BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Aromatic compounds make up a large part of fragrances and are traditionally produced by chemical synthesis and direct extraction from plants. Chemical synthesis depends on petroleum resources and has disadvantages such as causing environment pollutions and harsh reaction conditions. Due to the low content of aromatic compounds in plants and the low yield of direct extraction, plant extractions require large amounts of plant resources that occupy arable land. In recent years, with the development of metabolic engineering and synthetic biology, microbial synthesis of aromatic compounds from renewable resources has become a promising alternative approach to traditional methods. This review describes the research progress on the synthesis of aromatic fragrances by model microorganisms such as Escherichia coli or yeast, including the synthesis of vanillin through shikimic acid pathway and the synthesis of raspberry ketone through polyketide pathway. Moreover, this review highlights the elucidation of native biosynthesis pathways, the construction of synthetic pathways and metabolic regulation for the production of aromatic fragrances by microbial fermentation.
Biosynthetic Pathways ; Metabolic Engineering ; Odorants ; Shikimic Acid ; Synthetic Biology

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Objective To investigate the effects of concomitant administration oftryptophan on depression-related and anxiety-like behaviors of fluoxetine treated adult rats.Methods Sixty male Wistar rats were divided into the following groups by randomized block design:control group,L-tryptophan group,fluoxetine group,and experimental group (n=15);9 g/L sodium chloride injection (5 ml/kg),50 mg/kg L-tryptophan,10 mg/kg fluoxetine and both 50 mg/kg L-tryptophan and 10 mg/kg fluoxetine were,respectively,given to the rats in the above four groups via intragastric administration;depression models were established by 21 d-long-term chronic,medium and unpredictable stress stimulation.The modified forced swimming test (FST) was used to detect the times spent in immobility behavior,swimming behavior and climbing behavior;and elevated plus-maze (EPM) was employed to detect the times spent in open arms,closed arms and center area,and ratio of entries into open arms to the total entries;while tryptophan levels in cerebrospinal fluid were measured by high performance liquid chromatography.Results The times spent in immobility behavior,swimming behavior and climbing behavior showed significant differences among the four groups (P＜0.05);both fluoxetine and tryptophan had significant influences in FST results.The times spent in open arms,closed arms and center area showed significant differences among the four groups (P＜0.05);fluoxetine had significant influences in EPM results,and tryptophan had no significant influences in times spent in open arms,closed arms and center area;moreover,there was no significant interaction between tryptophan and fluoxetine treatments in parameters of FST and EPM.Significant difference of tryptophan level was noted among the four groups (F=6.874,P=0.002);that in the experimental group was significantly higher than that in the fluoxetine and control group (P＜0.05).Conclusions Tryptophan can increase depressive-related behavior,but not alter anxiety-like behavior.Fluoxetine can decrease depression-related behavior,but induce anxiety.Concomitant use oftryptophan and fluoxetine does not alter anxiety-like behavior and the antidepressant effect offluoxetine is not enhanced.

Objective To explore the effect of treating posterolateral tibial plateau fractures via the fibular osteotomy approach.Methods From August 2009 to August 2011,17 patients with posterolateral tibial plateau fractures,including 12 males and 5 females,aged from 24 to 76 years (average,37.8 years),were treated via the fibular osteotomy approach in our hospital.According to the Schatzker classification,8 cases were type Ⅱ,3 cases were type Ⅲ,6 cases were type V.After operation,X-rays were taken in all patients,and Rasmussen's radiological and functional gradings were used to evaluate radiological and functional outcomes of knees.Results All patients obtained follow-up,ranged from 9 to 35 months (average,18months).The healing time of the fracture ranged from 10.0 to 18.0 weeks (average,13.5 weeks).During the period of followed-up,there was no loss of reduction; one case presented with symptoms of common peroneal nerve injury,such as local hypesthesia in distal lateral lower leg and dorsi pedis,which recovered two weeks postoperatively.According to Rasmussen's radiological grading,the mean score of the knee joint was 17.5(range,14.0 to 18.0).The range of motion of the knee joint ranged from -5°to 135°(average,123.5o).According to Rasmussen's functional grading,the mean score of the knee joint was 26.9 (range,22 to 30).Conclusion Treating posterolateral tibial plateau fractures via the fibular osteotomy approach can obtain sufficient exposure,good reduction and fixation,and avoid flexion contracture of the knee and peripheral vascular nerve injury.Moreover,postoperative function and stability of the knee joint recover well.

Objective To analyze the complete genome sequence of Guangxi HEV isolate swGX32 and to compare it with other HEV isolates. Methods The overlapping fragments of HEV isolate swGX32 were amplified with reverse-transcription nested polymerase chain reaction (RT-nPCR),and the 5′ and 3′ ends of viral genome were amplified with rapid amplification of cDNA ends (RACE). The PCR products were cloned and sequenced. The sequence and phylogenetic analysis of swGX32 was performed. Results The genome of swGX32 consisted of 7240 nt excluding the polyA tail, with 4 nt overlapping between ORF1 and ORF2. ORF3 is contained in the sequence of ORF2. The complete genome sequence of swGX32 shared identity of 73%-74%, 73%, 74%-75%,83%-94% with HEV genotype 1,2,3 and 4, respectively. Among all these HEV reference sequences, swGX32 showed the highest identity with the human isolate JKO-ChiSai98C (94%). Phylogenetic tree showed that swGX32 belonged to genotype 4 and clustered with JKO-ChiSai98C in the branch of HEV subtype 4a. Conclusion The swine HEV isolate swGX32 is closely related to human strain JKO-ChiSai98C genetically and phylogenetically, which further provides molecular biology evidence of hepatitis E as a zoonosis.