the arbitrary conclusion。

It has been well documented that bone morphogenetic proteins (BMPs), a group of proteins belonging to the transforming growth factor-β (TGFβ) superfamily, can induce bone formation, both in vivo and in vitro。

Leiomyomatosis peritonealis disseminata (LPD) is a rare but well-documented disorder mainlv found in young women。

Hypoxemia during one-lung ventilation (OLV) is normal。

To the Editor: We read the interesting recent article by Ding et al1 concerning the value of somatosensory evoked potentials (SEPs) in the diagnosis and prognosis of cervical spondylotic myelopathy, as well as the usefulness of monitoring intraoperative potentials in terms of safety and predictive factors。