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.

Vaccination is an effective way to reduce the morbidity and mortality of infectious diseases. As a needle-free transcutaneous immunization (NF-TCI) vaccination technology, microneedles (MNs), composed of multiple micro-needles orderly attached to a substrate, can overcome the problems of low immune efficiency, poor compliance and waste of resources that exists in the conventional vaccination by injection, thus becoming a research hotspot in biomedicine. The microneedle vaccine can directly break through the stratum corneum barrier of the skin without touching nerves and blood vessels in the dermis, and effectively delivers the vaccine to the immune cells in the skin tissue to initiate the immune response of the body, thus triggering strong humoral and cellular immune processes. Vaccine delivery via the MNs system possesses the advantages of high safety, satisfying immune effect and practical economy, and shows great prospect in the prevention and treatment of infectious diseases and antineoplastic therapy. This article reviews the development background of MNs in transcutaneous immunization, the types of vaccine delivery, the factors affecting the immune effect, the problems to be solved and development direction in the future.

The enzymes CYP1 A2 and CYP3 A4 were measured by building a "Cocktail" probe drug and the incubation system of liver microsomes. The compatibility of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix on CYP450 enzyme protein and gene expression was explored from the level of protein and molecular biology. It explored the molecular mechanism of compatibility detoxication of Aconiti Lateralis Radix Praeparata to provide scientific support for clinical safe and effective application of Aconiti Lateralis Radix Praeparata. The CYP450 enzyme activity was determined by using "Cocktail" probe drugs. The content of CYP450 enzyme was measured by CO reduction of differential spectrum method. The mRNA expression of CYP1 A2 and CYP3 A4 enzyme was detected by RT-PCR technology. Compared with the blank group, the CYP1 A2 and CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group with significant differences(P<0.05), while the CYP3 A4 enzyme activity and mRNA expression were no influence in the Aconiti Lateralis Radix Praeparata group. The CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The content of CYP450 enzyme was decreased in the Aconiti Lateralis Radix Praeparata group, contributed to extremely significant difference(P<0.01). The content of CYP450 enzyme was increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The CYP1 A2 and CYP3 A4 enzyme activity and gene expression were enhanced after dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata. The metabolism of toxic ingredients of Aconiti Lateralis Radix Praeparata was accelerated to reach an effect of detoxication. The detoxication mechanism of compatibility of Aconiti Lateralis Radix Praeparata was verified from the viewpoint of liver metabolic enzymes.
Aconitum ; Drugs, Chinese Herbal ; Liver

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

【Objective】To determine the effect of ovarian stimulation or in vitro maturation for fertility preservation in female cancer patients. 【Methods】 A retrospective study was conducted in 27 females who underwent fertility preservation procedures in our center.【Results】Female patients were included in this study with an average age of 27.1. Patients spent on average for 6.8 d to retrieve oocytes since their attendance day. Total amount of Gn was on average 910 U per patient and for patients with breast cancer，the average estrogen level on trigger day reached 360 pg/mL. The maturation rate of oocytes from ovarian stimulation cycles was 82.6% ，which of that in emergency in- vitro maturation cycles was 38.1%.【Conclusion】The development capability of oocytes from cancer patients are comparable with those of other infertility patients. Peak estradiol levels were controlled by the administration of letrozole. In vitro maturation of oocytes performed at random time of the menstrual cycle may result in a lower maturation rate ，which is associated with the time limit of the follow- up cancer treatment. In conclusion，clinicians should consider a more holistic approach for female cancer patients，which focuses not only on the characteristic of the primary cancer but also on the phase of the menstrual cycle at their attendance day.

[Objective]To compare early serum beta-human chorionic gonadotropin (β-hCG) levels after cleavage or blastocyst embryo transfers (ET) in predicting pregnancy outcome.[Methods]A total of 2421 IVF-ET cycles in our center performed from June 2010 to May 2015 and resulted in clinical intrauterine pregnancies were analyzed retrospectively. The predictive value was compared betweenβ-hCG on day 14 after cleavage ET andβ-hCG on day 12 after blastocyst ET.[Results]Serumβ-hCG levels of patients re?sulted in clinical intrauterine pregnancies were significantly higher with blastocyst ET compared with cleavage ET. This significant dif?ference was also existed in patients resulted in miscarriage, ongoing pregnancy (OP) or live birth (LB). However, this significant differ?ence was only existed in frozen embryo transfers. For a frozen cleavage ET, the cut-off value was 475 U/L (sensitivity 79%, specificity 61.3%) in predicting LB. For a frozen blastocyst ET, the cut-off value was 575 U/L (sensitivity 74.9%, specificity 59.2%) in predicting LB.[Conclusion]In frozen embryo transfers, early serumβ-hCG level after blastocyst ET is higher than cleavage ET. The cut-off val?ue in predicting pregnancy outcome is different according to the stage embryo transferred. Early serum β-hCG can effectively predict live birth after blastocyst or cleavage ET.

