Publications by authors named "Hairong Xu"

103 Publications

[Application of three-dimensional printing technology in treatment of limb bone tumors].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2022 Jul;36(7):790-795

Department of Orthopaedic Oncology Surgery, Beijing Jishuitan Hospital, Beijing, 102208, P. R. China.

With the developing of three-dimensional (3D) printing technology, it is widely used in the treatment of bone tumors in the clinical orthopedics. Because of the great individual differences in the location of bone tumor, resection and reconstruction are difficult. Based on 3D printing technology, the 3D models can be prepared to show the anatomical part of the disease, so that the surgeons can create a patient-specific operational plans based on better understand the local conditions. At the same time, preoperative simulation can also be carried out for complex operations and patient-specific prostheses can be further designed and prepared according to the location and size of tumor, which may have more advantages in adaptability. In this paper, the domestic and international research progress of 3D printing technology in the treatment of limb bone tumors in recent years were reviewed and summarized.
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http://dx.doi.org/10.7507/1002-1892.202203006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288913PMC
July 2022

Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States.

Transplant Cell Ther 2022 May 21. Epub 2022 May 21.

Medical College of Wisconsin/Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin. Electronic address:

Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting. A total of 1297 patients receiving commercial axi-cel between 2017 and 2020 were selected from the Center for International Blood and Marrow Transplant Research's data registry, of whom 739 (57%) would have been ineligible for inclusion in the ZUMA-1 cohort. Efficacy and safety outcomes were described for the entire cohort and by ZUMA-1 eligibility. Their associations with age, Eastern Cooperative Oncology Group Performance Score, and comorbidities were evaluated using multivariable logistic and Cox regressions. At a median follow-up of 12.9 months, the overall response rate (ORR) was 73%, with a 56% complete response (CR) rate. Median overall survival (OS) and progression-free survival (PFS) were 21.8 months (95% confidence interval [CI], 17.4 to 28.8 months) and 8.6 months (95% CI, 6.5 to 12.1 months), respectively. Duration of response (DOR) was comparable in the ZUMA-1 ineligible patients and ZUMA-1 eligible patients (62% by 1 year [95% CI, 57% to 66%] versus 67% [95% CI, 62% to 72%]). Patients age ≥65 years had favorable ORR (odds ratio [OR], 1.39; 95% CI, 1.05 to 1.83) despite having a higher risk of cytokine release syndrome (CRS) (OR, 1.41; 95% CI, 1.02 to 1.94) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR, 1.77; 95% CI, 1.39-2.26). Eastern Cooperative Oncology Group Performance Score ≥2 was associated with inferior efficacy outcomes (OR for ORR, 0.32; 95% CI, 0.18-0.56; hazard ratio [HR] for OS, 3.27; 95% CI, 2.37 to 4.52) and higher incidence of ICANS (OR, 2.63; 95% CI, 1.40 to 4.93). The patients ineligible for ZUMA-1 still had a durable response with axi-cel. Elderly patients had favorable efficacy outcomes despite higher rates of CRS and ICANS. Patient selection for standard-of-care axi-cel should consider comorbidities and risk-to-benefit ratio rather than be based strictly on ZUMA-1 eligibility.
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http://dx.doi.org/10.1016/j.jtct.2022.05.026DOI Listing
May 2022

Neoadjuvant radiotherapy for soft tissue sarcoma in China: a preliminary result.

Ann Transl Med 2022 Apr;10(8):452

Department of Orthopaedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing, China.

Background: Neoadjuvant radiotherapy (RT) for soft tissue sarcoma (STS) is widely used abroad, but rarely reported in China. We assessed the preliminary clinical outcomes of preoperative RT followed by surgery in patients with STS.

Methods: A total of 19 patients (14 male, 5 female) with intermediate- or high-grade primary STS were treated with neoadjuvant RT in 2-Gy fractions over 25 sessions for a total dose of 50 Gy. Surgical resection was then performed. The pathologic specimens were reviewed for percentage of residual tumor cells. And the skin complications, wound complications and local recurrence and distant metastasis were also evaluated.

Results: After neoadjuvant RT, 2 patients had progressive disease (PD), 6 showed a partial remission (PR), and 11 demonstrated stable disease (SD). The objective response rate (ORR) was 31.6%, and the disease control rate (DCR) was 89.5%. The median follow-up was 14.3 months (11.9-24.7 months). Six patients (31.6%) had wound complications: 3 cases of epidermal complications and 3 of severe complications (15.8%) comprising 2 cases of skin flap necrosis, and 1 case of local hematoma. The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) histopathological response score was used to evaluate the post-RT response. A total of 9 patients (47.4%) achieved pathological complete remission (pCR). No recurrence was found, but metastasis occurred in 2 patients (10.5%) in the preliminary follow-up.

Conclusions: Neoadjuvant RT for STS has a quietly high DCR and pathological remission rate. Surgical wound complications can be controlled after neoadjuvant RT.
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http://dx.doi.org/10.21037/atm-22-98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096360PMC
April 2022

Avoiding Misdiagnosis and Missed Diagnosis for Appropriately Treating Spinal Osteoid Osteomas: A Single-Center Experience.

Orthop Surg 2022 May 18;14(5):868-875. Epub 2022 Apr 18.

Department of Orthopaedic Oncology, Beijing Jishuitan Hospital, Beijing, China.

Objectives: To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients.

Methods: We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery.

Results: Thirty-seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X-ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow-ups.

Conclusions: Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.
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http://dx.doi.org/10.1111/os.13280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087446PMC
May 2022

Development and Validation of a Transfusion Risk Score for Patients Receiving Maintenance Hemodialysis.

