Objective:To establish a standardized code database of adverse drug reactions (ADRs) terms related to linezolid and analyze the common ADRs of linezolid.Methods:Linezolid drug labels, websites (including Side Effect Resource, and the official websites of US Food and Drug Administration, European Medicines Agency and National Medical Products Administration) and scientific literature database (including CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases) were systematically searched, and ADR terms about linezolid were collected. ADR terms were mapped to the international classification of diseases-10 (ICD-10) code to establish a linezolid adverse reaction database.Results:A total of 117 ADR terms about linezolid were collected and 91 ICD-10 codes were obtained after being mapped to ICD-10. A standardized database was constructed and successfully embedded into the ADR spontaneous reporting system as a specific drug submodule. The gastrointestinal system, skin and subcutaneous tissue system, various nervous systems, blood and lymphatic systems were the most common system organs involved in linezolid-related ADRs under the 91 ICD-10 codes. Among them, ADRs under the gastrointestinal system codes K14.302 (black hairy tongue) and K52.104 (drug-induced gastroenteritis and colitis), the skin and subcutaneous tissue system code L27.005 (drug-induced dermatitis), various nervous system codes G90.800 (other disorders of autonomic nervous system), G62.001 (drug-induced polyneuropathy) and G44.400 (drug-induced headache, not elsewhere classified), the blood and lymphatic system codes D69.502 (drug- induced thrombocytopenia) and D70.x02 (drug-induced granulocytopenia), the metabolic and nutritional codes E87.204 (lactic acidosis), as well as the endocrine system code E16.000 (drug-induced hypoglycaemia without coma) had been reported frequently in the scientific literature. In addition, there were 14 ADR terms related to linezolid under 13 ICD-10 codes not recorded in the drug instructions.Conclusions:It is feasible to use ICD-10 code to standardize ADR terms related to linezolid and establish a database. Common ADRs of linezolid include thrombocytopenia, lactic acidosis, neutropenia, black hairy tongue, gastroenteritis/colitis, hypoglycemia, rash, serotonin syndrome, peripheral neuropathy and headache, which should be paid attention to and researched furtherly.

Objective:To establish a standardized code database of adverse drug reactions (ADRs) terms related to linezolid and analyze the common ADRs of linezolid.Methods:Linezolid drug labels, websites (including Side Effect Resource, and the official websites of US Food and Drug Administration, European Medicines Agency and National Medical Products Administration) and scientific literature database (including CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases) were systematically searched, and ADR terms about linezolid were collected. ADR terms were mapped to the international classification of diseases-10 (ICD-10) code to establish a linezolid adverse reaction database.Results:A total of 117 ADR terms about linezolid were collected and 91 ICD-10 codes were obtained after being mapped to ICD-10. A standardized database was constructed and successfully embedded into the ADR spontaneous reporting system as a specific drug submodule. The gastrointestinal system, skin and subcutaneous tissue system, various nervous systems, blood and lymphatic systems were the most common system organs involved in linezolid-related ADRs under the 91 ICD-10 codes. Among them, ADRs under the gastrointestinal system codes K14.302 (black hairy tongue) and K52.104 (drug-induced gastroenteritis and colitis), the skin and subcutaneous tissue system code L27.005 (drug-induced dermatitis), various nervous system codes G90.800 (other disorders of autonomic nervous system), G62.001 (drug-induced polyneuropathy) and G44.400 (drug-induced headache, not elsewhere classified), the blood and lymphatic system codes D69.502 (drug- induced thrombocytopenia) and D70.x02 (drug-induced granulocytopenia), the metabolic and nutritional codes E87.204 (lactic acidosis), as well as the endocrine system code E16.000 (drug-induced hypoglycaemia without coma) had been reported frequently in the scientific literature. In addition, there were 14 ADR terms related to linezolid under 13 ICD-10 codes not recorded in the drug instructions.Conclusions:It is feasible to use ICD-10 code to standardize ADR terms related to linezolid and establish a database. Common ADRs of linezolid include thrombocytopenia, lactic acidosis, neutropenia, black hairy tongue, gastroenteritis/colitis, hypoglycemia, rash, serotonin syndrome, peripheral neuropathy and headache, which should be paid attention to and researched furtherly.

