[Efficacy and safety analysis of eltrombopag and recombinant human thrombopoietin combined with immunosuppressive therapy for severe aplastic anemia].

Objective: To evaluate the efficacy and safety of combination therapy of eltrombopag, recombinant human thrombopoietin (rhTPO) , and standard immunosuppressive therapy (IST) for severe aplastic anemia (SAA) . Methods: A total of 16 cases with SAA treated with IST combined with eltrombopag and rhTPO were retrospectively analyzed. Results: At 3 months, the total response rate was 81.3%, and the complete hematological response rate was 37.5%. At 6 months, the total response rate was 87.5%, and the complete hematological response rate was 50.0%. The median time of platelet transfusion independence was 35 (16-78) days, the median time of red blood cell transfusion independence was 47.5 (15-105) days, the median platelet transfusion was 5.5 (3-20) U, and the median red blood cell transfusion was 6.5 (2-16) U. Conclusion: The combination of eltrombopag and rhTPO can improve the hematological response rate of IST for SAA and the quality of hematological remission with minimal toxic effects.

[Clinical effect analysis of 146 cases of ipsilateral simultaneous pancreas and kidney transplantation].

Objective: To investigate the clinical effect of ipsilateral simultaneous pancreas and kidney transplantation (SPK). Methods: A total of 146 cases of SPK surgeries completed in the Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020 were selected to summarize the outcome, curative effect and complications of the operation. Results: The patients were followed up for 1 to 45 months. Good clinical results were obtained in 146 patients. Renal function indicators suggest that on the 7th day after operation, the serum creatinine returned to normal level [142.4 (108.6, 213.4)µmol/L]. The index of pancreatic function decreased to the normal level as expected. The level of blood amylase was 160.5(109.3, 249.8) U/L within 7 days after operation, and then decreased. The trend of urinary amylase was similar to that of blood amylase, which was 240(121.0, 370.0) U/L 7 days after operation, and glycosylated hemoglobin decreased to the normal level (5.8%±1.4%) 1 month after operation. The main medical complications were infection including pulmonary infection (26.03%, 38/146), urinary tract infection (26.03%,38/146), and abdominal infection (4.79%,7/146), acute rejection including renal graft rejection (5.8%,8/146), pancreas/duodenum rejection (18.49%,27/146), and renal graft combined pancreatic graft rejeciton (6.85%,10/146), as well as gastrointestinal bleeding (30.82%,45/146), of which 5 cases were severe bleeding (3.42%, 5/146). The main surgical complications were poor incision healing (10.27%, 15/146), serious surgical complications including arteriovenous thrombosis of the transplanted pancreas (2.05%, 3/146) and intestinal leakage (0.68%,1/146). The 1-year and 3-year patient, renal and pancreatic survival rates were both 92.5%, 91.5% and 89.5%, respectively, and despite the death, the 1-year, 3-year transplanted kidney survival rate was both 99.3%, and 95% for the the 1-year, 3-year pancreas survival rate. Conclusion: Strict preoperative evaluation of the function of large organs, reasonable surgical methods, perioperative anticoagulation, and prompt diagnosis of complications can achieve good clinical results for patients with SPK.

[The 477th case: muscular spasms, alopecia, diarrhea].

Diarrhea is a common digestive symptom. Here, we reported a case of young patient admitted with diarrhea caused by lead poisoning and cytomegalovirus infection. Through informative medical history and multi-disciplinary team discussion, Satoyoshi syndrome was finally diagnosed.

[Clinical characteristics of metastasis-induced acute pancreatitis in patients with lung cancer].

Objective: To analyze the clinical features and prognosis of lung cancer patients with metastasis-induced acute pancreatitis (MIAP), and to provide clues for early diagnosis. Methods: The characteristics and prognosis of 8 patients with MIAP in lung cancer admitted to Peking Union Medical College Hospital from January 2002 to September 2019 were retrospectively analyzed and were compared with non-tumor-induced AP. Results: Sevencases(7/8) were Mild AP, one (1/8) was Severe AP. Four patients (4/8) presented with AP as the reporting sign and lung cancer was not diagnosed until (112±36) days after the onset of AP. Clinical manifestations included abdominal pain (8/8), weight loss (4/8), nausea and vomiting (2/8), and jaundice (1/8). Stages of lung cancer were all Ⅳ.Histopathology proved that seven cases (7/8) were small cell lung cancer, and one case (1/8) was poorly differentiated adenocarcinoma. The median survival time was 11 months. Compared with non-tumor-induced AP, lung cancer patients with MIAP were older[(62±9) vs (48±15), P=0.018], the incidence of primary pancreatic duct dilatation (37.5% vs 3.1%, P=0.004) and abdominal lymphadenopathy (37.5% vs 6.3%, P=0.017) were higher; the level of hemoglobin [105.3±15.6) g/L vs (147.9±24.8) g/L, P<0.001] and hematocrit [(31.4±5.3) vs (42.5±6.1), P<0.001] were lower. Conclusions: Patientswith MIAP in lung cancer had poor outcome and unspecific symptoms. Old age, anemia, main pancreatic duct dilatation and abdominal lymphadenopathy are diagnostic clues that merit clinical attention.

