Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma.Methods:A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed.Results:Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with "kidney-shaped" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative.Conclusions:The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma.Methods:A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed.Results:Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with "kidney-shaped" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative.Conclusions:The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective To investigate the expression characteristics of BRAF,RAS and TERT genes in ultrasound-guided fine needle aspiration specimens and their application value in the preoperative diagnosis of thyroid nodules.Methods A retrospective analysis was performed on 537 cases of fine needle aspiration speci-mens of thyroid nodules in the Aviation General Hospital.The cell smear and liquid-based cell section prepara-tion from each specimen conducted the Papanicolaou's stain and the results were interpreted according to the Bethesda grading system.The gene mutation situation in punctured tissues was analyzed by real-time quantita-tive PCR.Results There were 65 cases (12.10％) of Bethesda class Ⅰ nodules,153 cases (28.49％) of class Ⅱ,84 cases (15.64％) of class Ⅲ,9 cases (1.68％) of class Ⅳ,73 cases (13.59％) of class Ⅴ and 153 cases (28.49％) of class Ⅵ.There were 220 cases (40.97％) of BRAF V600E mutation,21 cases (3.91％) of NRAS mutation,6 cases (1.12％) of KRAS mutation and 2 cases (0.37％) of HRAS mutation.Among them,there was BRAF V600E and KRAS co-mutation in 1 case.BRAF V600E gene mutation had the correlation with cytological diagnostic results (P<0.05),BRAF V600E mutation was more likely to occur in younger ones (P<0.05),and BRAF V600E mutation was more common in males than in females (P<0.05).KRAS mutation was more likely to occur in nodules in the left lobe of the thyroid gland (P<0.05).Conclusion BRAF V600E gene mutation is the most common among thyroid fine needle puncture specimens,and the NRAS mu-tation is in the majority for RAS gene mutations.

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase in vivo. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by in vitro enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model in vivo was established. Result:The IC₅₀ values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate in vivo of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% in vivo lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% in vivo lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and in vivo pharmacokinetic curves can effectively evaluate the in vivo inhibitory activity of compounds against the target.

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.
Chromatography, Liquid ; Chrysanthemum ; Flavonoids ; Kinetics ; Pharmaceutical Preparations ; Tandem Mass Spectrometry ; Xanthine Oxidase/metabolism*

OBJECTIVE： To screen the quality control components of Chrysanthemum morifolium based multiple component metabolism， and study its network pharmacology effect. METHODS： The water extract of C. morifolium was prepared. A total of one rats were selected， water extract of C. morifolium was perfused in jejunum segment after abdominal anesthesia； plasma sample 1 was collected by double perfusion collection. Other 3 rats were given water extract of C. morifolium intragastrically， and plasma sample 2 was collected by abdominal aorta blood collection. UPLC-MS/MS was used to analyze water extract of C. morifolium and plasma sample component， and prototype blood-entry component in water extract of C. morifolium was identified after metabolism. TCMSP and Swiss Target Prediction database were used to screen the core target of prototype blood-entry component. DAVID database was used to enrich the related pathways of core target. The quality control components were screened according to topological parameters. Cytoscape software was used to analyze pharmacological effect of quality control components of C. morifolium. RESULTS： After UPLC-MS/MS analysis， 27 compounds were identified in water extract of C. morifolium， among which there were 12 prototype blood-entry components. After network pharmacology analysis， 7 quality control components were identified， i.e. cosmosiin， apigenin-7-O-glucuronide， luteolin， tilianin， apigenin， hesperetin， acacetin. It was possible to treat cancer， cardiovascular and cerebrovascular diseases， and neurological diseases by acting on metabolic pathway， cancer related pathway， signal transduction related pathway， adipocyte lipolysis regulatory pathway， etc. CONCLUSIONS： The study screen the possible quality control components of water extract of C. morifolium. The theoretical pharmacological effect of it can be clarified through network pharmacology， which can provide a new idea for the utilization of C. morifolium.

Patient 1,a 25-year-old female with ectopic pregnancy received an IV infusion of desmopressin acetate 15 μg every 12 hours due to tubal embryo surgery incision and pelvic adhesion separation surgery. On day 2,about 30 minutes after the start of infusion,the patient developed delirium, confusion,convulsion, and trismus. Laboratory tests showed that serum sodium was 125 mmol/ L (preoperative serum sodium was 142 mmol/ L). Hyponatremic encephalopathy induced by desmopressin acetate was considered. Desmopressin acetate was withdrawn immediately and she was given sodium supplement. About 10 minutes later,the patient's symptoms relieved. She had consciousness and serum sodium level rose to 141 mmol/ L on the next day. Patient 2,a 42-year-old female patient received an IV infusion of desmopressin acetate 18 μg every 12 hours after radical treatment of perianal abscess. On day 4, the patient developed dizziness,sweating,tremor of hands,chills,and oliguria. On day 5,the patient developed nausea,upward deviation of the eyes,and muscular rigidity and clonus in both upper limbs. Laboratory tests showed that serum sodium was 124 mmol/ L(preoperative serum sodium was 141 mmol/ L). Her CT examination showed extensive edema in white matter of the cerebral hemisphere. Hyponatremic encephalopathy induced by desmopressin acetate was considered. Desmopressin acetate was stopped and she was given symptomatic treatments such as sodium supplement. One day later,the patient' s symptoms disappeared and her serum sodium increased to 138 mmol/ L.

Patient 1,a 25-year-old female with ectopic pregnancy received an IV infusion of desmopressin acetate 15 μg every 12 hours due to tubal embryo surgery incision and pelvic adhesion separation surgery. On day 2,about 30 minutes after the start of infusion,the patient developed delirium, confusion,convulsion, and trismus. Laboratory tests showed that serum sodium was 125 mmol/ L (preoperative serum sodium was 142 mmol/ L). Hyponatremic encephalopathy induced by desmopressin acetate was considered. Desmopressin acetate was withdrawn immediately and she was given sodium supplement. About 10 minutes later,the patient's symptoms relieved. She had consciousness and serum sodium level rose to 141 mmol/ L on the next day. Patient 2,a 42-year-old female patient received an IV infusion of desmopressin acetate 18 μg every 12 hours after radical treatment of perianal abscess. On day 4, the patient developed dizziness,sweating,tremor of hands,chills,and oliguria. On day 5,the patient developed nausea,upward deviation of the eyes,and muscular rigidity and clonus in both upper limbs. Laboratory tests showed that serum sodium was 124 mmol/ L(preoperative serum sodium was 141 mmol/ L). Her CT examination showed extensive edema in white matter of the cerebral hemisphere. Hyponatremic encephalopathy induced by desmopressin acetate was considered. Desmopressin acetate was stopped and she was given symptomatic treatments such as sodium supplement. One day later,the patient' s symptoms disappeared and her serum sodium increased to 138 mmol/ L.