Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

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.

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.
Humans ; COVID-19 ; SARS-CoV-2 ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Graft vs Host Disease

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Hemostatics ; Quality Control ; Rats ; Rhizome ; Saponins

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

【Objective】 To analyze the metagenomics and microbiology of voluntary blood donors in China, so as to assess the potential threats of emerging infectious diseases to the safety of blood transfusion. 【Methods】 12 300 plasma samples (10 mL each) collected by central blood stations in Chongqing, Liuzhou, Urumqi, Mianyang, Wuhan, Nanjing, Mudanjiang, and Dehong Prefecture area from 2012 to 2018 were subjected to total DNA extraction after ultracentrifugation (32 000 rpm/min, centrifugal radius 91.9 mm) in minipools of 160 donations. The metagenomic library was constructed, and deep sequencing was conducted by Illumina Hiseq 4 500. By comparing with reference sequences of bacteria, fungi, parasites and viruses, metagenomic data were analyzed, classification of microbes were identified, and potentially harmful pathogens were evaluated. 【Results】 A total of 632 GB clean data were obtained by deep sequencing, and the top three pathogens were Pseudomonas(0.561 1%), Burkholderia(0.468 7%) and Serratia(4.242 0%). Pathogens with potential threat which could be transmitted by blood transfusion or blood products were found, such as human parvovirus B19(0.126 6%), Leishmania spp(1.348 5%) and Toxoplasma gondii(0.615 8%). 【Conclusion】 Our study analyzed metagenomics of voluntary blood donors in parts of China and revealed pathogens that may cause potential harm to blood safety, which were helpful for targeted prevention and control of emerging infectious diseases.

ObjectiveThe purpose of this study was to compare the expression of plasma vWF activity， ADAMTS-13 activity and neutrophil-to-lymphocyte ratio （NLR） between patients with acute pulmonary thromboembolism （PTE） and healthy controls， and to explore the clinical value of plasma ADAMTS-13 activity and NLR in diagnosis of acute PTE. MethodsTotally 64 patients with acute PTE and 30 healthy controls were included. Collected clinical data and detected the plasma vWF activity and ADAMTS-13 activity by enzyme linked immunosorbent assay （Elisa）. The correlation between ADAMTS-13 activity and other clinical indexes was explored. Receiver operating characteristic curve （ROC） was mapped to evaluate the activity of ADAMTS-13 and NLR in the diagnosis of patients with acute PTE. ResultsThe comparison between the healthy control group and the acute pulmonary thromboembolism group showed that the ADAMTS-13 activity levels were 83.8% （72.2%， 98.8%） and 63.3% （49.6%， 74.8%）， respectively， the VWF activity levels were 102.7% （89.7%， 117.2%） and 122.6% （96.8%， 156.6%）， respectively， and the differences between the two groups were statistically significant （P＜0.05）. Spearman correlation analysis showed that there was a negative linear correlation between ADAMTS-13 activity and vWF activity with D-dimer （P＜0.05）. The results of multivariate Logistic regression showed that the increase of NLR was an independent risk factor for acute PTE ［OR=1.66， 95% CI （1.10， 2.47）， P=0.014］ and the increase of ADAMTS-13 activity was an independent protective factor for acute PTE ［OR=0.92， 95% CI （0.88， 0.964）， P＜0.001］. When used in the diagnosis of acute PTE， the area under the curve （AUC） for ADAMTS-13 activity was 0.861， 95%CI （0.780， 0.942）， P＜0.001. When combined with NLR， the AUC was 0.902， 95%CI（0.841， 0.963）， P＜0.001. ConclusionsOur results show plasma ADAMTS-13 activity is significantly decreased and vWF activity is significantly increased in patients with acute PTE. ADAMTS-13 and vWF may be the bridge between thrombosis and inflammation. Combined with NLR， plasma ADAMTS-13 activity can improve the accuracy of diagnosis of acute PTE. Our results provide new ideas for exploring the pathogenic mechanism of acute PTE， and provide experimental basis for exploring therapeutic target of acute PTE.

DNA Copy Number Variations/genetics* ; Genetic Testing ; Humans ; Motor Neurons ; Multiplex Polymerase Chain Reaction ; Muscular Atrophy, Spinal/genetics*