Objective To compare the dosimetry between inversely optimised intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy using the field-in-field technique (FIF) for whole-breast radiotherapy with a boost to the tumor bed after breast-conserving surgery.Methods IMRT and FIF treatment plans were respectively performed and optimised for 9 patients with early stage leftbreast cancer after breast-concerving surgery.The prescribed dose of breast was 50.4 Gy in 28 fractions,1.8 Gy per fraction and that of tumor bed was 61.6 Gy in 28 fractions,2.2 Gy per fraction.The conformity index,the dose and volume for OAR( organs at risks),time of planning and treatment for the two plans were compared.Results The conformity index(CI) for IMRT was improved compared with the FIF in breast [(1.82±0.16) vs.(2.21±0.15)] and tumor bed [(1.19±0.04) vs.(1.59±0.11),t=2.08,3.97,P ＜ 0.05 ].There was no difference for V20 of ipsilateral lung and V30 of heart between two plans.The Dmax and Dmean of the contralateral lung of FIF were (5.41 ±2.76) and (0.51 ±0.10) Gy,lower than those of IMRT [ (25.72 ± 2.61 ) and (7.46 ± 0.39) Gy,t =-22.44,- 21.14,P ＜ 0.05 ].The Dmax and Dmean of the contralateral breast of FIF were (8.50 ± 5.61 ) and (0.47 ± 0.11 ) Gy,lower than those of IMRT [(27.73±4.30) and (6.38±0.48) Gy,t=-5.66,-14.83,P＜0.05].ForFIF,theV5of the contralateral lung and breast were (0.09 ± 0.09) ％ and (0.45 ± 0.45 ) ％,respectively,lower than those of IMRT,which were (84.66 ±3.06) ％ and (60.79 ±4.94)％ (t =-28.19,- 12.80,P＜0.05).The time of optimised plan was (61.57 ± 0.89) min for FIF and(241.28 ± 1.06) min for IMRT (t=-32.35,P＜0.05),and that of treatment were (16.14±1.42) min for FIF and (29.85 ±0.59) min for IMRT (t =- 8.82,P ＜ 0.05).Conclusions For patients with early stage breast cancer after breast-concerving surgery,IMRT could improve the conformity index of target but increase the dose of eontralateral lung and breast.However,FIF has advantage on the time of optimising plan and treatment.

Objective To investigate the myocardial protection of intraoperative continuous in-fusion of esmolol in elderly patients undergoing laparoscopic surgery.Methods Sixty patients,thirty-two males and twenty-eight females,aged 65-80 years,weighing 40-80 kg,ASA physical status Ⅰ orⅡ,undergoing selective general anesthesia laparoscopic resection of gastrointestinal cancer were ran-domly divided into 2 groups (n = 30 ):esmolol group (group E)and control group (group NS). Group E was administered esmolol 0.3 mg/kg 3 minutes before intubation,then with a continuously infusing rate of 50 μg · kg-1 · min-1 until extubation.Group NS was administered saline instead. MAP,HR,SpO 2 ,PET CO 2 ,BIS and RPP were recorded before intubation (T0 ),intubation (T1 ), pneumoperitoneum (T2 ),the end of surgery (T3 ),extubation (T4 )and 30 minutes after extubation (T5 ).The serum levels of cTnI,CK,CK-MB and LDH were measured before anesthesia and 6,30 hours after surgery.Adverse cardiovascular event happened during perioperation and 3 months follow-ing up was recorded.Results HR,MAP,RPP at T1 ,T2 ,T4 in group E were obviously lower com-pared with group NS (P <0.05).There were no significant differences in the serum levels of cTnI, CK,CK-MB and LDH between two groups at different time points.No major adverse cardiovascular event happened in two groups during perioperation and 3 months following up.Conclusion Intraoper-ative continuous infusion of esmolol 50 μg· kg-1 · min-1 can not significantly influence the serum level of myocardial injury marker in the elderly patients without myocardial damage undergoing lapa-roscopic resection of gastrointestinal cancer.Howerver,it can effectively reduce the cardiovascular re-sponse caused by stimulation,decrease myocardial oxygen consumption,protect myocardial.