Kidney360 2021 06 9;2(6):948-954. Epub 2021 Apr 9.

Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota.

Background: In patients on dialysis with anemia, avoiding red blood cell transfusions is preferable. We sought to develop and validate a novel transfusion prediction risk score for patients receiving maintenance hemodialysis.

Methods: This retrospective cohort study used United States Renal Data System data to create a model development cohort (patients who were point prevalent and on hemodialysis on November 1, 2012) and a validation cohort (patients who were point prevalent and on hemodialysis on August 1, 2013). We characterized comorbidity, inflammatory conditions, hospitalizations, anemia and anemia management, iron parameters, intravenous iron use, and vitamin D use during a 6-month baseline period to predict subsequent 3-month transfusion risk. We used logistic least absolute shrinkage and selection operator regression. In an exploratory analysis, model results were used to calculate a score to predict 6- and 12-month hospitalization and mortality.

Results: Variables most predictive of transfusion were prior transfusion, hemoglobin, ferritin, and number of hospital days in the baseline period. The resulting c-statistic in the validation cohort was 0.74, indicating relatively good predictive power. The score was associated with a significantly increased risk of subsequent mortality (hazard ratios 1.0, 1.22, 1.26, 1.54, 1.71, grouped from lowest to highest score), but not with hospitalization.

Conclusions: We developed a transfusion prediction risk score with good performance characteristics that was associated with mortality. This score could be further developed into a clinically useful application, allowing clinicians to identify patients on hemodialysis most likely to benefit from a timely, proactive anemia treatment approach, with the goal of avoiding red blood cell transfusions and attendant risks of adverse clinical outcomes.
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http://dx.doi.org/10.34067/KID.0004512020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791373PMC
June 2021

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.

Nat Med 2022 04 21;28(4):735-742. Epub 2022 Mar 21.

Moffitt Cancer Center, Tampa, FL, USA.

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.
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http://dx.doi.org/10.1038/s41591-022-01731-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018426PMC
April 2022

The prospective multiple-centre randomized controlled clinical study of high-dose amoxicillin-proton pump inhibitor dual therapy for infection in Sichuan areas.

Ann Med 2022 Dec;54(1):426-435

Sichuan Anyue County People's Hospital, Ziyang, China.

Objectives: To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with infection.

Methods: A total of 971 positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether was eradicated.

Results: There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of between dual therapy and quadruple therapy were 88.31% and 85.26% (=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (<.01)).

Conclusions: For the initial treatment of infection, the high-dose dual therapy regimen has the same efficacy as the bismuth-containing quadruple therapy regimen, good compliance, less adverse reactions and high safety, so it can be recommended as the empirical first-line treatment regimen for the eradication of (KY2019173).
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http://dx.doi.org/10.1080/07853890.2022.2031269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812792PMC
December 2022

Study of imaging changes following preoperative denosumab for giant cell tumor of bone.

J Bone Oncol 2022 Feb 31;32:100410. Epub 2021 Dec 31.

Department of Orthopedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing, People's Republic of China.

Background: The changes in the characteristics of the tumor blood supply of giant cell tumor of bone over time after treatment with denosumab remain unclear. The purpose of this study was to evaluate the change in the blood supply imaging characteristics of giant cell tumor of bone after preoperative denosumab treatment and to provide evidence for evaluating the reasonable time for preoperative treatment.

Methods: A total of 59 patients with giant cell tumor of bone who were treated in our hospital from 2014 to 2019 were enrolled in the study. All patients underwent enhanced CT examination of the tumor site before denosumab treatment and every month after treatment. The plain CT value and enhanced CT value of the tumor were measured, and the CT enhancement rate of the tumor was calculated. The change in the CT enhancement rate of the tumor over time after denosumab treatment was analyzed.

Results: The average tumor enhancement rates were 2.14 (1.22-4.05), 1.60 (1.12-2.53), 1.38 (1.02-2.24), and 1.25 (1-2.11) before denosumab treatment and one month, three months, and six months after treatment, respectively. After denosumab treatment, the average monthly CT enhancement rate decreased as follows: 0.54 (25.2%) in the first month, 0.11 (5.15%) in the second to third months, and 0.04 (1.87%) in the fourth to sixth months. The tumor enhancement rate was no longer significantly reduced three months post-treatment. There was a significant correlation between the reduction in the CT enhancement rate and the initial CT enhancement rate (P = 0.000).

Conclusion: The preoperative application of denosumab can reduce tumor blood supply. The decrease in the blood supply is the most significant in the initial stage of treatment. Following treatment, the decrease in the blood supply gradually reduces over time. Therefore, for the purpose of reducing intra-operative bleeding and facilitating surgery, application of denosumab treatment is not recommended more than three months before surgery.
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http://dx.doi.org/10.1016/j.jbo.2021.100410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760557PMC
February 2022

Prognostic value and predictive biomarkers of phenotypes of tumour-associated macrophages in colorectal cancer.

Scand J Immunol 2022 Apr 10;95(4):e13137. Epub 2022 Jan 10.

Department of General Surgery, Luoyang Central Hospital Affiliated of Zhengzhou University, Luoyang, China.

Background: The roles of different subtypes of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remain controversial. In this study, different subtypes of TAMs were investigated as prognostic and predictive biomarkers for CRC.

Methods: Expressions of CD68, CD86 and CD163 were investigated by immunohistochemistry (IHC) and immunofluorescence (IF), and the correlation between the expression of CD86 and CD163 was calculated in colorectal cancer tissues from 64 CRC patients.