[A questionnaire survey for gout management in physicians in Beijing].

Objective: To provide helpful continued medical education (CME) for physicians and improve gout treatment, we conducted a questionnaire survey to investigate physicians' knowledge in nine districts of Beijing. Methods: A questionnaire survey including ten gout-related questions was conducted among 298 physicians in Beijing. Demographic data and previous gout CME experience were collected. Chi-square test or Student's t test, univariate analysis and logistic regression analysis were used to evaluate the relevant factors of physicians' knowledge level. Results: A total of 250 valid copies were collected including 127 from community service centers (CSC), 123 from tertiary hospitals. The correct answer rate of gout etiology, pathogenesis and attack symptoms were over 70% in both groups. 45.5% (56/123) CSC doctors and 57.4% (66/115) tertiary doctors answered right drugs to control acute gout attack (P=0.067). Only 42.3% (52/123) in CSC and 53.4% (63/118) in hospitals chose allopurinol as a urate-lowering drug (ULT), while 46.3% (57/123) and 32.2% (38/118) doctors considered colchicine as a ULT drug (P=0.084) respectively. Near half doctors considered that gout patients should take long-term ULT [40.5% (51/126) vs. 57.6%(68/118)respectively, P=0.007]. Univariate analysis showed that CME training could improve gout-related knowledge in CRC doctors. Conclusion: Most CSC doctors generally understand basic knowledge of gout, while confusion of treatment is still significant. CME especially including standard gout treatment should be performed by doctors in tertiary hospitals.

[Clinical application of renal autotransplantation in complex urological diseases].

Objective: To summarize the experience of renal autotransplantation for severe iatrogenic proximal ureteral damage and renal artery aneurysms in eight patients and to explore the clinical application value of renal autotransplantation. Methods: Two patients of renal artery aneurysms and six patients of severe iatrogenic proximal ureteral damage between January 2010 and March 2018 in our center were retrospectively reviewed. Results: The procedures of eight cases were successful, with immediate return of renal function in the patients. The warm ischemia time was (3±1) minutes, the total operation time was (340±164) min, and the estimated blood loss was (180±60) ml, respectively. For renal artery anastomosis, six patients of severe iatrogenic proximal ureteral damage received end-to-end anastomosis between the internal iliac artery and renal artery, and two patients of renal artery aneurysms were treated with renal artery and internal iliac artery for reconstruction, then end-to-side anastomosis to recipien external iliac artery. A direct ureterovesical anastomosis was performed in seven patients, one patient was received pyeloureteroplasty. No serious complications of blood vessel and ureter were found during perioperative and long-term follow-up. All cases follow-up hitherto have normal renal function and blood pressure. Conclusions: Renal autotransplantation can be appropriate for patients with proximal ureteral loss and complex hilar renal artery aneurysms. In addition, it is able to protect renal functions to the most extent and provides a surgical alterative for complex renal diseases.

[Efficacy and safety of domestic dasatinib as second-line treatment for chronic myeloid leukemia patients in the chronic phase].

Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion: Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.

[The expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia and its prognostic significance].

Objective: To detect the expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia (B-ALL) in newly diagnosed cases, and to investigate the relationship between CRLF2 and the general clinical characteristics, efficacy and prognosis. Methods: 103 cases of newly diagnosed adult B-ALL patients were investigated from Apr 2016 to Dec 2017 in the Department of Hematology, Henan Cancer Hospital. Bone marrow samples was used to detect the expression of CRLF2 in leukemic cells. The expression of CRLF2 ≥20% was defined as CRLF2-high group and <20% was defined as CRLF2-low group. The clinical characteristics and prognosis of the two groups were compared. Results: The Median overall survival (OS) and disease free survial (DFS) in CRLF2-high group were 9.0 months and 4.25 months, respectively. CRLF2-low group were 15.5 months and 10.25 months, respectively. There was a statistically significant difference in median OS and DFS between the two groups (P=0.007, P=0.000) . The 18-month OS and DFS in CRLF2-high group were 38.6% and 25.1%, respectively. CRLF2-low group were 57.8% and 42.3%, respectively. Multivariate analysis showed high expression of CRLF2 was an independent risk factor for OS (HR=2.991, 95% CI 1.429-6.261, P=0.004) and DFS (HR=2.374, 95%CI 1.146-4.960, P=0.041) in patients. Conclusion: Patients with high expression of CRLF2 had poor prognosis.

[Synchronous lymphoma and carcinoma-clinical analyses of 17 patients].

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion: The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

[The clinical analysis of frontline nilotinib vs imatinib therapies for newly diagnosed chronic myeloid leukemia in chronic phase].

Objective: To compare the clinical efficacy and safety of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase(CML-CP). Methods: Until December 31st 2016, 18 patients using nilotinib and 83 using imatinib were recruited in our study. The efficacy and safety of two groups were evaluated. Results: A total of 101 patients with CML-CP included 18 receiving nilotinib and 83 imatinib. The optimal response rates at 3, 6, 12 and 18 months in nilotinib and imatinib group were 88.9% (16/18) vs 57.3% (47/82) (P=0.012), 82.4% (14/17) vs 55.7% (44/79) (P=0.041), 9/12 vs 63.9% (39/61) (P=0.460), 6/9 vs 68.9% (31/45) (P=0.896) respectively. The optimal response rates by 3 months in low sokal risk group on nilotinib and imatinib were 9/9 vs 76.5%(26/34) (P=0.107), in intermediate and high sokal risk group were 7/8 vs 45.2%(14/31) (P=0.032). At the end of follow-up, the rate of major molecular response (MMR) in nilotinib group was 72.2%, which was higher than 56.6% in imatinib group (P=0.021). The rate of complete cytogenetic response (CCyR) in nilotinib group was 100%, which was higher than 71.1% in imatinib group (P = 0.002). Progression free survival (PFS) rates in nilotinib and imatinib groups were 94.4% and 98.8% (P=0.019) respectively; whereas event free survival (EFS) rates were 88.9% and 48.2% (P=0.045). The incidence of drug related adverse reactions in nilotinib and imatinib was similar with only minor proportion of grade 3/4 adverse reactions. Conclusions: Nilotinib achieves a deeper molecular response in a shorter time than imatinib in newly diagnosed patients with CML-CP, especially in patients with high risk outcome. Good safety is obtained in both groups so as to ensure a long-term administration and improving prognosis.

[Comparison of adaptation and microstructure of titanium upper complete denture base fabricated by selecting laser melting and electron beam melting].

Objective: To fabricate Ti alloy frameworks for a maxillary complete denture with three-dimensional printing (3DP) technique, such as selective laser melting (SLM) and electron beam melting (EBM), and to evaluate the microstructure of these frameworks and their adaptation to the die stone models. Methods: Thirty pairs of edentulous casts were divided into 3 groups randomly and equally. In each group, one of the three techniques (SLM, EBM, conventional technique) was used to fabricate Ti alloy frameworks. The base-cast sets were transversally sectioned into 3 sections at the distal of canines, mesial of first molars, and the posterior palatal zone. The gap between the metal base and cast was measured in the 3 sections. Stereoscopic microscope was used to measure the gap. Three pieces of specimens of 5 mm diameter were fabricated with Ti alloy by SLM, EBM and the traditional casting technology (as mentioned above). Scanning electron microscope (SEM) was used to evaluate the differences of microstructure among these specimens. Results: The gaps between the metal base and cast were (99.4±17.0), (98.2±26.1), and (99.6± 16.1) µm in conventional method; (99.4 ± 22.8), (83.1 ± 19.3), and (103.3 ± 13.8) µm in SLM technique; (248.3±70.3), (279.1±71.9), and (189.1±31.6) µm in EBM technique. There was no statistical difference in the value of gaps between SLM Ti alloy and conventional method Ti alloy group (P>0.05). There was statistical difference among EBM Ti alloy, conventional method Ti alloy and SLM Ti alloy group (P<0.05). The SLM Ti alloy showed more uniform and compact microstructure than the cast Ti alloy and EBM Ti alloy did. Conclusions: SLM technique showed initial feasibility to manufacture the dental base of complete denture. The mechanical properties and microstructure of the denture frameworks prepared by SLM indicate that these dentures are appropriate for clinical use. EBM technique is inadequate to make a complete denture now.

Detection of high-risk human papillomavirus DNA and immunohistochemical expressions of p16, vimentin, ER, and PR in primary endocervical and endometrial adenocarcinomas.

OBJECTIVE: The aim of this study was to explore a panel of useful markers in differential diagnosis of primary endocervical adenocarcinoma (ECA) and endometrial adenocarcinoma (EMA). Materials anid Methods: Thirty-three ECAs and 31 EMAs were collected and examined for high-risk human papillomavirus (hr-HPV) (16/18) DNA using in situ hybridization, and for p16, vimentin, ER, PR expression using immunohistochemistry (IHC). RESULTS: Detection rate of hr-HPV (16/18) DNA in ECA (72.7%, 24/33) was significantly higher than that in EMA (12.9%, 4/31) (p < 0.01). Twenty-four of 33 (72.7%) cases of ECA, but only five of 31 (16.1%) cases of EMA showed high expression of pl6. Twenty-three of 24 (95.8%) hr-HPV DNA-positive ECA and all four (100.0%) hr-HPV DNA-positive EMA showed high levels of pl6 expression. High expression rates of vimentin (90.3%, 28/31), ER (58.1%, 18/31), and PR (71.0%, 22/31) in EMA were significantly higher than those in ECA, respectively (p < 0.01). CONCLUSION: Detection of hr-HPV DNA combined with immunohistochemical expressions of pl6, vimentin, ER, and PR have important value in differential diagnosis between ECA and EMA.

Comparison of tacrolimus and cyclosporin A in CYP3A5 expressing Chinese de novo kidney transplant recipients: a 2-year prospective study.

AIMS: To assess the efficacy and safety of tacrolimus and cyclosporin A (CsA)-based immunosuppressive regimens in Chinese de novo kidney transplant recipients who are CYP3A5 expressers. METHODS: The CYP3A5 (6986 A>G, rs776746) polymorphism of eligible patients was determined before transplantation. De novo kidney transplant recipients enrolled in this study were assigned to tacrolimus (Tac group) or CsA (CsA group) based therapy. The follow-up period was 2 years. The incidence of acute rejection, patient and graft survival rates, renal allograft function and post-transplant complications were compared. The intra-individual variability (IIV) of Tac and CsA blood concentrations was analysed. Medication costs were also compared. The analysis was conducted on the intention-to-treat principle. RESULTS: A total of 72 CYP3A5 expressers were enrolled, with 36 patients in each group. AR incidence was higher in the Tac group (11.1% vs. 5.6%), but there was no significant difference (p > 0.05). The 2-year patient and graft survival was comparable, and renal function was comparable in the two groups. Notably, the Tac group presented a significantly higher incidence of BK viremia (22.2% vs. 5.6%, p < 0.05) and BK viruria (38.9% vs. 16.7%, p < 0.05) than the CsA group. The CsA IIV at 1 and 3 months post-transplant was significantly lower than the Tac IIV (p < 0.05). The medical costs of both immunosuppressive drugs and management of complications was significantly lower in the CsA group. CONCLUSIONS: Cyclosporin A-based maintenance therapy is safe for Chinese de novo kidney transplant recipients who are CYP3A5 expressers. CsA significantly reduced medication costs and decreased BKV infection, suggesting that it is more beneficial for this specific population.

Seasonal concentrations, contamination levels, and health risk assessment of arsenic and heavy metals in the suspended particulate matter from an urban household environment in a metropolitan city, Beijing, China.

The levels and health risks of arsenic and heavy metals (As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn) in the suspended particulate matter (SPM) collected from an urban household environment in Beijing of China for 12 months were investigated. The mean concentrations of the studied toxic elements were higher and lower than crustal abundance and PM2.5 in the urban outdoors of Beijing. The concentrations of the studied elements displayed significant seasonality. The highest concentrations of the total elements occurred in winter, followed by autumn, while the lowest concentrations were recorded in summer. Based on the calculated values of enrichment factor (EF) and geoaccumulation index (Igeo), the levels for As and Cu were heavily contaminated, while those for Cd, Pb, and Zn were extremely contaminated. As and Pb might pose risks to children and adults via ingestion exposure. The accumulative risks of multi-elements resulted from dermal contact and inhalation exposures were not negligible. More attention should be paid to reducing the non-carcinogenic and carcinogenic health risks posed by the toxic elements bound to urban household SPM particles via ingestion, inhalation, and dermal contact exposure.