Objective To analyze the genetic etiology of lateral ventriculomegaly fetal on the genome-wide level with chromosomal microarray analysis (CMA),and investigate the relationship between copy number variations (CNVs) and lateral ventriculomegaly and the application value of CMA in prenatal diagnosis of fetuses with lateral ventriculomegaly.Methods Seventy fetuses with lateral ventriculomegaly but normal or uncertain karyotype were selected and invasive prenatal diagnosis was performed in Xi Jing Hospital of the Fourth Military Medical University from Jan.2015 to Nov.2016.Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database.The fetal development was regularly inspected,and follow up was conducted to find out the pregnancy outcome and fetal postnatal conditions.Results In 70 cases of lateral ventriculomegaly fetuses,there were 9 fetuses with pathogenic copy number variations (CNVs),3 fetuses with likely pathogenic CNVs and 1 fetus with likely pathogenic 1 oss of heterozygosity (LOH).During the 70 fetuses with lateral ventriculomegaly,2 pathogenic CNVs were detected in 6 fetuses with severe and non isolated lateral ventriculomegaly (33.3％).Pathogenic CNVs was not detected but 1 likely pathogenic CNV was detected in 3 fetuses with severe and isolated lateral ventriculomegaly (33.3％).Six pathogenic CNVs were detected in 31 mild and non isolated lateral ventriculomegaly (19.4％),and 2 likely pathogenic CNVs were also detected in these group (6.5％).One pathogenic CNV and 1 likely pathogenic CNV were detected in 30 fetuses with mild and isolated fetal lateral ventriculomegaly.Conclusions CMA can identify chromosome abnormality microdeletion/microduplication which was unrecognizable by conventional karyotyping analysis.The application of CMA may increase the detection rate of pathogenic CNVs in fetuses with lateral ventriculomegaly,and benefit evaluation of fetal prognosis in prenatal genetic counselling.

OBJECTIVETo analyze the incidence and mortality of oral cavity and pharyngeal cancer in cancer-registration areas of China in 2009.

METHODSWe collected data about incidence of oral cavity and pharyngeal from 72 cancer registry sites of National Central Registry Database in 2009, covering 85 470 522 person (57 489 009 were from urban areas, 27 981 513 were from rural areas).Incidence and mortality rates, proportions, cumulative rate (0-74 years old), cut rate (35-64 years old), age-specific rate were then calculated and analyzed respectively. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population.

RESULTSThere were 2803 new diagnosed oral cavity and pharyngeal cancer cases, 1793 male and 1010 female, with the sex ratio at 1.78: 1. The crude incidence rate of oral cavity and pharyngeal cancer was 3.28/100 000(2803/85 470 522). The crude incidence rate of males was 4.15/100 000(1793/43 231 554) while it was 2.39/100 000(1010/42 238 968) among females. The age-standardized incidence rates by Chinese standard population (ASIRC) and the world standard population were 1.72/100 000 and 2.23/100 000 respectively, and the cumulative rate and cut rate was separately 0.26% and 4.02/100 000. The crude incidence and ASIRC of oral cavity and pharyngeal cancers were 3.87/100 000 (2225/57 489 009) and 1.97/100 000 in urban areas, whereas in rural areas, they were 2.07/100 000(578/27 981 513) and 1.17/100 000. There were 1172 death cases, including 825 males and 347 females. The crude mortality rate was 1.37/100 000 (1172/85 470 522), while it was 1.91/100 000(825/43 231 554) among males and 0.82/100 000(347/42 238 968) among females. The age-standardized incidence rates were 0.64/100 000 and 0.88/100 000 respectively, by Chinese standard population (ASMRC) and the world standard population. The cumulative mortality rate (0-74 age years old) and cut rate were separately 0.10% and 1.34/100 000. The mortality and ASMRC were 1.59/100 000(915/57 489 009) and 0.72/100 000 in urban areas, whereas in rural areas, they were 0.92/100 000(257/27 981 513) and 0.48/100 000 respectively.

CONCLUSIONSBoth the incidence and mortality of oral cavity and pharyngeal cancer in China were still low in 2009.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mouth Neoplasms ; epidemiology ; mortality ; Pharyngeal Neoplasms ; epidemiology ; mortality ; Rural Population ; Sex Distribution ; Survival Rate ; Urban Population ; Young Adult

Objective To explore the relationship between physical activity(PA) and the risk of colon cancer. Methods Cohort studies on physical activity and risk of colon cancer were identified by searching MEDLINE, EMBASE, Chinese Bio-medicine and Chinese Wanfang databases from January 1979 to December 2009. Results from the individual studies were synthetically combined in our study. Inverse variance weighting was used in fixed effects model and the random effects estimate was based on the DerSimonian-Laird method. Variance-weighted least squares method was used for trend test of summarized dose-response data. Results A total of 28 studies were included in our analysis. An inverse association between physical activities and the risk of colon cancer was observed with the relative risks (RR) as 0.75 [95% confidence interval (CI): 0.66-0.86] in males and 0.85(95%CI: 0.76-0.95)in females, respectively. However, the findings from those documents with high quality showed significant and borderline significant associations between PA and colon cancer in both males (RR=0.74, 95% CI: 0.61-0.90) and females (RR=0.99, 95% CI: 0.95-1.02). Meanwhile, the dose-response trend was not observed either in males (P=0.142) or in females (P=0.417). For men, the pooled RRs differed by subsites were 0.62(95%CI:0.45-0.85) and 0.74 (95%CI:0.56-0.99)for highest level PA, compared with lowest level PA in proximal colon and distal colon cancer,respectively. For women, the pooled RRs were 0.84 (95%CI: 0.69-1.01 ) in proximal colon and 0.75(95%CI: 0.53-1.05)in distal colon cancer, respectively. Conclusion These results added to the evidence for the protective effects in colon cancer among men and women.

OBJECTIVETo evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence.

METHODSA prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated.

RESULTSFrom Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits.

CONCLUSIONImatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.

Adult ; Aged ; Aged, 80 and over ; Benzamides ; Chemotherapy, Adjuvant ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Piperazines ; therapeutic use ; Postoperative Period ; Prospective Studies ; Pyrimidines ; therapeutic use ; Young Adult