Neuronal activities in the rostral ventromedial medulla associated with experimental occlusal interference-induced orofacial hyperalgesia.

The imbalanced conditions of pronociceptive ON-cells and antinociceptive OFF-cells in the rostral ventromedial medulla (RVM) alter nociceptive transmission and play an important role in the development of chronic pain. This study aimed to explore the neuroplastic mechanisms of the RVM ON-cells and OFF-cells in a male rat model of experimental occlusal interference (EOI)-induced nociceptive behavior reflecting orofacial hyperalgesia and in modified models involving EOI removal at early and later stages. We recorded the mechanical head withdrawal thresholds (HWTs), orofacial operant behaviors, and the activity of identified RVM ON-cells and OFF-cells in these rats. EOI-induced orofacial hyperalgesia could be relieved by EOI removal around postoperative day 3; this effect could be inhibited by intra-RVM microinjection of the kappa-opioid receptor agonist U-69593. EOI removal around postoperative day 8 did not relieve the orofacial hyperalgesia which could however be reversed by intra-RVM microinjection of the NK-1 receptor antagonist L-733060. The activity of ON-cells and OFF-cells did not change during both the initial 3 and 6 days of EOI. When EOI was removed on postoperative day 3, OFF-cell responses decreased, contributing to the reversal of hyperalgesia. When EOI lasted for 8 days or was removed on postoperative day 8, spontaneous activity and stimulus-evoked responses of ON-cell increased, contributing to the maintained hyperalgesia. In contrast, when the EOI lasted for 14 days, OFF-cell responses decreased, possibly participating in the maintenance of hyperalgesia with persistent EOI. Our results reveal that adaptive changes in the RVM were associated with orofacial pain following EOI placement and removal.SIGNIFICANCE STATEMENTA considerable proportion of patients suffered from chronic orofacial pain throughout life despite the therapies given or removal of potential etiological factors. However, current therapies lack effectiveness due to limited knowledge of the chronicity mechanisms. Using electrophysiological recording, combined with a behavioral test, we found that the prevailing descending facilitation in the rostral ventromedial medulla (RVM) participates in the maintenance of orofacial hyperalgesia following late removal of nociceptive stimuli, while the prevailing descending inhibition from the RVM may contribute to the reversal of orofacial hyperalgesia following early removal of nociceptive stimuli. Thus, variable clinical outcomes of orofacial pain may be associated with descending modulation and an optimal window of time may exist in the management of chronic orofacial pain.

Predictive value of DEEPVESSEL-fractional flow reserve and quantitative plaque analysis based on coronary CT angiography for major adverse cardiac events.

AIM: To investigate the predictive value of the combination of DEEPVESSEL-fractional flow reserve (DVFFR) and quantitative plaque analysis using coronary computed tomographic angiography (CCTA) for major adverse cardiac events (MACE). METHOD: In this retrospective study, data from 69 vessels from 58 consecutive patients were collected. These patients who underwent coronary angiography (CAG) with DVFFR were divided into MACE-positive and MACE-negative groups. DVFFR measurements were obtained from CCTA images acquired before CAG, and an FFR or DVFFR value ≤ 0.80 was considered haemodynamically significant. CCTA images were analysed quantitatively using automated software to obtain the following indices: total plaque volume (TPV) and burden (TPB), calcified plaque volume (CPV) and burden (CPB), non-calcified plaque volume (NCPV) and burden (NCPB), low-attenuation plaque (LAP), minimum lumen area (MLA), stenosis grade (SG) and lesion length (LL). Univariate and multivariate logistic regression, correlation, and receiver operating characteristic (ROC) analyses were used for statistical analysis. RESULTS: DVFFR was highly correlated with invasive FFR (R=0.728), and the Bland-Altman plot showed good agreement between DVFFR and FFR (95% CI: -0.109-0.087) on a per-vessel level. DVFFR showed a high diagnostic performance in identifying abnormal haemodynamic vessels, with an area under the ROC curve (AUC) of 0.984. In multivariate analysis, the following biomarkers were predictors of MACE: DVFFR ≤ 0.8, SG, TPB, NCPB, and LL values. The combination of the above independent risk factors yielded the most valuable prediction for MACE (AUC:0.888). CONCLUSIONS: DVFFR was highly correlated with FFR with satisfactory diagnostic accuracy. DVFFR, together with plaque analysis indices, yielded valuable predictions for MACE.