Objective To investigate the difference of apparent diffusion coefficients (ADCs) changes in three major salivary glands after gustatory stimulation using two different stimuli. Methods Thirty healthy volunteers were examined with a 1.5 T MR unit. A diffusion-weighted MR imaging (MR DWI) sequence was performed once at rest and continuously repeated 13 times after gustatory stimulation using a commercially available lemon juice and vitamin C tablets in the same volunteer by using self-controlled method. The subsequence of two stimuli was random. In addition, the salivary flow rates at rest and after stimulation were measured. Characteristics and differences in ADCs curves of three salivary glands before and after stimulation between two stimuli were analyzed. Comparison of maximum ADCs, maximum ADCs increase rates (IRs) and times to maximum ADCs(Tmax) between two stimuli was performed by using independent-samples t test. Correlation analysis between rest salivary flow rates and rest ADCs, the maximum salivary flow rates and ADCs after stimulation, the maximum salivary flow IRs and ADC IRs after stimulation were performed by using Pearson correlation test. Results In lemon juice stimulation group, the mean ADCs mostly showed a steady increase to peak values during the first DW MRI scan after stimulation in all glands, followed by a gradually decrease fluctuating slightly around the baseline values. In vitamin C stimulation group, the mean ADCs were significantly increased in all glands during the first DW MRI scan after stimulation, followed by a gradual upward trend till peak values. In lemon juice stimulation group, the mean Tmax of submandibular and sublingual glands[(184±122)s, (345±232)s, respectively] were significantly earlier than those[(454 ± 301)s, (528 ± 297)s, respectively] in vitamin C stimulation group (t=-3.517 and-2.548 respectively, P<0.01 for all). The mean maximum ADCs of three glands in lemon juice stimulation group[(1.05 ± 0.12) × 10-3 mm2/s, (1.22 ± 0.10) × 10-3 mm2/s and (1.26 ± 0.21) × 10-3 mm2/s, respectively] were all lower than those in vitamin C stimulation group[(1.13±0.13) ×10-3 mm2/s, (1.32±0.25) × 10-3 mm2/s and (1.57 ± 0.36) × 10-3 mm2/s, respectively], and the differences in parotid and sublingual glands between two groups were significant(t=-2.894 and-3.681 respectively, P<0.01 for all). The mean maximum ADC IRs of three glands in lemon juice stimulation group[(11.35±4.07)%, (8.81±5.40)%, (34.08±21.66)%, respectively] were significantly lower than those[(17.80 ± 12.72)%, (18.16 ± 18.93)%, (67.49 ± 46.04)% , respectively] in vitamin C stimulation group (t=-2.252,-2.330 and-3.432 respectively, P<0.05 for all) . In two groups, the mean maximum ADC IRs of parotid and submandibular gland were all significantly lower than sublingual gland (t=-5.994 and-6.443 respectively, P<0.01 for all). No correlation was observed between ADCs and salivary flow rates, ADC IRs and salivary flow rate IRs in two groups (P>0.05). Conclusion MR DWI with transient stimulation using lemon juice is more stable for evaluating the physiologic changes of salivary glands in vivo.

Objective: To analyze the clinical characteristics of streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes (S. pyogenes) in the third trimester to improve clinical awareness of this disease. Methods: A retrospective study was conducted to analyze the clinical data of two patients with STSS caused by S. pyogenes in Jinan Maternal and Child Health Care Hospital and nine reported cases of healthy pregnant women infected with S. pyogenes at 28-42 gestational weeks with detailed data retrieved from Chinese National Knowledge Infrastructure and PubMed database from January 1997 to December 2018. Results: The two cases admitted to our hospital were both multiparas, with onset in winter and no specific symptoms in early stage. Disseminated intravascular coagulation (DIC) was developed in both cases on admission. In one case, the fetal heart rate was reduced and disappeared soon after admission. The other patient was diagnosed as stillbirth on admission. Both patients died and blood culture revealed infection of group A streptococcus. Nine previous cases were reported in one Chinese and five English articles. No high-risk pregnancy or premature rupture of membranes was reported in these 11 cases. Among the 11 cases, ten were positive for S. pyogenes indicated by blood or tissue culture and one was positive for streptococcal toxin. Ten cases had high fever and three presented with respiratory symptoms in early stage. Abdominal pain and watery diarrhea were common symptoms and all patients developed multiple organ dysfunction and DIC. Cases occurred in winter or spring were more common. Nine women died within 36 h after the onset of fulminant symptoms. Only two survived and hospitalized for 90 d and 25 d, respectively, after emergent cesarean section indicated by reduced fetal heart rate. Unfortunately, both neonates died after birth. For the babies, there were seven intrauterine fetal deaths, one stillbirth and three live births, but only one survived (whose mother developed respiratory cardiac arrest 90 min after delivery). Conclusions STSS caused by S. pyogenes in pregnant women exacerbates rapidly with a high mortality. Early identification of clinical manifestations and rapid progress of the disease are crucial for early diagnosis and treatment, which may help improve maternal and fetal outcomes.