Results: The results showed that high expressions of CD86 and CD68 CD86 TAMs as well as low expression of CD163 and CD68 CD163 TAMs were significantly associated with favourable overall survival (OS). The level of CD86 protein expression showed a negative correlation with CD163 protein expression. In addition, CD86 protein expression remarkably negatively correlated with tumour differentiation and tumour node metastasis (TNM) stage, while CD163 protein expression significantly positively correlated with tumour differentiation and tumour size. As an independent risk factor, high expression of CD86 TAMs had prominently favourable prognostic efficacy, while high expression of CD68 CD163 TAMs had significantly poor prognostic efficacy.

Conclusions: These results indicate that CD86 and CD68 CD163 TAMs as prognostic and predictive biomarkers for CRC.
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http://dx.doi.org/10.1111/sji.13137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286461PMC
April 2022

Chemical elucidation of an arabinogalactan from rhizome of Polygonatum sibiricum with antioxidant activities.

Int J Biol Macromol 2021 Nov 11;190:730-738. Epub 2021 Sep 11.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China. Electronic address:

Polygonatum sibiricum is traditionally used as Chinese medicine for immunity enhancement. Exploration of polysaccharides from Polygonatum species would provide a wider insight into the studies on their chemical structures and function activities. In this study, the alkali-extracted polysaccharide from P. sibiricum (PSP) was isolated and examined. The polysaccharide was firstly isolated by ion-exchange chromatography equipped with DE52 column, followed by isolated through Superdex-200 column. The obtained PSPJWA fraction was a homogenous one with average molecular weight of 141 kDa. The monosaccharide composition was galactose, arabinose and rhamnose in a ratio of 14:4:1. The glycosidic linkages of PSPJWA fraction were indicated to be Araf-(1→, →5)-Araf-(1→, →3,5)-Araf-(1→, Galp-(1→, →4)-Galp-(1→, →4,6)-Galp-(1→ and →2,4)-Rhap-(1→ residue by methylation analysis. NMR and enzymatic studies showed that PSPJWA was a novel arabinogalactan-type structure. PSPJW polysaccharides with different molecular weight and similar chemical structure had different antioxidant activities. Together, P. sibiricum polysaccharide has the potential to be a natural antioxidant.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.038DOI Listing
November 2021

Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus.

Clin Res Hepatol Gastroenterol 2022 02 29;46(2):101781. Epub 2021 Jul 29.

Department of Oncology Biotherapy, The Third Affiliated Hospital of Naval Medical University, No. 700 North Moyu road, Jiading district, 201805 Shanghai, China. Electronic address:

Background: The views regarding the associations between metformin use and hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients are divisive. Thus we summarized all available published studies evaluating the relationship between metformin therapy and HCC survival and risk, and aim to conduct an updated meta-analysis study to more accurately clarify the association.

Methods: We searched for articles regarding impact of metformin use on risk and mortality of HCC in DM and published before April 2021 in databases (PubMed and Web of Science). We used STATA 12.0 software to compute odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) to generate a computed effect size and 95% CI.

Results: The present study showed that metformin use was associated with a decreased risk of HCC in DM with a random effects model (OR/RR = 0.59, 95% CI 0.51-0.68, I2 = 96.5%, p < 0.001). In addition, the study indicated that metformin use was associated with a decreased all-cause mortality of HCC in DM with a random effects model (HR = 0.74, 95% CI 0.66-0.83, I2 = 49.6%, p = 0.037).

Conclusion: In conclusion, our studies support that the use of metformin in DM patients is significantly associated with reduced risk and all-cause mortality of HCC. And more prospective studies focusing on the metformin therapy as a protective factor for HCC are needed to verify the accuracy of the findings.
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http://dx.doi.org/10.1016/j.clinre.2021.101781DOI Listing
February 2022

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2.

Cell Res 2021 09 15;31(9):1011-1023. Epub 2021 Jul 15.

Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.
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http://dx.doi.org/10.1038/s41422-021-00531-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646PMC
September 2021

Detection of BCOR gene rearrangement in Ewing-like sarcoma: an important diagnostic tool.

Diagn Pathol 2021 Jun 8;16(1):50. Epub 2021 Jun 8.

Department of Pathology, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, Beijing, People's Republic of China.

Background: BCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, thus making them difficult to diagnose. The aim of this study was to explore the role of molecular techniques in the diagnosis of BCS.

Methods: Twenty-three cases of EWSR1 rearrangement-negative undifferentiated small round cell sarcomas (Ewing-like sarcoma) were analyzed for the presence of BCOR gene rearrangement by Fluorescence in situ hybridization (FISH) and Reverse Transcription -Polymerase Chain Reaction (RT-PCR). The clinicopathological features of the positive cases were also reviewed. Fifteen additional cases were used as negative controls.

Results: Eight cases were found with BCOR gene rearrangement by FISH and reappraised as BCS. The patients ranged in age from 8 to 20 years old, with a male predominance (M:F = 6:2). All tumors were located in the lower extremities. The tumor locations were more common in bone (n = 6) than deep soft tissue (n = 2). Histologically, 7 of 8 tumors were predominately composed of spindle or ovoid cells. The tumor cells were usually arranged in solid hypercellular sheets without a distinct architectural pattern. IHC showed expression of TLE1 (100%), CCNB3 (88%), BCOR (71%). RT-PCR for BCOR-CCNB3 fusion transcript was positive in 7 of 8 cases. Pre-operative chemotherapy resulted in eradication of tumors in 5 patients after a follow-up of 7 to 42 months.

Conclusions: Efficient diagnosis of BCOR rearranged sarcomas is achieved by the using a combination of FISH and RT-PCR assays.
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http://dx.doi.org/10.1186/s13000-021-01114-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185946PMC
June 2021

Chemotherapy-induced amenorrhea and its effects on fertility in long-term female survivors of classic osteosarcoma.

