The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective:To explore the genetic basis of a child with mental retardation and developmental delay.Methods:A child who had attended the genetic clinic of Linyi People′s Hospital from October 2023 to April 2024 was selected as the study subject. Intelligence and development were assessed with simplified Peabody scale. Electroencephalogram and imaging data were collected. Peripheral blood samples of the child and her parents were collected for the screening of genetic metabolic diseases, chromosomal karyotyping, and trio-whole genome sequencing (trio-WGS) analysis. Candidate variant was verified by Sanger sequencing, and RNAseq was carried out to verify the alternative splicing due to the candidate variant. This study has been approved by the Medical Ethics Committee of Linyi People′s Hospital (No. YX200083).Results:The patient was an 8-year-and-11-month-old girl. Both of her parents had normal phenotypes. The child was assessed by the simplified Peabody scale as having intellectual disability and developmental delay. MRI showed no definite abnormal signals within the brain parenchyma, and electroencephalogram was normal. Screening of genetic metabolic diseases showed no obvious abnormality. Chromosomal karyotype was normal. Trio-WGS has detected a c. 697+ 1G>A variant in the intron 4 of the NFIX gene, along with 9 other variants within eight genes. The c. 697+ 1G>A variant may cause abnormal splicing of the NFIX gene transcript. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 697+ 1G>A variant was predicted to be pathogenic (PVS1+ PS2+ PM2_Supporting), while the evidence for pathogenicity of the other 9 variants was insufficient. Conclusion:The novel de novo c. 697+ 1G>A variant of the NFIX gene probably underlay the pathogenesis of the child, which may have caused the disease by leading to abnormal splicing.

OBJECTIVE:To establish the method for the simultaneous determination of contents of 4 heavy metal elements in cultured Cordyceps militaris. METHODS:The samples were digested by nitric acid heating method and then determined by ICP-MS including radio-frequency power of 1.15 kW,sampling depth of 65 nm,auxiliary gas flow rate of 1.0 L/min,cooling gas flow of 13.0 L/min,temperature of 25 ℃,automatic plasma. RESULTS:The linear ranges of arsenic(As),cadmium(Cd),mer-cury (Hg) and lead (Pb) were 0-20 μg/mL(r=0.9970),0-10 μg/mL(r=0.9995),0-5 μg/mL(r=0.9955),0-20 μg/mL(r=0.9960),respectively. Detectio limit were 0.128,0.003,0.002,0.004 mg. RSDs of precision,stability and reproducibility tests were all lower than 6.5%. Recoveries of them were 90.4%-100.6%(RSD=3.45%,n=9),94.3%-101.3%(RSD=2.93%,n=9), 90.0%-102.3%(RSD=4.03%,n=9),92.3%-103.0%(RSD=3.53%,n=9),respectively. CONCLUSIONS:The method is sim-ple,precise,stable,reproducible,and can be used for simultaneous determination of contents of 4 heavy metal elements in cul-tured C. militaris. The contents of As,Cd,Hg and Pb in 10 batches of sample are all in line with related national standards.

OBJECTIVE:To establish a method for simultaneous determination of 5 nucleoside from different parts of cultured Cordyceps militaris. METHODS:HPLC method was adopted. The determination was performed on InertSustain C18 column with mobile phase consisting of methanol-0.02 mol/L monobasic potassium phosphate solution (gradient elution) at the flow rate of 0.6 mL/min. The detection wavelength was set at 254 nm,the column temperature was 30 ℃. RESULTS:The linear ranges of uridine, inosine,guanosine,adenosine and cordycepin were 0.568-3.408 μg(r=0.9999),0.284-1.704 μg(r=0.9999),0.264-1.584 μg(r=0.9999),0.232-1.392 μg(r=0.9999)and 1.672-10.032 μg(r=0.9998),respectively. RSDs of precision,stability and repeatabili-ty tests were all lower than 3.0%. The recoveries were 98.2%-103.9%(RSD=1.97%,n=9),96.2%-101.6%(RSD=1.76%,n=9),96.7%-102.0%(RSD=1.94%,n=9),95.1%-99.4%(RSD=1.43%,n=9) and 95.6%-101.3%(RSD=1.82%,n=9). CON-CLUSIONS:The method is simple,precise,stable and repeatable,and can be used for simultaneous determination of 5 nucleoside from cultured C. militaris,the content of nucleosides are different in different parts of C. militaris.

Objective To explore the rehabilitation needs and its influential factors of adults with physical disability in Shanghai, and to provide evidence for decision-making of the precise rehabilitation service. Methods From November to December, 2016, the rehabilitation demands, utilization rate and its influential factors of 390 registered people with physical disability were investigated with a questionnaire. Results The service of occupational rehabilitation met 62.34%and educational rehabilitation met 52.00%of the needs of adults with physi-cal disability at the age of 18 to 40 years. The service of occupational rehabilitation met 38.71%and educational rehabilitation met 35.29%of the needs of adults with physical disability of grade two. The main obstacle to the service utilization wasDo not know(67.34%). As a part ofotherreason, the cumulative frequency oftemporarily not neededaccounted for 16.41%in all reasons. Conclusion The rehabili-tation service should focus unmet needs to complete the community rehabilitation and health governance, and optimize the service system.

Thirteen compoumds were isolated from the n-BuOH portion of the 70% ethanolic extract of Comastoma pedunculatum by a combination of various chromatographic techniques including silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC, of which nine were triterpenoid saponins and four were flavone C-glycosides. Their structures were elucidated by spectroscopic data as saikogenin F (1), 3-O-beta-D-fucopyranosylsaikogenin F (2), clinoposaponin XV (3), saikosaponin A (4), 6"-acetylsaikosaponin A (5), clinoposaponin I (6), bupleuroside I (7) , clinoposaponin XII (8) , saikoponin b3 (9), isovitexin (10) , swertisin (11) , isoorientin (12), 3',4',5-trihydroxy-7-methoxy-6-C-beta-D-glucopyranosyl-flavone (13). Compounds 1-10, 12-13 were all isolated from Comastoma genus for the first time.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Flavones ; analysis ; isolation & purification ; Gentianaceae ; chemistry ; Saponins ; analysis ; isolation & purification ; Spectrometry, Mass, Electrospray Ionization

BACKGROUND: Disturbed regulation of cell cycle is the essential mechanism on abnormal proliferation of cell and incidence of cancer. CyclinD1 /cyclin-dependent-kinase pathway involved with p16 and retinoblastoma gene protein is an important.approach on regulation of cell cycle.OBJECTIVE: To understand the expressions of cyclinD1, p16 and retinohlastoma gene protein in non-small-cell lung cancer and probe into the relationship with the prognosis of cancer.DESIGN: Immunohistochemical assay was used to measure the expressions of relevant indexes and follow-up data were utilized for comparative analysis on survival rate and prognostic factor.SETTING: Department of Respiratory Disease, Fujian Provincial Hospital PARTICIPANTS: The experiment was performed in Department of Pathology of Fujian Provincial Hospital from January to June 2002. Tissue specimens of lung cancer were from 68 cases of non-small-cell lung cancer.Histological classification of lung cancer was based on the standards implemented by WHO in 1981 and TNM staging was on the standards revised by International Union Against Cancer (UICC) in 1997.METHODS: Tissue specimens of lung cancer were stained with immunohistochemical method, the positive-stained splices of lung cancer were taken as positive control and those with 1st antibody replaced by phosphate buffer were taken as negative control. The positive was identified if tumor cell nucleus or cytoplasm presented brown-yellow granules. 5 high-power visual fields were observed at randomize in each specimen and 200 tumor cells were counted and the average was obtained. According to the perceptions of positive cell, in which, positive cell count was less by 5% or no obvious positive cell appeared "-", positive cell count was in range from 5% to 20% "+", positive cell count was in range from 21% to 50% "++"and positive cell count was over 50% "(#)", the expression of cyclinD1,p16 and retinoblastoma gene protein in 68 cases of non-small-cell lung cancer were assayed.MAIN OUTCOME MEASURES: Expressions of cyclinD1, p16 and retinoblastoma gene protein and survival phase of patients after operation.retinoblastoma gene protein: The expressive rates were 55.9%, 48.5% and 52.9% respectively. X2 was applied for analysis on the data and it was indicated that there was no remarkable correlation among their expressions.gene protein and prognosis of non-small-cell lung cancer: The average survival phase of cyclinD1 positive expression was shorter than that of negative expression [(12.40, 35.40) months, (x2=5.31 ,P =0.021)]. The average survival phase of positive case of p16 positive expression was longer than that of negative one [(27.84, 15.95) months, (X2=4.38 ,P =0.036)].The average survival phase of positive expression of retinoblastoma gene protein was not more different significantly from the negative one [(18.50,of non-small-cell lung cancer with Cox proportional hazard model: It was indicated that the prognosis of excessive expression of cyclinD1 was poor (P=0.057) and that of p16 only presented 1 prognostic protective factor (P=0.039).CONCLUSION: CyclinD1, p16 and retinoblastoma gene associated with cyclinG1-S regulation are all involved in incidence and development of non-small-cell lung cancer. The assay of expressions of cyclinD1 and p16is essentially significant for prognosis.

Objective:　To investigate the effects of nimodipine on changes of endothelin after head injury. 　　Methods:　Sixty-five adult rabbits were randomized into an injury group (IG, n=30), a nimodipine-treatment group (NTG, n=30) and a control group (CG, n=5). With their heads unfixed, the animals in IG and NTG were injured in the frontal-parietal zone with BIM-II bioimpact. Blood samples and brain tissue were collected before and after injury. The endothelin level was measured with RIA. 　　Results:　The endothelin level in plasma and brain tissue was significantly increased 24 hours after injury. At the 8th or/and 24th hours postinjury, the endothelin level was significantly lower in NTG than that in IG. 　　Conclusions:　Nimodipine can prevent endothelin from elevation and act as a practical endothelin antagonist after head injury clinically.

OBJECTIVE: The dynamic response of the heart during chest impact and the characteristics of heart injuries were investigated to further understand the mechanisms of heart impact injuries. METHODS: Eleven dogs and thirty-four rabbits were subjected to front thoracic impact with different impact velocities and compression response. The accelerated movement of thoracic wall during the impact period was monitored. The pathological examination of the injured heart was done and the dynamic responses and mechanisms of injuries were analyzed with mathematics models. RESULTS: The analysis of mathematics model and experimental results showed that the injury severity of heart was well correlated with the viscous criterion. The thoracic wall was involved in bi-directional movement of compression and expansion. The injured heart showed spotty or stripy hemorrhages in the ventricle endocardium. Light microscopic examination showed interstitial bleeding and rupture of the myocardial fibers in the contusion area. The biomechanical analysis indicated that there was a large deformation caused by the stress concentration on the lateral ventricle wall. CONCLUSIONS: There is a high speed and excessive deformation of the heart during the impact period, which might be the key mechanism of heart injury. The strong impact and press coming from both sternum and vertebral column and the rapid elevation of pressure in the ventricle are the main cause of deformation.

0.05). Tumors metastasized in 10 of 25 primary NSCLC overexpressing cyclin D 1, but only in one of 21 cases that cyclin D 1 negatively expressed ( P