Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective:To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer.Methods:Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM).Results:In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant ( P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively ( P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% ( P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% ( P>0.05), local recurring free survival rates were 100% and 92.3% ( P>0.05), distant metastasis free survival rate were 75.6% and 77.3% ( P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival ( P<0.05). Conclusion:In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

Objective:To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer.Methods:Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM).Results:In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant ( P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively ( P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% ( P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% ( P>0.05), local recurring free survival rates were 100% and 92.3% ( P>0.05), distant metastasis free survival rate were 75.6% and 77.3% ( P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival ( P<0.05). Conclusion:In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

Objective:To evaluate the clinical efficacy of radiotherapy in the treatment of extracranial metastatic breast cancer, and to investigate the significance and prognostic factors of whole-lesion radiotherapy (WLRT).Methods:Clinical data of 85 patients with extracranial metastatic breast cancer treated with radiotherapy between 2014 and 2019 were retrospectively analyzed. Thirty-six patients were assigned into the WLRT group and 49 in the non-WLRT group. The local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan- Meier method, log-rank test and univariate prognostic analysis. Cox proportional hazards model was used for multivariate prognostic analysis. Results:The median follow-up time was 26.7 months. The 2-year LC, PFS, OS rates were 77%, 26%, 77%, respectively. The 2-year LC (91% vs. 67%, P=0.001), PFS (47% vs. 8%, P<0.001), OS rates (84% vs. 71%, P=0.010) in the WLRT group were significantly higher than those in the non-WLRT group, respectively. Multivariate analysis demonstrated that WLRT was an independent favorable prognostic factor for the LC, PFS and OS. Furthermore, bone metastasis alone was associated with improved LC and positive hormone receptor status was correlated with improved OS. Conclusions:WLRT has the potential to prolong the survival of patients with extracranial metastatic breast cancer. The patients with bone metastases alone obtain better LC, whereas those with negative hormone receptor status has worse OS.

Objective:To investigate the relationship between gastric filling status and intra-or inter-fractional tumor displacement in patients with adenocarcinoma of the esophagogastric junction (AEG) undergoing preoperative radiotherapy.Methods:From October 2018 to June 2019, 10 patients with locally advanced AEG who received totally neoadjuvant therapy were enrolled in this prospective study. Patients received two markers implanted at the cranial and caudal borders of the tumors under gastroscope and a total of 20 fiducial markers were implanted finally. All patients underwent 4DCT scan under the gastric fasting and filling status. Ten images of 0% to 90% respiratory phase were automatically reconstructed by the system (Pinnacle 3, version 9.1, Philips Medical Systems, Eindhoven, The Netherland). Each patient obtained one hundred sets of images. Results:In the tumors proximal to the chest, gastric filling did not significantly affect intrafractional or interfractional tumor displacements. Nevertheless, in the tumors distal to the chest, the interfractional displacement in the cranio-caudal (CC) direction under the gastric fasting status was significantly larger compared with that under the gastric filling status (6.22±4.67 mm vs. 4.13±3.68 mm, P=0.013). To ensure 95% of the prescribed dose irradiated to at least 90% of the tumor volume during the radiotherapy, the margins of tumors proximal to the chest in the left-right (LR), antero-posterior (AP) and CC directions were 9 mm, 8.5 mm, 12.1 mm under gastric filling status with 300 ml semi-fluid. Six patients diagnosed with gastric cancer with proximal thoracic fiducial markers treated by preoperative radiotherapy were included in the validation group, revealing that the fiducial markers of 93% patients were covered in this margin. Conclusion:During the preoperative radiotherapy in AEG patient, the approach of quantitative gastric filling can be considered.

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Objective:To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) model of" neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy (CNCT) followed by surgery" for locally advanced gastric cancer.Methods:From 2018 to 2020, 28 patients clinically diagnosed with locally advanced gastric adenocarcinoma or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer were prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45 Gy, 1.8 Gy/f. Concurrent chemotherapy was S-1 at a dose of 40-60 mg twice daily. Then, patients received four to six cycles of CNCT of SOX regimen at three weeks after neoadjuvant chemoradiotherapy. D 2 lymphadenectomy was performed at 4-6 weeks after CNCT. Results:A total of 28 patients completed the whole therapy. Grade 3 or above adverse events occurred in 3 cases (11%) during CCRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7%) developed leukopenia and 3 cases (11%) of thrombocytopenia during CNCT. Twenty patients (71%) completed the surgery. The proportion of patients with pathological complete remission (pCR) was 50%. Three patients experienced surgical complications including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. All were recovered after symptomatic treatment.Conclusion:Interim analysis results demonstrate that TNT can yield significant down-staging for patients with locally advanced gastric cancer, which causes tolerable adverse events and postoperative complications.