Support Care Cancer 2021 Oct 26;29(10):5999-6004. Epub 2021 Mar 26.

Bone Oncology, Beijing Jishuitan Hospital, 31 east street of Xinjiekou, Xicheng District, Beijing, China.

Purpose: To explore the effect of chemotherapy-induced amenorrhea (CIA) on female osteosarcoma patients' fertility function, we investigated and analyzed their marital status, fertility, and menstrual status in a retrospective cohort study.

Methods: We selected female osteosarcoma patients from database from January 2004 to December 2013. Patients' characteristics such as age, tumor location, marital status, menstrual status, and fertility status were collected. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 22.

Results: A total of 122 female patients met these criteria and finally responded by questionnaire and telephone follow-up. The marriage rate of female osteosarcoma survivors was 50.8% (62/122), which was significantly lower than the control group (p = 0.000). The average marriage age of female osteosarcoma survivors was 25.5, which was obviously higher than the control group (p = 0.000). CIA occurred in 46 (36.1%) patients. We then found that the incidence of CIA was higher in older patients. (p = 0.011). All of the married patients wanted to have children, and 67.8% (42/62) of them had given birth after chemotherapy. The fertility of married patients with CIA was significantly reduced compared to that of married patients without CIA. (p = 0.001).

Conclusions: The patients with CIA have higher risk of impaired reproductive function than those who did not. Fertility preservation option before the start of the chemotherapy is important. And it is much value to record menstrual pattern and detect sex steroid levels after 6 months of therapy in order to be able to evaluate the fertility status.
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http://dx.doi.org/10.1007/s00520-021-06069-0DOI Listing
October 2021

Structure elucidation of arabinogalactoglucan isolated from Sedum sarmentosum Bunge and its inhibition on hepatocellular carcinoma cells in vitro.

Int J Biol Macromol 2021 Jun 16;180:152-160. Epub 2021 Mar 16.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, PR China. Electronic address:

Sedum sarmentosum Bunge (SS) is clinically used as Chinese medicine for hepatitis related diseases treatment. The purpose of this study was to explore the chemical structures of polysaccharides from this plant. A neutral polysaccharide (SSWP) was isolated and purified by ion-exchange chromatography and Superdex-75 column. The obtained SSWP was a homogenous one with a molecular weight of 21.5 kDa according to the high-performance gel permeation chromatography. The major monosaccharide composition of SSWP was arabinose, glucose and galactose in a molar ratio of 2.4:1:1.8. The methylation analysis showed that SSWP consists mainly of Araf-(1→, →5)-Araf-(1→, →3,5)-Araf-(1→, →4)-Galp-(1→, →4)-Glcp-(1→. The NMR result and enzymatic digestion data comprehensively indicated that SSWP was a novel arabinogalactoglucan-type structure. The anticancer assay in vitro exhibited that SSWP could effectively inhibit 48.9% of Huh-7 cells growth at 50 μg/mL and arrest cells at S-phase, and induce tumor cells apoptosis. Together, polysaccharide from S. sarmentosum Bunge could be a potential natural antitumor agent.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.051DOI Listing
June 2021

Does Adding Femoral Lengthening at the Time of Rotation Hip Transposition After Periacetabular Tumor Resection Allow for Restoration of Limb Length and Function? Interim Results of a Modified Hip Transposition Procedure.

Clin Orthop Relat Res 2021 Jul;479(7):1521-1530

Department of Orthopedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University. Beijing, China.

Background: Reconstruction after pelvic tumor resection of the acetabulum is challenging. Previous methods of hip transposition after acetabular resection have the advantages of reducing wound complications and infections of the allograft or metal endoprosthesis but were associated with substantial limb length discrepancy. We therefore developed a modification of this procedure, rotation hip transposition after femur lengthening, to address limb length, and we wished to evaluate its effectiveness in terms of complications and functional outcomes.

Questions/purposes: In this study, we asked: (1) What were the Musculoskeletal Tumor Society scores after this reconstruction method was used? (2) What complications occurred after this reconstruction method was used? (3) What proportion of patients achieved solid arthrodesis (as opposed to pseudarthrosis) with the sacrum and solid union of the femur? (4) What were the results with respect to limb length after a minimum follow-up of 2 years?

Methods: From 2011 to 2017, 83 patients with an aggressive benign or primary malignant tumor involving the acetabulum were treated in our institution. Of those, 23% (19 of 83) were treated with rotation hip transposition after femur lengthening and were considered for this retrospective study; 15 were available at a minimum follow-up of 2 years (median [range], 49 months [24 to 97 months]), and four died of lung metastases before 2 years. No patients were lost to follow-up before 2 years. During the period in question, the general indications for this approach were primary nonmetastatic malignant bone tumor or a locally aggressive benign bone tumor that could not be treated adequately with curettage. There were seven men and 12 women with a median age of 43 years. Nine patients underwent Zones I + II resection, eight patients had Zones I + II + III resection, and two received Zones II + III resection. After tumor resection, rotation hip transposition after femur lengthening reconstruction was performed, which included two steps. The first step was to lengthen the femur with the insertion of an allograft. Two methods were used to achieve limb lengthening: a "Z" osteotomy and a transverse osteotomy. The second step was to take the hip transposition and rotate the femoral head posteriorly 10° to 20°. The median (range) operative time was 510 minutes (330 to 925 minutes). The median intraoperative blood loss was 4000 mL (1800 to 7000 mL). We performed a chart review on the 15 available patients for clinical and radiographic assessment of functional outcomes and complications. Arthrodesis and leg length discrepancy were evaluated radiographically.