OBJECTIVE: To explore appropriate treatment modality of microinvasive cervical cancer (MIC) and to analyze prognosis and risk factors of recurrence. METHODS: A cohort of 324 Chinese patients with MIC diagnosed and treated at Peking Union Medical College Hospital was retrospectively reviewed. Demographic features, treatment modalities, pathologic parameters, risk factors of residual disease, survival and risk factors of recurrence were analyzed. RESULTS: Of all patients, 280 cases were staged IA1 and 44 cases staged IA2 MIC. Twenty-five cases (7.7%) were found to have lympho-vascular space involvement (LVSI), but no parametrial involvement or ovarian metastasis was detected. Only one staged IA2 patient with LVSI was found to have lymph node metastasis. 32.4% patients (82/253) had residual diseases after conization. No significant difference of LVSI, lymph node metastasis and residual disease after coniztion was found between stage IA1 and IA2 MIC patients. Multivariate logistic analysis showed positive margin was the only independent risk factor of residual disease after conization (odds ratio [OR], 4.18; p<0.001). Recurrence occurred in five cases, but no mortality was found. Progression-free survival for stage IA1 patients treated by conization or hysterectomy was similar (92.3% and 98.8%, p=0.07). Cox regression analysis revealed LVSI as an independent risk factor for recurrence in stage IA1 patients (OR, 12.14; p=0.01). CONCLUSION: For stage IA1 patients with negative resection margin and no LVSI, conization can be an ideal treatment modality. For stage IA2 patients, more conservative surgery such as simple hysterectomy may be considered. LVSI is an independent risk factor for recurrence in patients with stage IA1 cervical cancer.
Adult ; Aged ; Cohort Studies ; Conization/methods ; Female ; Humans ; Hysterectomy ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Uterine Cervical Neoplasms/pathology/*surgery ; Young Adult

OBJECTIVE:To study the protective effect of fingolimod on renal ischemia reperfusion injury (RIRI) model mice and its mechanism.METHODS:A total of 60 mice were randomly divided into sham operation group,model group,fingolimod group (1 mg/kg) and fingolimod+wortmannin group [fingolimod 1 mg/kg+phosphatidylinositol 3-kinase (PI3K) specific blocker wortmarmin 1.4 mg/kg],with 15 mice in each group.Except for sham operation group,RIRI model was induced in other 3 groups,and those model mice were given relevant medicine via caudal vein at once 24 h before surgery.Serum of mice were collected in each group after 24 h perfusion.Serum levels of Scr and BUN were measured by automatic biochemical analyzer.The pathological changes of renal tissue were observed under light microscope.The protein expression of intercellular cell adhesion molecule-1 (ICAM-1),monocyte chemoattractant protein-1 (MCP-1) and phosphorylated protein kinase B (p-Akt) in renal tissue were measured by Western blot assay.RESULTS:Compared with sham operation group,the serum levels of Scr and BUN in model group were increased significantly (P＜0.01).Pathological changes were found in the kidney,and RIRI led to widespread renal tubular epithelial cell injury,apoptosis and inflammatory cells infiltration.The protein expression of ICAM-1 and MCP-1 in renal tissue were increased significantly (P＜0.01),the protein expression of p-Akt was increased slightly (P＞0.05).Compared with model group,other indexes of fingolimod group were improved significantly (P＜0.01) except that the protein expression of p-Akt in renal tissue was increased significantly (P＜0.01).Compared with fingolimod group,above indexes of fingolimod+wortmannin group were reversed (P＜0.05 or P＜0.01).CONCLUSIONS:Fingolimod can obviously ameliorate renal injury induced by RIRI in mice,the mechanism of which may be associated with the activation of PI3K/Akt signaling pathway.

