To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

An analytical method for 10 mycotoxins in Hippophae Fructus medicinal and edible products was established in this study, and the contamination of their mycotoxins was analyzed. First of all, the mixed reference solution of ten mycotoxins such as aflatoxin, ochratoxin, zearalenone, and dexoynivalenol was selected as the control, and the Hippophae Fructus medicinal and edible products were prepared. Secondly, based on the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) technology, 10 mycotoxins in Hippophae Fructus medicinal and edible products were quantitatively investigated and their content was determined. Finally, the contamination of mycotoxins was analyzed and evaluated. The optimal analysis conditions were determined, and the methodological inspection results showed that the 10 mycotoxins established a good linear relationship(r>0.99). The method had good repeatability, test sample specificity, stability, and instrument precision. The average recovery rates of 10 mycotoxins in Hippophae Fructus medicinal products, edible solids, and edible liquids were 90.31%-109.4%, 87.86%-107.8%, and 85.61%-109.1%, respectively. Relative standard deviation(RSD) values were 0.22%-10%, 0.75%-13%, and 0.84%-8.5%, repsectively. Based on UPLC-MS/MS technology, the simultaneous determination method for the limits of 10 mycotoxins established in this study has fast detection speed, less matrix interference, high sensitivity, and accurate results, which is suitable for the limit examination of 10 mycoto-xins in Hippophae Fructus medicinal and edible products.
Mycotoxins/analysis* ; Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Hippophae ; Limit of Detection ; Chromatography, High Pressure Liquid/methods*

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To explore 3.0T MRI accurate measurement of knee cartilage thickness in healthy youth provides reliable anatomical parameters for quantitative diagnosis of osteoarthritis and accurate osteotomy of joint replacement. METHODS: From January 2013 to December 2013, 30 healthy young volunteers including 14 males and 16 females with an average age of (25.8±2.4) years old ranging from 22 to 33 years were recruited in Changchun, Jilin Province, and a 3.0T MRI scan was performed on the bilateral knee joints of each volunteer. The cartilage thickness was measured on the lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibial plateau (LTP) and medial tibial plateau (MTP). RESULTS: In four regions of the knee joint:LFC, MFC, LTP and MTP, whether young men or women, there was no significant difference in cartilage thickness between the left and right knee joints (P>0.05). There were significant differences in knee cartilage thickness between healthy young men and women (P<0.05). In the same sex group, LFC cartilage thickness was thinner in the middle, thicker in front and rear;MFC cartilage thickness was the thinnest in front and gradually thickening from the front to the rear; LTP cartilage thickness was thickest in the middle, second in the rear and thinnest in the front;MTP cartilage thickness was the thinnest in the front, was relatively uniform in the middle and rear and thicker than that in the front. CONCLUSION In Northeast China, among healthy adults aged 22 to 33, gender difference may be an important factor in the difference of cartilage thickness in various regions of the knee joint. Regardless of whether male or female healthy young people, the cartilage thickness of the entire knee joint is unevenly distributed, but there is no significant difference in cartilage thickness in the same area between the left and right knee joints.
Adult ; Adolescent ; Humans ; Male ; Female ; Young Adult ; Cartilage, Articular/diagnostic imaging* ; Knee Joint/surgery* ; Osteoarthritis ; Magnetic Resonance Imaging ; Femur

ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia， and provide prognosis indicators for the treatment of aplastic anemia （AA） with kidney-tonifying therapy in traditional Chinese medicine （TCM） combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment， the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age， sex， disease severity （including severe aplastic anemia and non-severe aplastic anemia）， course of disease， degree of bone marrow nucleated cell proliferation， baseline hemogram levels ［including white blood cell count （WBC）， absolute neutrophil count （ANC）， hemoglobin （HGB）， platelets （PLT）， and reticulocytes （RET）］， T lymphocytes subsets， and the expression levels of T-box transcription factor （T-bet） and GATA-binding protein-3 （GATA-3） were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of ［20， 40） and ［60， 80） were higher in the 4-month effective group （P<0.05）. The sex， disease severity， course of disease， and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB， WBC， ANC， and PLT than the 4-month ineffective group （P<0.05）， and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time， while other indicators did not affect the onset time. The receiver operating characteristic （ROC） curve was established to analyze the value of PLT level before treatment for predicting the onset time， and the area under the curve was 0.691. With the critical value of 40.5×10⁹/L， the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893， respectively. The two groups of patients were graded according to age ｛（14， 20）， ［20， 40）， ［40， 60）， and ［60， 80）｝ and PLT level before treatment （PLT<40×10⁹/L， PLT≥40×10⁹/L）. The proportion of the patients with PLT≥40×10⁹/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group （P<0.05）. The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment （P<0.05）. The levels of Th1 cells， Th2 cells， CD4⁺ T cells， and CD8⁺ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment （P<0.05）， while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of ［20， 40） or ［40， 60）， with higher levels of HGB， WBC， ANC， and PLT （especially those with PLT≥40×10⁹/L）， lower level of total T lymphocytes， or higher T-bet expression level before treatment.