Objective:To explore the research hotspots and effective promotion paths of post market surveillance and supervise of medical consumables with non-active medical devices.Methods:Data mining methods were used to collect related journal literatures and documents from the websites of China regulatory institutions and the China National Knowledge Infrastructure(CNKI),order sub item data of medical device adverse event reports,extract the MeSH element words of literatures and documents,perform bibliometric analysis and visual display.Results:The number of medical devices adverse event reports in China has been increasing year by year,reaching 694 866 in 2022,in the four statistical years from 2019 to 2022,the number of reports on non-active medical devices and IVD reagents also showed a parallel increasing trend,accounting for about 65.00% of the total number of adverse event reports on medical devices in the year.The bibliometric analysis of journal literature shows that research in this field has received varying degrees of participation from regulatory institutions,universities,medical institutions,and enterprises.Regulatory institutions have contributed 46 articles,accounting for 56.79% of the total number of articles,followed by 28 articles from universities.The co-occurrence analysis shows that hot topic is focused in 5 clusters:quality management,risk management,international experiences discussion and adverse event surveillance and re-evaluation and real-world research.China regulatory institutions attach great importance to post market surveillance and supervise,and have issued more than 20 relevant documents since 2006,focusing on specific topics and gradually deepening around safety and effectiveness.Conclusion:The post market surveillance and supervise of medical devices,especially medical consumables based on non-active medical devices,need to be promoted synchronously in three dimensions:regulatory institutions,medical institutions,and enterprises.Universities,research institutes,and industry organizations should work in coordinating to strengthen the collection,identification,and active surveillance of risk signals based on adverse event surveillance,safety evaluation based on risk management,and conducting real-world research,research and develop risk control and corrective and preventive measures.

Objective:To understand the clinical characteristics of hemophagocytic lymphohistiocytosis (HLH) induced by immune checkpoint inhibitors (ICIs).Methods:Relevant databases at home and abroad (up to February 15, 2024) were searched and case reports of HLH induced by ICIs were collected. Relevant information of patients (gender, age, primary disease), usage and dosage of ICI, combined drugs, occurrence time, clinical manifestations, management, and outcomes of HLH were extracted and analyzed descriptively and statistically.Results:A total of 37 case reports were enrolled in the analysis, involving 44 patients. Of them, 26 patients were male and 18 were female. The age ranged from 2 to 86 years, with a median age of 67 years. The primary diseases included melanoma in 14 patients, lung cancer in 12 patients, kidney cancer in 4 patients, oral squamous cell carcinoma and acute myeloid leukemia in 2 patients each, and other 10 malignant tumors in one patient each. A total of 8 ICIs were used, including pembrolizumab in 17 patients, nivolumab in 10 patients, nivolumab combined with ipilimumab in 8 patients, atezolizumab, camrelizumab, and ipilimumab in 2 patients each, and toripalimab, tislelizumab, and avelumab in 1 patient each. Among them, 33 patients received single ICI immunotherapy, 6 patients received immunotherapy combined with targeted therapy, and 5 patients received immunotherapy combined with chemotherapy. Twenty-two patients had medication dosage records, and the administration method was all intravenous infusion. The shortest time for HLH occurrence was 1 day after medication, the longest was 8 months, and the median time was 5 days. The clinical manifestations included recurrent fever, fatigue, loss of appetite, etc. Laboratory and auxiliary examinations showed decreased blood cells, elevated ferritin, increased hemophagocytic cells, and spleen enlargement. After the diagnosis of HLH, 40 cases discontinued the drug, 1 did not stop, and 3 were unknown. Forty-two patients received symptomatic treatments, of which 18 patients returned to normal, 17 patients were improved, 1 patient was unknown, and 6 patients died. Two patients who did not receive intervention died.Conclusions:The main clinical symptoms of ICI-related HLH are fever, fatigue, weakness, loss of appetite, and hemophagocytosis. Withdrawal and symptomatic treatments can effectively improve the symptoms of patients, but HLH has a higher risk of death.