Objective: To evaluate the precision of image registration between MRI simulation (MRIsim) and CT simulation compared to diagnostic MRI(MRIdiag) and to provide information for further application of MRIsim. Methods: A total of 24 patients who underwent both MRIsim and MRIdiag were enrolled, including 8 patients with gliomas, 8 with nasopharyngeal carcinomas and 8 with prostate cancers. MRIsim and MRIdiag images of each patient were fused with CT. The OARs were delineated on three modalities of images and targets were delineated on fusion image of MRIsim with CT (F_CTMsim) and fusion image of MRIdiag with CT (F_CTMdiag) respectively. The concordance index (CI), Dice′s similarity coefficient (DSC) between the OARs and image similarity index (S) based on images from MRIsim, MRIdiag and CT were evaluated. IMRT plans were designed based targets on F_CTMsim and OARs on CT images, and differences in dosimetry of targets and OARs were evaluated subsequently. Results: Volumes of most OAR from three modalities of images showed no statistically significant difference(P>0.05). All the CI and DSC between the OARs derived from MRIsim and CT were higher than those corresponding values from MRIdiag, and a statistically significant difference was achieved in 50% of these OARs (t=2.58-5.47, P<0.05). The S values of MRIsim and MRIdiag compared with CT were 0.89 and 0.83 respectively (t=5.77, P<0.05). MRIsim improved the S value by 10% (2%-56%) compared with MRIdiag. No further differences in dosimetry were found on all OARs and all targets(P>0.05). Conclusions The precision of image registration can be significantly improved by introducing MRIsim into radiotherapy planning design compared with MRIdiag. However, no significant differences in dosimetry were found on targets produced by rigid registration and manual adjustment method .

Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

OBJECTIVE To investigate the effects of osthole （OST） on renal interstitial fibrosis in diabetic nephropathy （DN） model mice. METHODS The diabetic mice model was established by the tail vein injection of streptozotocin once， and the DN model was established by feeding for 12 weeks after successful modeling of diabetes. Diabetic model mice were randomly divided into model group， low-dose， moderate-dose， high-dose groups （20， 40， 80 mg/kg） of OST， with 10 mice in each group. After successful modeling of diabetes， the mice were given corresponding drugs or solvent （model group） intragastrically， once a day， for consecutive 12 weeks， and the normal control group was set up at the same time. After the last administration， the levels of fasting blood glucose， 24 h urinary protein， serum creatinine （Scr） and blood urea nitrogen were tested in each group. Masson staining was used to observe the deposition of collagen fibers in renal interstitium； the expressions of E-cadherin and vimentin in renal cortex were detected by immunohistochemical staining. The protein expressions of follistatin-like protein 1 （Fstl1） and Snail family transcriptional repressor 1 （Snail1）， the phosphorylation of protein kinase B （Akt） （calculated by p-Akt/Akt） in the renal cortex were detected by Western blot. RESULTS Compared with normal control group， the levels of fasting blood glucose， 24 h urinary protein， Scr and blood urea nitrogen， collagen fiber deposition ratio of renal interstitium， the expression of vimentin， protein expressions of Fstl1 and Snail1， p-Akt/Akt in renal cortex were increased significantly （P＜0.01）， as well as the expression of E-cadherin was decreased significantly （P＜0.01）. Compared with model group， above indexes of OST groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Preventive use of OST can effectively reduce fasting blood glucose level， protect renal function and inhibit epithelial-mesenchymal transition of DN model mice， and delay the progression of renal interstitial fibrosis ， the mechanism of which may be associated with the suppression of Fstl1/Akt/Snail1 signaling pathway.

Objective:To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up.Methods:Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups.Results:Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio ( HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO ( P<0.05). Conclusion:Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases.