Objective:To explore the clinical manifestations,pathological features,immunophenotype,as well as diagnosis,treatment and prognosis of patients with CD4-CD56+blastic plasmacytoid dendritic cell neoplasm(BPDCN),in order to further understand the rare disease.Methods:The clinical data,laboratory examinations and treatment regimens of two patients with CD4-CD56+BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed.Results:The two patients were both elderly males with tumor involved in skin,bone marrow,lymph nodes,etc.Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive,while CD4,CD34,TdT,CD3,CD20,MPO and EBER were negative.Flow cytometry of bone marrow demonstrated that CD56,CD123,and CD304 were all positive,while specific immune markers of myeloid and lymphoid were negative.Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens,but prone to rapid relapse.The overall survival of both patients was 36 months and 4 months,respectively.Conclusion:CD4-CD56+BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis.Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Objective The aim of this study was to compare the effect of injection of indocyanine green(ICG)through peripheral vein and gallbladder in laparoscopic cholecystectomy(LC)of difficult gallbladder.Methods Patients with difficult gallbladder who underwent LC by the same surgical team from May to October 2023 in the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Anhui University of Science and Technology were divided into three groups according to A random number table.Group A was injected ICG through peripheral vein before operation,group B was injected ICG through gallbladder during operation,and group C was the control group.The differences of operation time,intraoperative blood loss,hospitalization time,hospitalization cost and postoperative complications among the three groups were compared,and the effects of fluorescence mode cholangio-gram in group A and group B were compared.One-way analysis of variance was used to compare the normal distri-bution of the measurement data among groups,and LSD-t test was used to compare the two groups.The counting data was compared by chi-square test.The Boferroni test was appied to compare the two groups.Results There were no differences in length of stay,hospitalization cost and postoperative complications among the three groups(P＞0.05).The operative time and intraoperative blood loss of group A and group B were lower than those of group C(P＜0.05),but there was no difference between group A and group B(P＞0.05).The total imaging rate of the first three tubes of free gallbladder triangle(early stage)in group A was 41.67%,which was significantly lower than that in group B(63.89%)(P＜0.05).Conclusion ICG is beneficial for the identification of extrahepatic bile duct structures during LC of difficult gallbladder,and ICG injection through the gallbladder is helpful for the early identification of extrahepatic bile duct.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

The National Medical Products Administration have become an official applicant of the Pharmaceutical Inspection Co-operation Scheme(PIC/S)in 2023,and the good manufacturing practice appendix and inspection memorandum are key documents of PIC/S.Based on the analysis of the history,framework and main contents of the appendix and inspection memorandum of PIC/S investigational medicinal products,this paper discusses the key contents of the appendix and inspection memorandum of PIC/S clinical trial drugs,and provides reference for the inspection work.

Objective To evaluate the bioequivalence of the vardenafil hydrochloride tablets in fasting and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A randomized,open,single-dose,two-preparation,two-sequence,two-period,crossover design was used,and 40 healthy male subjects enrolled in the fasting state and 66 healthy male subjects enrolled in the fed state.The trial was conducted in two cycles,with 20 mg of either the subject formulation or the reference formulation,vardenafil hydrochloride tablets,being administered in each cycle.The drug concentration of vardenafil in plasma was determined by the liquid chromatography-tandem mass spectrometry(LC/MS-MS)method.Pharmacokinetic parameters were calculated using the non-compartment model,and the safety evaluation indexes were statistically analyzed using SAS 9.4 or above version program data statistical software.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fasting state:Cmaxwere(34.94±18.33)and(36.69±19.45)ng·mL-1;AUC0-t were(74.38±34.11)and(74.25±33.37)ng·mL-1·h;AUC0-∞ were(76.70±34.36)and(76.46±33.84)ng·mL-1·h,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fed state:Cmax were(22.84±12.48)and(21.68±11.12)ng·mL-1;AUC0_twere(70.82±35.88)and(72.71±34.63)ng·mL-1·h;AUC0-∞ were(73.48±36.44)and(75.29±35.12)ng·mL-1·h,respectively.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters such as Cmax,AUC0-t and AUC0-∞ of the prototype drug vardenafil in plasma after oral administration of 20 mg of the test and reference formulations of vardenafil tablets to the subjects in fasting and postprandial states fell within the equivalence interval of 80.00％to 125.00％.Conclusion The subject formulation of vardenafil hydrochloride tablets was bioequivalent to the reference formulation in fasting and fed conditions in healthy Chinese subjects.

Studies on chemical constituents in the rhizome of Dalbergia rimosa Roxb. The chemical constituents from the ethyl acetate part of D. rimosa were isolated and purified by silica gel, MCI gel, Sephadex LH-20 gel and semi-preparative HPLC, and the stuctures were identified by spectral method. Thirteen compounds were isolated from the ethyl acetate part of the rhizome of D. rimosa and identified as dalbergiaisoflavones A, B (1, 2), formononetin (3), 7,4′-dimethoxyisoflavone (4), 4′,6,7-trimethoxyisoflavone (5), biochanin A (6), prunetin (7), 7-O-methyltectorigenin (8), 3′-hydroxydaidzein (9), orobol 7,3′-dimethyl ether (10), 2′,7-dihydroxy-4′,5′- dimethoxyisoflavone (11), pruinosanone E (12), caviunin (13). Compounds 1 and 2 are new compounds, and compounds 3-13 were isolated from this plant for the first time. Compounds 9 and 11 had remarkable scavenging effect on DPPH free radicals.