Results: The median (range) Musculoskeletal Tumor Society score was 21 points (17 to 30). Eleven of 19 patients developed procedure-related complications, including six patients with allograft nonunion, two with deep infection, two with delayed skin healing, and one with a hematoma. Two patients had minor additional surgical interventions without the removal of any implants. Local recurrences developed in four patients, and all four died of disease. All seven patients treated with a Z osteotomy had bone union. Among the eight patients with transverse osteotomy, bone union did not occur in six patients. After hip transposition, stable iliofemoral arthrodesis was achieved in seven patients. Pseudarthrosis developed in the remaining eight patients. The median (range) lower limb length discrepancy at the last follow-up visit or death was 8 mm (1 to 42 mm).

Conclusion: Although complex and challenging, rotation hip transposition after femur lengthening reconstruction with a Z osteotomy provides acceptable functional outcomes with complications that are within expectations for resection of pelvic tumors involving the acetabulum. Because of the magnitude and complexity of this technique, we believe it should be used primarily for patients with a favorable prognosis, both locally and systemically. This innovative procedure may be useful to other surgeons if larger numbers of patients and longer-term follow-up confirm our results.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280007PMC
July 2021

Safety analysis of application of mediastinal CO2 aeration in mediastinal esophagectomy.

Ann Palliat Med 2020 Sep 4;9(5):3107-3114. Epub 2020 Aug 4.

Department of Cardiothoracic Surgery, the Third Affiliated Hospital to Soochow University, Changzhou, China.

Background: In recent years, minimally invasive esophagectomy (MIE) has been used gradually in esophageal surgery. The application of CO2 aeration in minimally invasive surgeries, especially in laparoscopic surgery, has been very mature. However, the application of CO2 aeration in mediastinal esophagectomy is still in the exploration stage. This study was designed to investigate the safety of mediastinal CO2 aeration in the mediastinal esophagectomy.

Methods: A total of 15 pigs were used to construct an experimental animal model of mediastinal CO2 aeration. The effects of different inflation pressures on the circulatory respiratory function of pigs were studied by detecting the relevant physiological parameters. Heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were monitored before ventilating CO2 (T0), and also monitored at 30 (T1), 60 (T2), 90 (T3) min after inflation and 30 min after deflation (T4). Arterial blood was collected for PaCO2, blood lactate concentration (cLac), PaO2/FiO2, SaO2, pH value, and cardiac output (CO) was measured by esophageal ultrasound.

Results: The results of animal experiments showed that under 5-10 mmHg CO2 inflation pressure, circulation function indicators (CVP, MAP, HR, CO) and respiratory function indicators (PaCO2, cLac, PaO2/FiO2, SaO2, pH value) in pigs had no significant difference compared with the indicators before inflation; and under 15 mmHg CO2 inflation pressure, CVP, HR, PaCO2 and blood cLac increased, while MAP, CO, PaO2, SaO2 and pH values decreased. The visual field using mediastinoscopy under 15 and 10 mmHg CO2 inflation pressure was better than that under 5 mmHg CO2 inflation pressure.

Conclusions: Mediastinal esophagectomy with 5-10 mmHg CO2 inflation pressure has no significant effect on the circulation and respiratory function of the body. Compared with the conventional non-inflated transseptal esophageal cancer (EC) surgery, it can provide a better surgical vision and reduce the difficulty of the surgery.
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http://dx.doi.org/10.21037/apm-20-804DOI Listing
September 2020

Retrospective database analysis of healthcare resource utilization and costs in patients who develop post-transplant lymphoproliferative disease within the first year following allogeneic hematopoietic stem cell transplants.

J Med Econ 2020 Oct 22;23(10):1159-1167. Epub 2020 Jul 22.

Atara Biotherapeutics, Inc., South San Francisco, CA, USA.

Aims: Healthcare resource utilization (HRU) and costs in post-transplant lymphoproliferative disease (PTLD) patients following allogeneic hematopoietic stem cell transplant (HCT) were evaluated in the USA.

Methods: MarketScan Commercial and Medicare Supplemental database claims from 01 July 2010 to 31 December 2017 were analyzed. Patients eligible for analysis received allogeneic HCT between 01 January 2011 to 31 December 2015, had ≥6 months of continuous enrollment before HCT, and had ≥1 claim for PTLD or ≥1 inpatient or ≥2 outpatient claims for a clinically-relevant lymphoma within 1 year following HCT (PTLD index = first claim of diagnosis). Patients with clinically-relevant lymphomas within 6 months before HCT were excluded. HRU and total paid amounts were assessed from the week before the HCT through 1-day pre-PTLD index (HCT to PTLD) and monthly from PTLD index through 1-year post-PTLD index. HRU is reported as mean (SD). Results were also provided by survival status.

Results: Overall, 92 patients were eligible for analysis. From HCT to PTLD, 98.9% of patients were hospitalized, with 1.7 (1.2) hospitalizations/patient. The average length of stay was 25.3 (22.2) days/patient. From HCT to PTLD, 98.9% of patients had outpatient services with 233.7 (261.1) services/patient and 91.3% of patients had a prescription fill with 32.9 (26.0) prescriptions/patient. In the first month post-PTLD index, 51.2% of patients were hospitalized. Mean paid amounts were $399,470/patient (range $7542-$1.7 M) from HCT to PTLD. Cumulative mean paid amounts 1-year post-PTLD were $429,043/patient. Total cost/patient/month was ∼7 times higher in patients who died ( = 49; $232,591) than those who lived ( = 43; $33,677). Costs were mainly driven by hospitalizations.

Limitations: Limitations include those inherent to retrospective analyses (i.e. miscoding, lack of clinical detail).

