Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

ObjectiveTo observe the effect of the Fangfeng Tongshengsan on post-chemoembolization syndrome with primary liver cancer or postoperative liver metastases of colorectal cancer. MethodSeventy-two patients suffered from post-chemoembolization syndrome after transcatheter hepatic arterial chemoembolization were randomly divided into 2 groups， including a Fangfeng Tongshengsan group and a control group， with 36 patients in each group. The patients in Fangfeng Tongshengsan group orally took the decoction for consecutive 7 d. The patients in the control group were physically cooled down with alcohol rub bath and ice pack for consecutive 7 d. Furthermore， the difference of fever， Karnofsky performance status （KPS）， pain in the liver region， nausea vomiting， constipation， and liver function between these two groups were observed. ResultCompared with the control group， Fangfeng Tongshengsan significantly relieved fever， reduced the body temperature （P<0.05）， and shortened the duration of fever （P<0.05）， indicating that Fangfeng Tongshengsan remarkably improved the KPS （P<0.05）. Meanwhile， Fangfeng Tongshengsan obviously alleviated nausea， vomiting， and constipation status and shortened the duration time compared with the control group （P<0.05）. In addition， the parameters of liver function including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptidase （GGT）， and total bilirubin （TBIL） were significantly decreased in the Fangfeng Tongshengsan group （P<0.05）， which indicated that Fangfeng Tongshengsan alleviated liver dysfunction of patients with post-chemoembolization syndrome. ConclusionFangfeng Tongshengsan can be used to treat post-chemoembolization syndrome with primary liver cancer and postoperative liver metastases of colorectal cancer.

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

We developed a high-efficiency microfluidic chip for extracting exosomes from human plasma. We collected peripheral blood from normal human, designed and fabricated a microfluidic chip based on nanoporous membrane and agarose gel electrophoresis to isolate exosomes. The extracted exosomes were characterized by transmission electron microscopy, nanosight and Western blotting, the morphology, concentration and particle size of exosomes were identified and analyzed. Meanwhile, we used ultracentrifugation and microfluidic chip to isolate exosomes separately. The particle size and concentration of the exosomes extracted by two methods were compared and analyzed, and their respective extraction efficiency was discussed. Finally, the expression level of miRNA-21 in exosomes was analyzed by RT-PCR. The microfluidic chip isolated (in 1 hour) high-purity exosomes with size ranging from 30-200 nm directly from human plasma, allowing downstream exosomal miRNA analysis. By comparing with ultracentrifugation, the isolation yield of microfluidic chip was 3.80 times higher than ultracentrifugation when the volume of plasma sample less than 100 μL. The optimized parameters for exosome isolation by gel electrophoresis microfluidic chip were: voltage: 100 V; concentration of agarose gel: 1.0%; flow rate of injection pump: 0.1 mL/h. The gel electrophoresis microfluidic chips could rapidly and efficiently isolate the exosomes, showing great potential in the research of exosomes and cancer biomarkers.
Exosomes ; Humans ; MicroRNAs/genetics* ; Microfluidics ; Plasma ; Ultracentrifugation

Objective To investigate the relationship between serum thyroid hormone level and prognosis after cerebral infarction.Methods Serum thyroid hormone level was determined in 88 patients with partial anteri-or circulation infarction(PACI)and large artery atherosclerotic(LAA)cerebral infarction.After 6-months rehabili-tation,the difference of serum thyroid hormone level was compared among all groups. Results Significant differ-ences of serum free triiodothyronine(FT3)were observed in patients with different prognosis(P < 0.01). Signifi-cant correlation was found between the low level FT3and the good prognosis(P < 0.01). Conclusions The de-crease of serum thyroid hormone level after cerebral infarction is protective,and the FT3level is negatively correlat-ed with the prognosis of patients with cerebral infarction.

Objective To investigate the distribution characteristics and changing tendency of urinary tract stones.Methods From January 2011 to May 2017,clinical data of 15 269 patients treated in our center was retrospectively reviewed.The stone components were detected by the automatic stone infrared spectroscopy system and the predominant components were recorded.There were 9 019 male patients and 6 250 female patients.The patients were divided into four groups according to their age,including group A ≤ 18 years;group B 19-40 years;group C 41-60 years;and group D ＞ 60 years.Compared the distribution characteristics of urinary tract stones of patient in different groups of sex,age and calendar year.Results Calcium oxalate stones were more prevalent in males than females [6 221 (69.0％)vs.3 582 (57.3％),P ＜ 0.001],but calcium phosphate stones [210 (3.4％) vs.210 (2.3％)],magnesium ammonium phosphate stones [230(3.7％) vs.165 (1.8％)] and carbonate apatite stones [1 328 (21.3％) vs.1 030 (11.4％)] were more common in females than males (P ＜ 0.001,respectively).The proportion of uric acid stones in group D [679(20.7％)] was higher than that in group A [23(9.1％)],group B[260(7.9％)],group C [1 163 (13.8％)] (P ＜0.001,respectively).The peak of carbonate apatite stones was showed in group B [652(19.7％)] (P＜0.001,respectively).Ammonium urate stones [9(3.5％)] and cystine stones [36 (14.2％)] were more frequent in group A(P ＜0.001,respectively).In adults,the percentage of uric acid stones increased with age,such as group B [260(7.9％)],group C [1 163(13.8％)],group D [679 (20.7％)].And the carbonated apatite stones decreased with age,such as group B [652 (19.7％)],group C [1 270(15.1％)],group D [416(12.7％)] (P ＜0.001,respectively).Further analysis showed the proportion of calc ium oxalate (OR =0.944,95 ％ CI 0.927-0.962,P ＜ 0.001),ammonium urate stones (OR =0.854,95％ CI 0.742-0.982,P =0.027) decreased,while calcium phosphate (OR =1.192,95％ CI 1.127-1.261,P ＜0.001),uric acid (OR =1.042,95％ CI 1.015-1.069,P =0.002) and ammonium magnesium phosphate (OR =1.078,95％ CI 1.019-1.141,P =0.009) stones increased with time.Conclusions The distribution of stones was different in genders and age.Calcium oxalate stones were more common in male patients,while ammonium magnesium phosphate and carbonate apatite stones were more common in female patients.Uric acid stones were more frequent in patients older than 60,while carbonate apatite were more frequent in the 19-40 age group.The proportion of calcium oxalate and ammonium urate stones showed a downward trend,whereas calcium phosphate,uric acid and magnesium ammonium phosphate stones increased with time.

Objective To assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL ) before 20 weeks′gestation and hypertensive disorder complicating pregnancy (HDCP);and to evaluate the predictive value of plasma TRAIL for HDCP.Methods A 2-phase screening/validation study was designed.In the screening phase , a nested, case-controlled study was performed , the plasma samples collected before 20 weeks′gestation from 20 women who later developed HDCP and 20 age-and gestation week-matched controls were tested in prospective screening test for protein expression profiling during pregnancy and HDCP.Plasma samples were analyzed by a human protein microarray technology designed to detect 507 proteins simultaneously.Differently expressed proteins′functional annotation and clustering were performed by using of Database for Annotation , Visualization and Integrated Discovery ( DAVID) and Gene Ontology ( GO) database.The TRAIL level of plasma samples obtained before 20 weeks′gestation from 53 women who later developed HDCP and 106 similarly matched controls were further validated by ELISA and 62 clinical risk factors were investigated.Logistic regression and ROC analysis were used to evaluate the relationship between TRAIL and HDCP and its predictive value for HDCP.Results In protein microarray analysis , 23 proteins expressed differently before 20 weeks′gestation between the two groups.Further validation results showed that TRAIL levels in HDCP patients were lower significantly (45.7 ±13.1) pg/ml than those in healthy pregnant controls (51.2 ±14.7)pg/ml, P=0.021.Multiple factor logistic regression analysis of 159 pregnancies showed that three features were finally entering the logistic model, they were:anemia (OR=4.87, 95% CI 1.05-24.26), pre-pregnancy BMI (OR=1.72, 95% CI 1.35 -2.19) and TRAIL (OR=0.96, 95% CI 0.92 -0.99).The predictive accuracy of logistic model was 81.8%.The model significantly increases the predictive value (AUC=0.81, 95%CI 0.73-0.87) compared to TRAIL as independent predictor (AUC=0.59, 95%CI 0.51-0.67).Conclusions Totally 23 proteins were expressed differentially before 20 weeks′gestation in plasma of women who later developed HDCP , confirming that HDCP is a heterogeneous disease with different biological changes.The data suggests that plasma TRAIL levels relate with the development of HDCP and its combination with pre-pregnancy BMI and anemia have a high predictive value for HDCP before 20 weeks′gestation.

Arsenic trioxide (ATO) has been identified as an effective treatment for acute promyelocytic leukemia (APL) but is much less effective against solid tumors such as hepatocellular carcinoma (HCC). In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yl)tryptophan methyl ester (ETME). Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP) in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.