Objective To explore characteristics of patients with drug-induced liver injury(DILI),suspected drugs and outcomes,and to provide reference for clinical standard use of drugs and reduce adverse reactions of DILI.Methods Retrospective analysis of adverse drug reactions of 281 patients with DILI in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from 2016 to 2023.Age,sex,severity,clinical manifestations,clinical classification,Roussel Uclaf causality assessment method(RUCAM)score,injury degree,combination,disease type,suspected drugs and outcomes of patiengs were statistically analyzed.Results Among 281 patients with DILI,there were 83 general ADRs cases and 198 serious ADRs cases.In terms of clinical manifestations,main manifestations were yellow skin sclera,poor appetite,fatigue and so on.In terms of injury degree,156 cases suffered mild liver injury,121 cases suffered moderate liver injury,and 4 cases suffered severe liver injury.There were 164 cases of combined drug use and 117 cases of single drug use.The top diseases of patients were tumor,respiratory disease,tuberculosis infection and so on.Among the suspected drugs,the top three drugs were Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs in order,and there were significant differences between different types of suspected drugs and whether they were used in combination(P＜0.05).There were significant differences in clinical classification and effectiveness(P＜0.05).Conclusion Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs are relatively easy to cause DILI.The type of liver cell damage,combination of drugs,types of diseases,and underlying diseases all affect the occurrence of DILI.

Objective To explore characteristics of patients with drug-induced liver injury(DILI),suspected drugs and outcomes,and to provide reference for clinical standard use of drugs and reduce adverse reactions of DILI.Methods Retrospective analysis of adverse drug reactions of 281 patients with DILI in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from 2016 to 2023.Age,sex,severity,clinical manifestations,clinical classification,Roussel Uclaf causality assessment method(RUCAM)score,injury degree,combination,disease type,suspected drugs and outcomes of patiengs were statistically analyzed.Results Among 281 patients with DILI,there were 83 general ADRs cases and 198 serious ADRs cases.In terms of clinical manifestations,main manifestations were yellow skin sclera,poor appetite,fatigue and so on.In terms of injury degree,156 cases suffered mild liver injury,121 cases suffered moderate liver injury,and 4 cases suffered severe liver injury.There were 164 cases of combined drug use and 117 cases of single drug use.The top diseases of patients were tumor,respiratory disease,tuberculosis infection and so on.Among the suspected drugs,the top three drugs were Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs in order,and there were significant differences between different types of suspected drugs and whether they were used in combination(P＜0.05).There were significant differences in clinical classification and effectiveness(P＜0.05).Conclusion Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs are relatively easy to cause DILI.The type of liver cell damage,combination of drugs,types of diseases,and underlying diseases all affect the occurrence of DILI.

Aim To explore the mechanism of oxiracetam promoting neurogenesis and migration in rats with cer-ebral infarction through stromal cell-derived factor-1α(SDF-1α)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods 100 SD rats were randomly divided into control group,cerebral ischemia(CI)group,oxiracetam(200 mg/kg)group,and oxiracetam(200 mg/kg)+AMD3100(5 mg/kg)group,with 25 rats in each group.Electrocoagulation was used to create rat model of local permanent cerebral infarction.After 1,7 and 14 days of modeling,neurological deficits were scored,TTC staining was used to detect the volume of cerebral infarction,Nissl staining was used to detect cell surviv-al in the infarcted area,Western blot was used to detect SDF-1α and CXCR4 protein levels in ischemic zone.After 1～7 days of modeling,BrdU(50 mg/kg)was continuously injected intraperitoneally.After 14 days,immunofluorescence double staining was used to detect the number of BrdU+Nestin+and BrdU+DCX+cells in the SVZ region.5 days before modeling,retroviruses carrying GFP were injected into the SVZ region.After 14 days,immunofluorescence double stai-ning was used to detect the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in infarction area.C17.2 cells were divided into control group,oxygen-glucose deprivation(OGD)group,oxiracetam(final concentration:200 mg/L)group,and oxiracetam(final concentration:200 mg/L)+AMD3100(final concentration:100 μmol/L)group.OGD was used to create cell CI model.After 12 hours,immunofluorescence double staining was used to detect the number of Br-dU+/Nestin+and BrdU+/MAP-2+cells,Transwell experiment was used to detect cell migration,Western blot was used to detect SDF-1α and CXCR4 protein levels in cell culture supernatant.Results Animal experiment results showed:compared with control group,mNSS score in CI group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased(P＜0.05);compared with CI group,mNSS score in oxiracetam group was decreased,cerebral infarction volume was decreased,the number of surviving cells in infarc-ted area was increased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in in-farcted area were increased(P＜0.05);compared with oxiracetam group,mNSS score in oxiracetam+AMD3100 group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,CXCR4 protein level was decreased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in the SVZ region were de-creased(P＜0.05).Cell experiment results showed:compared with control group,the number of BrdU+/Nestin+and Br-dU+/MAP-2+cells in OGD group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with OGD group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with oxiracetam group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam+AMD3100 group were decreased,the number of cell migration,CXCR4 protein level in cell culture supernatant were decreased(P＜0.05).Conclusion Oxiracetam may promote the migration of neural stem cells from the SVZ region to the ischemic zone,promoting neurogenesis and functional recovery in rats with cerebral infarction by activating SDF-1α/CXCR4 pathway.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Purpose To investigate the expression and sig-nificance of CH25H and STAT3 in follicular lymphoma(FL).Methods Differentially expressed genes in FL and normal lymph node tissues from the GEO were screened.Paraffin sam-ples from 54 cases of FL and 20 cases of reactive proliferative lymph node tissue were collected.Immunohistochemical methods were used to detect the expression of CH25H and STAT3 in par-affin samples,and their relationship with the clinical and patho-logical characteristics of FL was analyzed.Results The expres-sion of CH25H mRNA in FL was significantly higher than that in normal lymph node tissue(P＜0.01).The expression level of CH25H mRNA in FL was linearly correlated with STAT3(P＜0.01).The high expression rate of CH25H in FL was 48.1％,which significantly higher than that in reactive proliferative lymph node tissue(15.0％,P＜0.05).The high expression rate of STAT3 was 59.3％,which significantly higher than that of reactive proliferative lymph node tissue(25.0％,P＜0.05).The expression level of CH25H protein was significantly correla-ted with the pathological grading and clinical Ann Arbor staging of FL(all P＜0.05).CH25H expression was higher in FL with high Ki67 expression(≥30％),while it was lower in FL with low Ki67 expression,and the difference was significant(P＜0.05).There was no significant correlation between CH25H and patient age,gender,presence or absence of B symptoms,ex-pression of CD10,BCL6,BCL2,FLIPI-1 score,lymphocyte count,and monocyte count(all P＞0.05).The expression lev-el of STAT3 protein was significantly correlated with the patho-logical grading,clinical Ann Arbor staging,and FLIPI-1 score of FL(all P＜0.05).STAT3 expression was higher in FL with high Ki67 expression(≥30％),while it was lower in FL with low Ki67 expression,and the difference was significant(P＜0.05).STAT3 was not significantly correlated with patient age,gender,presence or absence of B symptoms,expression of CD10,BCL6,BCL2,lymphocyte count,and monocyte count(all P＞0.05).The expression levels of CH25H and STAT3 in FL were positively correlated(r=0.573,P＜0.001).Conclu-sion The expression levels of CH25H and STAT3 proteins in FL are significantly increased,which can serve as potential mo-lecular markers for pathological diagnosis,grading,and progno-sis evaluation of FL.Abnormal expression of CH25H and STAT3 may jointly participate in the occurrence and progression of FL.

Purpose To investigate the expression and sig-nificance of CH25H and STAT3 in follicular lymphoma(FL).Methods Differentially expressed genes in FL and normal lymph node tissues from the GEO were screened.Paraffin sam-ples from 54 cases of FL and 20 cases of reactive proliferative lymph node tissue were collected.Immunohistochemical methods were used to detect the expression of CH25H and STAT3 in par-affin samples,and their relationship with the clinical and patho-logical characteristics of FL was analyzed.Results The expres-sion of CH25H mRNA in FL was significantly higher than that in normal lymph node tissue(P＜0.01).The expression level of CH25H mRNA in FL was linearly correlated with STAT3(P＜0.01).The high expression rate of CH25H in FL was 48.1％,which significantly higher than that in reactive proliferative lymph node tissue(15.0％,P＜0.05).The high expression rate of STAT3 was 59.3％,which significantly higher than that of reactive proliferative lymph node tissue(25.0％,P＜0.05).The expression level of CH25H protein was significantly correla-ted with the pathological grading and clinical Ann Arbor staging of FL(all P＜0.05).CH25H expression was higher in FL with high Ki67 expression(≥30％),while it was lower in FL with low Ki67 expression,and the difference was significant(P＜0.05).There was no significant correlation between CH25H and patient age,gender,presence or absence of B symptoms,ex-pression of CD10,BCL6,BCL2,FLIPI-1 score,lymphocyte count,and monocyte count(all P＞0.05).The expression lev-el of STAT3 protein was significantly correlated with the patho-logical grading,clinical Ann Arbor staging,and FLIPI-1 score of FL(all P＜0.05).STAT3 expression was higher in FL with high Ki67 expression(≥30％),while it was lower in FL with low Ki67 expression,and the difference was significant(P＜0.05).STAT3 was not significantly correlated with patient age,gender,presence or absence of B symptoms,expression of CD10,BCL6,BCL2,lymphocyte count,and monocyte count(all P＞0.05).The expression levels of CH25H and STAT3 in FL were positively correlated(r=0.573,P＜0.001).Conclu-sion The expression levels of CH25H and STAT3 proteins in FL are significantly increased,which can serve as potential mo-lecular markers for pathological diagnosis,grading,and progno-sis evaluation of FL.Abnormal expression of CH25H and STAT3 may jointly participate in the occurrence and progression of FL.

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

Objective:To construct a droplet digital PCR (ddPCR) for quantification of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine.Methods:The genome of SARS-CoV-2 BA.1 strain was used as the target gene. A set of primer and probe was designed based on the conserved sequence of spike protein, and the ddPCR for quantification of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine was established. The linearity, accuracy, specificity, repeatability and durability of the method were verified.Results:The optimal annealing temperature for ddPCR was 63℃. When the number of virus particles was in the range of 5×10 5-2×10 7 VP/ml, the linearity and the recovery rate of the method were good; the specificity of the probe and primer was good; the coefficient of variation (CV) values of the repeatability and the intermediate precision were within 10%; the CV value of the durability was within 15%. When comparing ddPCR with qPCR, the CV values were all within 10%. Conclusions:The established ddPCR had high sensitivity, good stability and strong specificity, suggesting that it could be used for the quantitative detection of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

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