Conclusions: HRU and costs from HCT to PTLD were high and more than doubled within 1-year post-PTLD. PTLD patients who died had ∼7 times higher costs than those who lived, driven by hospitalizations. Effective treatments are needed to reduce the burden of PTLD.
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http://dx.doi.org/10.1080/13696998.2020.1793765DOI Listing
October 2020

Bone defect reconstruction with autologous bone inactivated with liquid nitrogen after resection of primary limb malignant tumors: An observational study.

Medicine (Baltimore) 2020 Jun;99(24):e20442

Department of Orthopedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing, People's Republic of China.

Surgical treatment of malignant bone tumors comprises tumor resection and reconstruction. The most commonly used reconstruction method is prosthesis replacement, which achieves good early function, but has a high long-term incidence of complications. Another reconstruction option is autologous bone replantation, which has the advantages of anatomical matching and no need for large bone bank support. Few studies have evaluated reconstruction with liquid nitrogen-inactivated autogenous bone.The present study aimed to evaluate the oncological results, bone healing results, complications, and indications of reconstruction with liquid nitrogen-inactivated autogenous bone grafts.The study population comprised 21 consecutive patients. The tumor site was the tibia in 9 cases, femur in 8, and humerus in 4. There were 37 osteotomy ends in total. After freezing and rewarming, the medullary cavity of the autogenous bone was filled with antibiotic bone cement. Seventeen patients received bilateral plate fixation, 2 received intramedullary nail and distal plate fixation, and 2 received single plate fixation.The average follow-up was 31 ± 6 months. Eighteen patients survived without tumors, and the 3-year survival rate was 80.4%. All cases had adequate surgical margins, but recurrence developed in 1 patient. Metastasis occurred in 3 patients, who all died of metastasis. Intraoperative inactivated bone fracture occurred in 1 patient, and screw breakage was found in 1 patient. Nonunion occurred at 1 humeral diaphysis osteotomy site, and 1 patient was lost to follow-up; the average healing time of the other 35 ends was 13 ± 6 months, and the bone healing rate was 97.2%. The average bone healing times in the metaphysis and diaphysis were 9 ± 3 months and 15 ± 6 months (P = .003). The average bone healing times in the upper and lower limbs were 16.6 ± 7.4 months and 12.3 ± 5.8 months (P = .020). The average Muscle and Skeletal Tumor Society score was 28 ± 3 (21-30) in the 18 survivors.Liquid nitrogen-inactivated autologous bone replantation for primary malignant limb tumor was safe and effective, as shown by the relatively low complication rate, high bone healing rate, and satisfactory postoperative function. This is a reliable biological reconstruction method for malignant bone tumors with specific site and bone destruction characteristics.
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http://dx.doi.org/10.1097/MD.0000000000020442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302590PMC
June 2020

Factors of Reflux Episodes With Post-reflux Swallow-induced Peristaltic Wave in Gastroesophageal Reflux Disease.

J Neurogastroenterol Motil 2020 07;26(3):378-383

Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background/aims: It is known that post-reflux swallow-induced peristaltic wave (PSPW) index represents the chemical clearance of the esophagus. However, few studies have explored why some reflux episodes could induce PSPW while others in the same patient could not. The purpose of this study is to investigate the characteristics of reflux episodes which could elicit PSPW.

Methods: In this study, 269 reflux episodes were detected, of which 90 with a PSPW and 179 without a PSPW. Comparisons were made between the characteristics of reflux episodes with a PSPW and without a PSPW. The characteristics were including nadir pH, pH drop, proximal extent (cm, sec), ascending velocity (cm/sec), volume clearance time, acid clearance time, percentage acidic (%), 15 to 60-minute acid burden (seconds), and 15- to 60-minute volume burden (seconds). The characteristics between the 2 groups were compared through performing Wilcoxon signed rank test.

Results: Reflux episodes followed by a PSPW were significantly associated with a higher proximal extent than those without a PSPW. After the reflux episodes, higher volume clearance time and larger volume burden were more likely to trigger a PSPW. However, there were no significant differences between the 2 groups in nadir pH, pH drop, ascending velocity, acid clearance time, percentage acidic, or acid burden.

Conclusions: The role of acid seems to be less important in a reflux episode inducing a PSPW. Proximal reflux episodes are more likely to induce a PSPW. The depression of volume clearance may also be an important factor in eliciting a PSPW.
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http://dx.doi.org/10.5056/jnm19115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329156PMC
July 2020

Author Correction: A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8 T-cell response and effective tumor control.

Nat Commun 2020 Apr 1;11(1):1716. Epub 2020 Apr 1.

Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-15532-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113269PMC
April 2020

A comparative study of sulfated tara gum: RSM optimization and structural characterization.

Int J Biol Macromol 2020 May 10;150:189-199. Epub 2020 Feb 10.

College of Life Science, Northwest Normal University, Lanzhou 730070, People's Republic of China; Bioactive Products Engineering Research Center For Gansu Distinctive Plants, Northwest Normal University, Lanzhou 730070, People's Republic of China. Electronic address:

Interest in galactomannans and its derivatives as a functional health supplement is growing based on physicochemical properties. In this work, the optimized conditions of sulfated tara gum (STG) with a maximum DS of 0.66 by box-behnken design (BBD) were obtained as following: ratio of chlorosulfonic acid/pyridine 3:1, reaction time 4 h and reaction temperature 40 °C. The structure features of STG such as the degree of substitution (DS), substitution position, weight average molar mass (M), monosaccharide components and chain conformation were investigated. Decreasing of M, the increasing of Z-average radius of gyration (〈S〉) and specific volume for gyration (SV) were obtained by SEC-MALLS. In addition, the structural properties of four sulfated galactomannans were comparatively investigated and analyzed based on our earlier reports of sulfated fenugreek gum, guar gum and locust bean gum. A conclusion was drown that higher galactose branch could enhance steric hindrance, which was inferred as one of the significant factors for the derivatization efficiency, thus affecting the DS, M and conformational transition of sulfated galactomannans. This study will provide valuable information for further research on the comparison of bioactivities and medical application of galactomannans family.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.031DOI Listing
May 2020

Effect and mechanisms of sacral nerve stimulation on visceral hypersensitivity mediated by nerve growth factor.