Objective:To understand the clinical characteristics of hemophagocytic lymphohistiocytosis (HLH) induced by immune checkpoint inhibitors (ICIs).Methods:Relevant databases at home and abroad (up to February 15, 2024) were searched and case reports of HLH induced by ICIs were collected. Relevant information of patients (gender, age, primary disease), usage and dosage of ICI, combined drugs, occurrence time, clinical manifestations, management, and outcomes of HLH were extracted and analyzed descriptively and statistically.Results:A total of 37 case reports were enrolled in the analysis, involving 44 patients. Of them, 26 patients were male and 18 were female. The age ranged from 2 to 86 years, with a median age of 67 years. The primary diseases included melanoma in 14 patients, lung cancer in 12 patients, kidney cancer in 4 patients, oral squamous cell carcinoma and acute myeloid leukemia in 2 patients each, and other 10 malignant tumors in one patient each. A total of 8 ICIs were used, including pembrolizumab in 17 patients, nivolumab in 10 patients, nivolumab combined with ipilimumab in 8 patients, atezolizumab, camrelizumab, and ipilimumab in 2 patients each, and toripalimab, tislelizumab, and avelumab in 1 patient each. Among them, 33 patients received single ICI immunotherapy, 6 patients received immunotherapy combined with targeted therapy, and 5 patients received immunotherapy combined with chemotherapy. Twenty-two patients had medication dosage records, and the administration method was all intravenous infusion. The shortest time for HLH occurrence was 1 day after medication, the longest was 8 months, and the median time was 5 days. The clinical manifestations included recurrent fever, fatigue, loss of appetite, etc. Laboratory and auxiliary examinations showed decreased blood cells, elevated ferritin, increased hemophagocytic cells, and spleen enlargement. After the diagnosis of HLH, 40 cases discontinued the drug, 1 did not stop, and 3 were unknown. Forty-two patients received symptomatic treatments, of which 18 patients returned to normal, 17 patients were improved, 1 patient was unknown, and 6 patients died. Two patients who did not receive intervention died.Conclusions:The main clinical symptoms of ICI-related HLH are fever, fatigue, weakness, loss of appetite, and hemophagocytosis. Withdrawal and symptomatic treatments can effectively improve the symptoms of patients, but HLH has a higher risk of death.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4⁺ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease. METHODS: From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI. CONCLUSIONS In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.
Humans ; Leukocytes, Mononuclear ; Lupus Erythematosus, Systemic/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; DNA Repair ; RNA, Messenger/metabolism*

Objective: To detect the values of CT texture features in the preoperative prediction of Fuhrman grade of clear cell renal cell carcinoma (ccRCC). Methods: The CT data of 206 patients with ccRCC admitted to the Third Affiliated Hospital of Soochow University from January 2011 to December 2016 were retrospectively analyzed, and the ccRCC cases were graded using Fuhrman grading system, including 38 cases of Grade Ⅰ, 107 cases of Grade Ⅱ, 50 cases of Grade Ⅲ and 11 cases of Grade Ⅳ. All subjects undergone plain and enhancement CT scans. There were two methods used for the extraction of texture features, including histogram (2 features: Kurtosis and Skewness) and gray-level co-occurrence matrix (6 features: Contrast, Correlation, Energy, Entropy, Homogeneity and Variance). Each texture feature during Grade Ⅰ to Ⅳ was compared using a one-way analysis of variance following the log-ratio transformation, and a Newman-Keuls test was performed for all pairwise comparisons. An independent sample t test was used to find the differences of each texture feature between low (Grade Ⅰ+Ⅱ) and high grade (Grade Ⅲ+Ⅳ) ccRCC. A Spearman Rank test was performed to quantify the correlation of each texture feature with Fuhrman grade in ccRCC. Receiver operating characteristic curve (ROC) was employed to compare the diagnostic performance of the texture features to differentiate the low grade from high grade ccRCC. Results: Six texture features, including Contrast, Correlation, Entropy, Homogeneity, Variance and Kurtosis, were different during Grade Ⅰ to Ⅳ (all P<0.05) with the exception of the two features of Energy and Skewness (all P>0.05). Furthermore, five textures, such as Correlation, Entropy, Homogeneity, Variance and Kurtosis, were not significantly different between Grade Ⅲ and Ⅳ ccRCC. There was no clinical application value for the features of Correlation, Energy, Entropy, Variance and Skewness with the absolute coefficients of<0.3, in contrast, the correlation coefficients were -0.54, 0.39 and 0.32 for the features of Contrast, Homogeneity and Kurtosis, respectively (all P<0.05). Compared with that in the low grade ccRCC, the values of Contrast and Variance reduced in the high grade ccRCC (all P<0.05), while the values of Kurtosis, Correlation and Homogeneity increased significantly in the high grade ccRCC (all P<0.05), and no difference was found for the features of Skewness, Energy and Entropy between the low and high grade ccRCC (all P>0.05). When those features were used to differentiate the high from low grade ccRCC, the Contrast exhibited the biggest area under ROC of 0.806 (P<0.05), followed by the Correlation of 0.641, Homogeneity of 0.687, Kurtosis of 0.668 and Variance of 0.659. Conclusion CT texture features can preoperatively predict the Fuhrman grade of ccRCC, and the Contrast will likely be the potential imaging biomarker for the clinical application.

Objective To probe the feasibility of susceptibility weighted imaging (SWI) for evaluation of renal blood oxygenation level of healthy volunteers after water loading.Methods SWI of 11 healthy volunteers,acquired before (group 1) and after water loading (group 2),were assessed retrospectively by two radiologists with more than 10 years abdominal work experience independently.In those images of the same section plane derived from two groups,the phase values in cortex ((φ)cor) and medulla ((φ)med),difference between the same vein and surrounding tissue on phase map (△(φ)) were measured using SPIN software package,and the oxygen extraction fraction changes (△OEF) was calculated.The (φ)cor,(φ)med and △(φ) between two groups were compared by paired t test.And the intraclass correlation coefficient (ICC)was used to evaluate the consistency between two radiologists.Results For the radiologist 1,the (φ)cor,(φ)med and △(φ) were (0.046 ±0.019),(-0.014 ±0.003) and (1.3 ±0.4) rad in group 1,and were (0.047 ±0.014),(-0.012 ±0.005) and (1.1 ±0.4) rad in group 2 respectively,and no significant change was found in (φ)cor and (φ)med after water loading (t =-0.589 and-0.206,P ＞ 0.05 in all),except of in △(φ) (t =2.400,P ＜ 0.01).For the radiologist 2,the (φ)cor,(φ)med and △△(φ) were (0.049 ± 0.011),(-0.012 ± 0.004)and (1.5 ±0.4) rad in Group 1,and were (0.046 ±0.017),(-0.011 ±0.003) and (1.3 ±0.2) rad in group 2 respectively,there was no significant change in (φ)cor and (φ)med after water loading (t =0.590 and -0.974,P ＞ 0.05 in all),except of in △(φ) (t =2.760,P ＜ 0.05).Between two radiologists,the ICC of (φ)cor,(φ)med and △(φ) were 0.623,0.472 and 0.328 in group 1 and 0.599,0.442 and 0.445 in group 2 respectively.△OEF decreased about (-4.2 ± 2.3) c％ and (-4.3 ± 2.8) c％ measured by two radiologists respectively,and the consistency is good between two radiologists (ICC =0.784).Conclusion SWI provides a novel method to assess indirectly the oxygenation level of kidney,△OEF is an indicator with suitable reliability.