[A case of left pulmonary artery sling combined with congenital tracheal stenosis in an adult].

Pulmonary artery sling in adults is a rare congenital vascular malformation usually accompanied by tracheal and bronchial stenosis. Due to its high mortality risk and relatively poor prognosis, it has rarely been reported in adults. We reported a middle-aged patient who presented with shortness of breath, predominantly after activity, since childhood. He was diagnosed with "tracheal stenosis" in another hospital and received symptomatic treatment. The diagnosis of left pulmonary artery sling with congenital tracheal stenosis was confirmed by multi-slice spiral CT (MSCT), airway examination with flexible bronchoscope and 3D image post-processing system. Data from this case and the related literatures have been summarized and analyzed. This will help clinicians to improve their level of diagnosis and treatment.

[The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer].

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Genome-wide re-sequencing reveals population structure and genetic diversity of Bohai Black cattle.

Bohai Black (BHB) cattle, one of eight representative indigenous breeds in China, is well known for its high resistance to disease, endurance under unfavorable feeding conditions and excellent meat quality. Over recent, the number of BHB cattle has decreased sharply. To investigate the population structure and genetic diversity of this breed, the whole-genome data of 35 individuals from a conservation farm were obtained using the Illumina 150 bp paired-end platform. The results of the genetic structure and diversity analyses showed that BHB cattle had mixed Bos taurus and Bos indicus ancestry, close phylogenic relationships with Jiaxian Red and Luxi cattle and abundant genetic diversity. The bulls tested here could be divided into six families. This study presents a comprehensive evaluation of the genetic structure and diversity of the BHB cattle, and lays the theoretical basis for conservation and utilization of the valuable germplasm resource.

[Technology update and field expansion of bronchoscopy interventional diagnosis in 2021].

In recent years, with the rapid development of interventional pulmonary diseases, new instruments and new concepts are constantly updated. The increased detection rate of pulmonary nodules increases the demand of patients. These factors jointly promote the continuous progress of bronchoscopy diagnosis and treatment technology. The following techniques including thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (R-EBUS), and navigation bronchoscopy including virtual navigation bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB), robotic-assisted bronchoscopy (RAB), frozen biopsy for the diagnosis of diffuse lung diseases are particularly prominent and important in clinical practice. This paper reviews the progress and application of bronchoscopy in interventional diagnosis through the review of literature published in 2021.

[Efficacy of selective bronchial occlusion in the treatment of biliary bronchial fistula].

Objective: To analyze the effect of selective bronchial occlusion (SBO) in the treatment of biliary bronchial fistula (BBF). Methods: Eight patients with BBF that without biliary obstruction admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Naval Medical University from January 1, 2015 to December 31, 2021 were included in this study. Bronchial silicone plug (6 cases) and autologous blood+thrombin (2 cases) were used as sealing materials for SBO treatment for the first time. Among the 7 patients who underwent subsequent closure treatment, 5 cases were blocked by bronchial silicone plug, 1 case was blocked by "bronchial silicone plug+bullet-covered stent" and 1 case was blocked by "bronchial silicone plug+bronchial one-way valve". The clinical data related to SBO treatment were collected and patients were followed up, and the therapeutic effect of SBO on BBF was analyzed. Results: The age of BBF onset was (58±9) years old, including 6 males. Among the 6 patients who used bronchial silicone plug as plugging material in the first SBO treatment, 1 case was successfully plugged, 2 cases did not achieve symptoms relief after plugging, 2 cases coughed up the plugging device immediately after surgery, and 1 case developed a new fistula. Autologous blood and thrombin were used as sealing materials in 2 patients, and both failed. Among the 7 patients who received subsequent closure treatment, bronchial silicone plug+bullet-covered stent (1 case) and bronchial silicone plug+bronchial unidirectional valve (1 case) were successful. After 2-6 times of bronchial silicone plug (5 cases), fistula were successfully blocked in 3 cases, and the frequency and volume of bile-like sputum decreased by 50% or more in 2 cases. The main postoperative complications were fever and cough (expectoration) in 7 and 6 cases, respectively. During the follow-up period, 2 patients were lost to follow-up, and the remaining 6 patients were followed up for 2-31 months. During the follow-up period, the effect of closure treatment was basically stable, and there was no death case. Conclusion: SBO therapy provides a safe and feasible palliative treatment for BBF.

[A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting].

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.

Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head.

OBJECTIVE: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control. DESIGN: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC). RESULTS: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage. CONCLUSIONS: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH.

[Analysis of surgical strategy of percutaneous endoscopic lumbar discectomy in young and middle-aged double-segment patients with lumbar disc herniation].

OBJECTIVE: To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation. METHODS: Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications. RESULTS: The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group. CONCLUSION: For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.

[Association of hyperuricemia-induced renal damage with sirtuin 1 and endothelial nitric oxide synthase in rats].

Objective: To investigate the association of hyperuricemia-induced renal damage with sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in rats. Methods: Using the random number table method, 32 Sprague-Dawley rats were randomly divided into 4 groups: control group, model A group (the model was generated using oxonic acid potassium salt alone), model B group (hyperuricemia model was generated using oxonic acid potassium salt combined with uric acid) and resveratrol group, with 8 rats in each group. The experiment lasted 12 weeks. Serum uric acid and cystatin C levels were monitored regularly. In week 12, serum creatinine and urea nitrogen levels were measured, and the kidneys were extracted. The expression of SIRT1 and eNOS in renal tissues was measured and determined by immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. Immunohistochemistry of alpha-smooth muscle actin combined with Masson staining was employed to evaluate the degree of renal fibrosis, and pathological changes were observed based on hematoxylin and eosin staining. Results: In week 12, the uric acid levels in both the model A and model B groups were higher than those in the control group [(316±43) µmol/L, (297±40) µmol/L vs (118±44) µmol/L, both P<0.05]. The levels of cystatin C in the model A, model B, and resveratrol groups were all higher than those in the control group [(156±20) ng/ml, (143±29) ng/ml, (128±26) ng/ml vs (62±18) ng/ml, all P<0.05]. Creatinine levels were higher in the model A and model B groups than those in the control group [(68.5±10.3) µmol/L, (64.5±13.9) µmol/L vs (43.2±10.6) µmol/L, both P<0.05]. The levels of uric acid, cystatin C and creatinine in the resveratrol group were lower than those in the model A group (all P<0.05). Immunohistochemistry, RT-qPCR, and Western blotting for renal SIRT1 and eNOS showed that the expression in the model A and model B groups was inhibited, while the expression in the resveratrol group was not significantly inhibited, compared with that in the control group. Microscopically, obvious abnormalities were not found in the renal tissue of the control group. Renal inflammatory cell aggregation and edema occurred, and interstitial fibrosis was obvious in both the model A and model B groups, while these lesions in the resveratrol group were significantly improved. Conclusions: Hyperuricemia may cause renal injury by inhibiting the expression of SIRT1 and eNOS.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Retrospective study of the functional and oncological outcomes of conformal sphincter preservation operation in the treatment of very low rectal cancer.

BACKGROUND: Conformal sphincter preservation operation (CSPO) is a new surgical procedure for very low rectal cancers (within 4-5 cm from the anal verge). CSPO preserves more of the dentate line and distal rectal wall and also avoids injuring nerves in the intersphincteric space, resulting in satisfactory anal function after resection. The aim of this study was to analyze the short-term surgical results and long-term oncological and functional outcomes of CSPO. METHODS: Consecutive patients with very low rectal cancer, who had CSPO between January 2011 and October 2018 at Changhai Hospital, Shanghai were included. Patient demographics, clinicopathological features, oncological outcomes and anal function were analyzed. RESULTS: A total of 102 patients (67 men) with a mean age of 56.9 ± 10.8 years were included. The median distance of the tumor from the anal verge was 3 (IQR, 3-4) cm. Thirty-five patients received neoadjuvant chemoradiation (nCRT). The median distal resection margin (DRM) was 0.5 (IQR, 0.3-0.8) cm. One patient had a positive DRM. All circumferential margins were negative. There was no perioperative mortality. The postoperative complication rate was 19.6%. The median duration of follow-up was 28 (IQR, 12-45.5) months. The local recurrence rate was 2% and distant metastasis rate was 10.8%. The 3-year overall survival and disease-free survival rates were 100% and 83.9%, respectively. The mean Wexner incontinence and low anterior resection syndrome scores 12 months after ileostomy reversal were 5.9 ± 4.3, and 29.2 ± 6.9, respectively. CONCLUSIONS: For patients with very low rectal cancers, fecal continence can be preserved with CSPO without compromising oncological results.

[Ovarian metastases of pancreatic ductal adenocarcinomas: the clinicopathological characteristics and outcomes of 10 cases].

Objective: To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma. Methods: Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed. Results: The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months. Conclusions: Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.

[The clinicopathologic features and prognostic analysis of pancreatic metastasis from clear cell renal cell carcinoma].

Objective: To investigate the clinicopathologic features and prognosis of the patients who had clear cell renal cell carcinoma (CCRCC) with metastasis to the pancreas. Methods: From Jan, 2000 to Dec, 2018, 18 patients with clear cell renal cell carcinoma (CCRCC) and had pathologically diagnosed metastasis to the pancreas were enrolled at Peking Union Medical College Hospital. The clinical and pathological data were retrospectively analyzed. Results: 11 out of 18 patients were male, and the other 7 were female. The average age of onset of CCRCC was 51.4 years. 8 cases (44.4%) occurred in the left kidney, and the other 10 cases (55.6%) with right kidney tumor. Three patients had synchronous pancreatic metastasis, and the other 15 patients had metachronous pancreatic metastasis. The median time from CCRCC onset to pancreas metastasis was 156 months. The main complaints of pancreas metastasis were abdominal pain, jaundice, gastrointestinal bleeding, nausea, weakness, loss of weight and so on. Seven patients (38.9%) had single lesion of pancreas, while 11 patients (66.1%) had multiple lesions of pancreas. Nine patients (50%) had other organs metastasis besides pancreatic metastasis at the same time. Five patients underwent pancreatic metastasis resection, while 15 patients received oral tyrosine kinase inhibitor(TKI). The mean follow-up was 171.7 months(1~361.5 months) and 5 patients died. The median overall survival (mOS) was 122 months, and the 5 year-survival rate was 81.4%. In univariate analysis, synchronous metastasis to the pancreas, relapse after 10 years, Memorial Sloan Kettering Cancer Center prognostic index, International Metastatic Renal Cell Carcinoma Database Consortium index were all significant parameters for patients'survival. Conclusions: Metastasis to the pancreas from clear cell renal cell carcinoma were rare. These patients had better survival outcomes, especially those relapsing after ten years. Pancreatic metastasis resection had no significant benefit on patient's survival.

[Short-term effect of sodium zirconium cyclosilicate on potassium lowering in chronic kidney disease patients with hyperkalemia].

Objective: To investigate the efficacy of sodium zirconium cyclosilicate on emergency correction of hyperkalemia in chronic kidney disease patients. Methods: Patients with chronic kidney disease who were admitted to the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from May to June 2020 were selected. Those who had hyperkalemia and took sodium zirconium cyclosilicate powder were finally included. The patient's clinical data and laboratory results were collected. Results: A total of 24 results were included from 21 patients. The age of patients was (48.9±13.5) years old. Fourteen patients were male, and 7 patients were female. After 2 hours of administration, the venous potassium level decreased from (5.85±0.52) mmol/L to (5.15±0.43) mmol/L (P<0.001, n=21), with an average decline of (0.71±0.43) mmol/L. Meanwhile, the arterial potassium level decreased from (5.50±0.40) mmol/L to (4.88±0.33) mmol/L (P<0.001, n=10), with an average decline of (0.62±0.29) mmol/L. Based on the initial venous potassium level, the patients were further divided into three groups. The average potassium decrease in<5.5 mmol/L group (4 patients), 5.5-<6.0 mmol/L group (11 patients) and ≥6.0 mmol/L group (6 patients) was (0.46±0.26) mmol/L, (0.62±0.38) mmol/L and (1.04±0.45) mmol/L, respectively. There was statistically significant difference of potassium reduction among the three groups (P=0.045). Moreover, the extent of potassium reduction was positively correlated with baseline venous potassium level (r=0.603, P=0.004, n=21). The study did not reveal any treatment-related adverse event. Conclusion: Sodium zirconium cyclosilicate powder can rapidly and effectively reduce the serum potassium level in chronic kidney disease patients with hyperkalemia.

[Characteristics and outcomes of primary angiosarcoma].

Objective: The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods: The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan-Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results: A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were (7.4±7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+ Ⅱ) and 40 patients had metastatic disease (stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow-up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P=0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P=0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment (5.6 months, P=0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P<0.05). Conclusions: Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.

[The 472nd case: dyspnea, pulmonary shadows, abnormalities of whole blood cells].