J Cell Mol Med 2019 12 22;23(12):8019-8024. Epub 2019 Oct 22.

Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

To investigate the efficacy of sacral nerve stimulation (SNS) on nerve growth factor (NGF) mediated visceral sensitivity in normal rat and visceral hypersensitivity model rats. 120 male newborn rats were randomly divided into 6 groups: group A was normal model group; group B ~ F were all sensitized with acetic acid enema and grouped again. Group c2 was given NGF antagonist, d2 group was given NGF agonist, e2 group was given PI3K inhibitor, and f2 group was given PLC-γ inhibitor. After treatment, the expression of NGF, TrKA, PI3K, AKT, PLC-γ, NF-κB, TRPV1, pTRPV1 and intracellular Ca content were detected. The expression of protein TRPV1 and pTRPV1 was increased, and Ca was increased in the visceral hypersensitive group. NGF, TrKA in NGF antagonist group, PI3K, AKT, NF-κB in PI3K inhibitor group, PLC-γ in PLC-γ inhibitor group were all almost not expressed. The relative expression of NGF, TrKA, PI3K, AKT, PLC-γ and NF-κB in NGF antagonist group was lower than that in visceral hypersensitivity group and NGF activator group (P < .01). The relative expression of NGF, TrKA, PI3K and AKT mRNA in NGF antagonist group was lower than that in the normal model group (P < .01). There was no significant difference in the relative expression of PLC-γ and NF-κB mRNA (P > .05). The expression level of MAPK, ERK1 and ERK2 in visceral hypersensitivity group was higher than that in PI3K inhibitor group and PLC-γ inhibitor group. The normal group Ca curve was flat, and the NGF agonist group had the highest Ca curve peak. Calcium concentration in visceral hypersensitivity group was higher than that in PI3K inhibitor group and that in PLC-γ inhibitor group was higher than that in NGF antagonist group. The binding of TrkA receptor to NGF activates the MAPK/ERK pathway, the PI3K/Akt pathway and the PLC-γ pathway, causing changes in the fluidity of intracellular and extracellular Ca , resulting in increased sensitivity of visceral tissues and organs.
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http://dx.doi.org/10.1111/jcmm.14660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850964PMC
December 2019

[Non-cemented modular prosthetic reconstruction for bone defect after tumor resection in lower extremities].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Sep;33(9):1108-1115

Department of Orthopedic Oncology Surgery, Beijing Jishuitan Hospital, Beijing, 100035,

Objective: To report the preliminary clinical results and analyze the prognostic factors of prosthetic failures with non-cemented modular prosthetic reconstruction after tumor resection in lower extremities.

Methods: A clinical data of 150 patients with lower extremity tumors treated with MEGASYSTEM-C non-cemented modular prosthetic reconstruction between October 2011 and September 2016 was retrospectively analyzed. There were 88 males and 62 females, aged from 12 to 81 years, with a median age of 24 years. According to World Health Organization (WHO) classification of bone tumors, 120 cases were primary malignant tumors, 27 cases were intermediate tumors, and 3 cases were metastatic tumors. Among them, 134 cases underwent primary operation and 16 cases underwent reoperation after recurrence. Eighty-seven patients with malignant tumors received chemotherapy before and after operation, and no patient received local radiotherapy during perioperative period. Proximal femur was reconstructed in 32 cases, distal femur in 83 cases, and proximal tibia in 35 cases. The postoperative follow-up time, the results of oncology (survival status and tumor recurrence), and prosthesis failure (prosthesis survival rate, reasons for failure, treatment plan after failure) were recorded. The reason of the prosthesis failure was classified into 5 types according to the classification defined by Henderson . Kaplan-Meier survival analysis and Log-Rank test were used to analyze patient and prosthesis survival. Lower extremity function was assessed by using the Musculoskeletal Tumor Society (MSTS) scoring system and MSTS scores were compared for patients with different reconstruction sites.

Results: All patients were followed up 5-84 months, the median follow-up time was 39 months. During the follow-up period, there were 116 cases of tumor-free survival, 10 cases of tumor-bearing survival, and 24 died of lung metastasis or multiple metastases. The 3-year and 5-year survival rates of 120 patients with primary malignant tumors were 83.1% and 76.6%. There was no significant difference in survival rate between different reconstruction sites ( =0.851). Seven cases (4.7%) had local recurrence at 7-21 months after operation. The 3-year and 5-year survival rates of the prosthesis in 150 patients were 94.4% and 92.5%. There was no significant difference in survival rate between different reconstruction sites ( =0.765). There were 26 failures in 24 patients (16.0%) during the follow-up period. There were 9 cases of type 1 failure, 1 case of type 2 failure, 3 cases of type 3 failure, 5 cases of type 4 failure, and 8 cases of type 5 failure. At last follow-up, 120 of the 126 patients survived without prosthetic failure. Except that the influence of different parts of prosthesis on the incidence of type 4 failure ( =0.029), the influence of chemotherapy on the incidence of type 5 failure ( =0.002) were significant, the influence of other types of failure on different reconstructed parts of prosthesis, initial operation, and perioperative chemotherapy had no significant difference ( >0.05). There were 5 cases of amputation (4 cases of type 5 failure, 1 case of type 4 failure), 3 cases of prosthesis removal (1 case of type 2 failure, 1 case of type 3 failure, 1 case of type 4 failure), 3 cases of revision while keeping the original prosthesis (2 cases of type 1 failure, 1 case of type 5 failure). The overall MSTS score was 24±3. The MSTS scores were 24±3, 25±3, and 23±3 in patients whose reconstruction sites located in proximal femur, distal femur, and proximal tibia, respectively, showing no significant difference ( =3.014, =0.052).

