OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.

Objective To investigate the expression of circRAF1 in primary ovarian insufficiency(POI)and explore its effect on cell proliferation and apoptosis of human ovarian granulosa cells(GCs)line(KGN cells).Methods The expression of circRAF1 in GCs and serum of patients with normal ovarian reserve function(n = 50)and patients with POI(n = 50)were detected with RT-qPCR.The correlation of circRAF1 with ovarian reserve function indexes was analyzed.Small interfering RNA(siRNA)targeting circRAF1 was constructed and trans-fected into KGN cells,with the cell proliferation detected by CCK-8 and EdU assay,and the cell apoptosis detected by JC-1 and Tunel assay.The mRNA and protein levels of genes related to cell proliferation and apoptosis(FSHR,PCNA,Bcl-2,Casp-9,Bax)were detected by RT-qPCR and WB.Results The expression of circRAF1 decreased in GCs and serum of POI patients.The expression of circRAF1 was positively correlated with serum E2 and AMH levels(P<0.001),but negatively correlated with serum FSH and LH levels(P<0.001).At the same time,the expression of circRAF1 was positively correlated with AFC(P<0.001).Interfering with the expression of circRAF1 could inhibit the proliferation of KGN cells and promote their apoptosis.Conclusion The expression of circRAF1 in the GCs and serum of POI patients is down-regulated,which is correlated with the decline of ovarian reserve function.Interfering with circRAF1 can inhibit the proliferation of GCs and promote their apoptosis.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8％),516 patients with major depressive disorder(57.1％),and 102 patients with bipolar disorder(26.8％)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

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