ObjectiveTo investigate the influence of cobalt chloride ( CoCl2 )-mimetic hypoxia on theproliferation,apoptosis and migration of human pancreatic cancer cell fine PANC1.MethodsPANC1 cells were treated with 0(control),100,200,400,800 μmol/L CoCl2 respectively for 24 h.Real-time RT-PCR and Western blot were used to determine hypoxia induced factor ( HIF)-1o mRNA and protein expression respectively,and cell counting kit-8(CCK-8) assays,flow cytometry and cell scratch test were used to examine the proliferation,apoptosis and migration of PANC1 cells,respectively.ResultsIn the control group and 100,200,400 and 800 μmol/L CoCl-2 groups,the expressions of HIF-1t mRNA were 1,1.08 ±0.12,1.12 ± 0.09,1.04±0.11,0.66 ±0.07,and the expressions of VEGF mRNA were 1,2.69±0.35,4.81 ±0.54,2.19 ± 0.21,0.79 ± 0.08,while the expressions of HIF-1 α protein were 0.23 ± 0.03,0.36 ± 0.04,1.15 ± 0.11,1.08 ± 0.09,0.44 ± 0.04; and the expressions of VEGF protein were 0.14 ± 0.02,0.12 ± 0.01,0.95 ±0.09,0.87 ±0.09,0.55 ±0.06; and cell viability rates were 100％,(98.43 ±2.88)％,(76.15 ± 0.70)％,(53.87 ±0.77)％,(35.23 ±0.67)％ ; while cell apoptotic rates were (5.2 ±1.12)％,(5.74 ± 1.07)％,(6.82 ± 1.85)％,(12.09 ±3.53)％,(31.88 ±6.95)％ ; the cell migration distance of PANC1 cells were (43.24 ±3.67)％,(59.46 ±5.39)％,(80.56 ±8.05)％,(63.89 ±5.96)％,(9.09 ± 1.59 ) ％.Compared with those of control group,the expressions of VEGF mRNA,VEGF and HIF-1 α protein,cell migration distance showed a two-way variation ( ascending first and descending later) (P ＜0.05 ),and the expression of HIF-1α mRNA and cell proliferation rate was decreased in a dose-dependent manner,while the cell apoptosis was increased in a dose-dependent manner.Conclusions CoCl2 significantly inhibits the proliferation and promotes apoptosis of PANC1 cells at certain level.CoCl2 has a two-way effect on the migration of PANC1 cells,and it may be related to the direct injury of high concentration of CoCl2 on cells.

Objective To increase the awareness of autoimmune pancreatitis (AIP) and correct diagnosis rate of AIP by investigating radiologic characteristic of AIP and small pancreatic cancers.Methods The clinical data and radiologic imaging of 24 AIP patients who met the Asia diagnostic criteria of AIP in 2008 and 25 cases of pathologically condirmed small pancreatic cancer were retrospectively reviewed.All imaging findings were reviewed,especially on the shape,enhancement patterns of mass,pancreatic ducts,peripancreatic and extra-pancreatic manifestations. Chi-square test and Fisher test were used for statistical analysis.ResultsThe imaging signs,including location of masses,distal pancreatic atrophy,enhancing mass during portal phase,truncated duct sign of pancreatic duct,capsule-like rim and renal involvement,was significantly different between AIP and small pancreatic cancer ( x2 =9.010,10.506,15.488,8.688,6.292 and 4.966 respectively,P ＜0.05 ).But only two signs,distal pancreatic atrophy and enhancing mass during arterial and portal phase,were statistically different between local AIP and small pancreatic cancer (P ＜0.05).ConclusionsThe typical imaging features of diffuse AIP is distinct and helpful for the differential diagnosis of AIP from small pancreatic carcinoma,but there is limited value in the differential diagnosis between local AIP and small pancreatic cancer.