Conclusion: The short-term follow-up showed a lower incidence of complications and good function for MEGASYSTEM-C non-cement modular prosthesis system in treatment of bone defects after lower limb tumor resection. The main factors affecting the early survival of prosthesis were tumor progression and infection.
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http://dx.doi.org/10.7507/1002-1892.201904057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355860PMC
September 2019

A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8 T-cell response and effective tumor control.

Nat Commun 2019 08 28;10(1):3874. Epub 2019 Aug 28.

Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies.
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http://dx.doi.org/10.1038/s41467-019-11782-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713724PMC
August 2019

Epidemiology of Chemotherapy-Induced Anemia in Patients with Non-Hodgkin Lymphoma.

Perm J 2019 27;23. Epub 2019 Jun 27.

Department of Research and Evaluation, Pasadena, CA.

Introduction: Anemia is a common adverse effect of myelosuppressive chemotherapy, and the development of chemotherapy-induced anemia (CIA) is more common in patients with hematologic malignant tumors.

Objective: To assess the incidence and treatment pattern of CIA in patients diagnosed with non-Hodgkin lymphoma (NHL) from a large managed care organization in California.

Methods: Patients diagnosed with NHL between 2010 and 2012 were studied to provide an updated picture of CIA in current hematology-oncology practice. Trends in anemia treatment patterns were examined from 2000 to 2013. All data were collected from Kaiser Permanente Southern California electronic health records.

Results: Of 699 chemotherapy-treated patients with NHL diagnosed between 2010 and 2012, 36.9% and 11.6% developed moderate (hemoglobin < 10 g/dL) and severe (hemoglobin < 8 g/dL) CIA during chemotherapy, respectively. Proportions of moderate CIA events treated with erythropoiesis-stimulating agents (ESAs) decreased from 2000 to 2013: 34% in phase 1 (January 1, 2000, to December 31, 2006), 22% in phase 2 (January 1, 2007, to March 24, 2010), and 6% in phase 3 (March 25, 2010, to June 30, 2013). An increasing trend of red blood cell transfusion was observed: 12% in phase 1, 22% in phase 2, and 27% in phase 3. Similar calendar trends were observed for management of severe CIA events.

Discussion: In contrast to previous European reports, we note a higher incidence of CIA in patients with NHL in this US community practice setting.

Conclusion: Moderate to severe CIA is common in patients with NHL receiving chemotherapy. Multiple ESA-related policy changes occurred from 2000 to 2013. A large proportion of CIA episodes were currently not treated with ESA, and transfusions have become more common. Further studies are needed to determine associations between CIA symptom burden and CIA treatment as they relate to patient outcomes and quality of life.
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http://dx.doi.org/10.7812/TPP/18-252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636493PMC
April 2020

Perioperative rh-endostatin with chemotherapy improves the survival of conventional osteosarcoma patients: a prospective non-randomized controlled study.

Cancer Biol Med 2019 Feb;16(1):166-172

Department of Orthopedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing 100035, China.

Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival (DMFS) and overall survival (OS) in patients newly diagnosed with non-metastatic conventional osteosarcoma.

Methods: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female, with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 years. The control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 months.

Results: The 5-year DMFS of the control group (61%) was significantly lower than that of the rh-endostatin group (79%) ( = 0.013). The 5-year OS of the control group (74%) was significantly lower than that of the rh-endostatin treatment group (87%) ( = 0.029). No difference in adverse drug reactions was found between these 2 groups.

Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528451PMC
February 2019

Comparative effect of black, green, oolong, and white tea intake on weight gain and bile acid metabolism.

Nutrition 2019 09 1;65:208-215. Epub 2019 Mar 1.

Gaikwad Steroidomics Laboratory, Davis, California, USA. Electronic address:

Objective: The beneficial effects of tea on health, including obesity, are well known. However, the comparative effects of black, green, white, and oolong teas, which are prepared from the same fresh leaves, on weight gain and the potential mechanisms involved are not yet fully understood. Bile acids (BAs) are shown to be powerful regulators of metabolism; however, to our knowledge, no studies have investigated the effect of tea on BA metabolism. The aim of this study was to investigate the modulatory effects that green, black, white, and oolong teas that were prepared from the same raw tea leaves have on the plasma BA profile.

Methods: Female rats were dosed with the aforementioned tea types as their sole source of drinking fluid for 28 d. We then investigated their weight and effect on BA metabolic profile using advanced ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS)-based metabolomics.

Results: The UPLC-MS/MS analysis of the plasma show that the levels of murocholic acid, glycochenodeoxycholic acid, glycocholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid, tauromuricholic acid, and taurocholic acid were increased; whereas levels of taurolithocholic acid and isolithocholic acid were decreased after drinking green, oolong, and white tea types compared with control. Surprisingly, oolong tea significantly influenced reduction in relative weight compared with control, black, and green tea; whereas black, green, and white teas had no effects on weight compared with control.

Conclusions: Green, black, oolong, and white teas altered the BA metabolism. This change in BA metabolism could be associated with the health benefit effects of tea. Oolong tea was most effective in reducing weight.
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http://dx.doi.org/10.1016/j.nut.2019.02.006DOI Listing
September 2019
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