A 54-year-old man was admitted to respiratory department with chief complaints of recurrent cough and dyspnea. Chest imaging showed multiple patchy shadows and interstitial changes. Evidence of infectious diseases was not definite, and antibiotic treatments were not effective. In the meantime, myelodysplasia syndrome was diagnosed with pancytopenia. The pathologic findings of transbronchoscopic lung biopsyshowed chronic inflammatory interstitial changes, suggesting a clinical diagnosis of organizing pneumonia. After glucocorticoids treatment, his condition aggravated. The second percutaneous lung biopsy showed the infiltration of a large number of neutrophils. Therefore, the final diagnosis of myelodysplasia syndrome with Sweet syndrome was made. Then glucocorticoids and supportive treatment were given This case may improve physicians' understanding of myelodysplasia syndrome complicated with Sweet syndrome.

[The study of pleural effusion supernatant cell-free tumor DNA in tumor mutational burden assessment of advanced lung cancer].

Objective: To evaluate the feasibility of cell-free tumor DNA in pleural effusion supernatant for assessing the tumor mutational burden (TMB) of advanced lung cancers. Methods: From December 2016 to August 2018, 34 lung cancer patients (19 males and 15 females) with pleural effusion were enrolled at Zhongshan Hospital, Fudan University. The median age of the patients was 65 (range, 34-85) years. Before systemic or local antitumor therapy, tumor specific mutations in tumor tissue, pleural effusion supernatant, pleural effusion sediment, and plasma samples from these patients were examined using targeted next-generation sequencing, and TMB levels were calculated respectively. Subgroup analysis was based on smoking history and driver mutation status. Statistical differences were determined using SPSS 16.0 software, and individual groups were compared using the one-way analysis of variance (ANOVA) and LSD-t test. Results: The median TMB level of pleural effusion supernatant was 6.23 mutations/Mb, similar to that of tumor tissue (6.23 vs 6.86 mutations/Mb, t=1.174, P=0.245), but significantly higher than that of pleural effusion sediment (2.49 mutations/Mb, t=3.044, P=0.003) and plasma (2.49 mutations/Mb, t=2.464, P=0.016). Compared with tumor tissue in TMB assessment, pleural effusion supernatant had a positive percentage agreement of 52% (9/17), and a negative percentage agreement of 65% (11/17). Subgroup analysis showed that the TMB level was higher in smokers (n=11) than that in non-smokers (n=23, 14.4 vs 5.4 mutations/Mb, t=3.238, P=0.003). Conclusion: For advanced lung cancer patients with pleural effusion, pleural effusion supernatant is a promising substitute to tumor tissue for TMB assessment, which is a potential biomarker for immunotherapy.

[The efficacy and safety of tiotropium/olodaterol fixed-dose combination in Chinese patients with chronic obstructive pulmonary disease: a pooled subgroup analysis of TONADO 1+2].

Objective: To compare the efficacy and safety profiles of tiotropium/olodaterol with the mono-components in Chinese and total study population from TONADO trial. Methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase Ⅲ TONADO studies (TONADO 1+2), patients received tiotropium/olodaterol, tiotropium, or olodaterol via the Respimat(®) Inhaler (Boehringer Ingelheim, Germany). Primary end points were forced expiratory volume in 1 second (FEV(1)) area under the curve from 0 to 3 hours (AUC(0-3h)) response and trough FEV(1) response, and St George's respiratory questionnaire (SGRQ) total score at 24 weeks. Adverse events were also collected. This subgroup analysis only focused on the efficacy and safety of the drug at the approved dose in China. Results: 548 Chinese patients were randomized, aged 41 to 82 years [mean age, (63±8) years] and most were male (526, 96%), 111 received tiotropium/olodaterol 5/5 µg, and 127 received tiotropium 5 µg and 95 received olodaterol 5 µg. The baseline characteristics of these groups were similar. After 24 weeks, treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg and olodaterol 5 µg resulted in an adjusted mean FEV(1) AUC(0-3h) response of 0.240, 0.157 and 0.079 L, and trough FEV(1) response of 0.117, 0.068 and-0.001 L, respectively. Tiotropium/olodaterol 5/5 µg significantly improved SGRQ scores in Chinese patients compared with olodaterol 5 µg (32.729 and 37.202, respectively). Generally, the safety profile of tiotropium/olodaterol was comparable with mono-components in 52 weeks. Conclusion: Compared with tiotropium or olodaterol, tiotropium/olodaterol in Chinese patients provided significant improvement in lung function and quality of life, and the safety profiles were similar.