Effect of Toll-like receptor 4 deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in a murine model of experimental autoimmune neuritis.

Introduction: The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN). Material and methods: We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180-199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund's incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit. Results: We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts. Conclusions: Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

Identification of common genetic polymorphisms associated with down-regulated gonadotropin levels in an exome-wide association study.

OBJECTIVE: To investigate whether common genetic polymorphisms are associated with gonadotropin levels after down-regulation with daily gonadotropin-releasing hormone agonist and whether the polymorphisms of candidate variants influence the ovarian response to exogenous gonadotropins. DESIGN: Genetic association study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Subjects enrolled in an exploratory exome-wide association study (n = 862), a replication exome-wide association study (n = 86), and a classifier validation study (n = 148) were recruited from September 2016 to October 2018, September 2019 to September 2020, and January 2021 to December 2021, respectively. The included patients were aged ≤40 years and had a basal follicle-stimulating hormone (FSH) ≤12 IU/L. INTERVENTIONS: All participants received a luteal phase down-regulation long protocol. Genome DNA was extracted from the peripheral blood leukocytes. For the exploratory and replication cohorts, exome sequencing was conducted on a HiSeq 2500 sequencing platform. The multiplex polymerase chain reaction amplification technique and next-generation sequencing also were performed in the exploratory and replication cohorts. For the samples of the validation cohort, Sanger sequencing was performed. MAIN OUTCOME MEASURES: The primary endpoint was the gonadotropin levels after down-regulation, and the secondary endpoints were hormone levels and follicle diameters during stimulation, the total dose of FSH, duration of FSH stimulation, number of oocytes retrieved, and clinical pregnancy rate. RESULTS: In the exploratory cohort, we identified that FSHB rs6169 (P=2.71 × 10-24) and its single-nucleotide polymorphisms in high linkage disequilibrium were associated with the down-regulated FSH level. The same locus was confirmed in the replication cohort. Women carrying the C allele of FSHB rs6169 exhibited higher average estradiol level during stimulation (P=6.82 × 10-5), shorter duration of stimulation, and less amount of exogenous FSH (Pduration=0.0002; Pdose=0.0024). In the independent validation set, adding rs6169 genotypes into the prediction model for FSH level after down-regulation enhanced the area under the curve from 0.560 to 0.712 in a logistic regression model, and increased prediction accuracy by 41.05% when a support vector machine classifier was applied. CONCLUSION: The C allele of FSHB rs6169 is a susceptibility site for the relatively high level of FSH after down-regulation, which may be associated with increased ovarian FSH sensitivity.

Observation on the clinical outcomes of continued pregnancy following cesarean scar pregnancy in 55 women / 中华妇产科杂志

Objective:To observe the clinical outcomes of continued pregnancy in pregnant women with cesarean scar pregnancy (CSP).Methods:A retrospective analysis was performed on the pregnancy outcomes of 55 pregnant women who were diagnosed with CSP at the Second Affiliated Hospital of Army Medical University during the first trimester of pregnancy from August 1st, 2018 to October 31st, 2021 and strongly requested to continue the pregnancy.Results:Of the 55 pregnant women, 15 terminated the pregnancy in the first trimester, 1 underwent hysterotomy at 23 weeks of gestation due to cervical dilation, and 39 (71%, 39/55) continued pregnancy to the third trimester achieving live births via cesarean section. The gestational age of the 39 pregnant women delivered by cesarean section was 35 +6 weeks (range: 28 +5-39 +2 weeks), of whom 7 cases at 28 +5-33 +6 weeks, 20 cases at 34-36 +6 weeks, and 12 cases at 37-39 +2 weeks. The results of pathological examination were normal placenta in 3 cases (8%, 3/39), placenta creta in 4 cases (10%, 4/39), placenta increta in 9 cases (23%, 9/39) and placenta percreta in 23 cases (59%, 23/39). Among the 36 pregnant women who were pathologically confirmed as placenta accreta spectrum disorders (PAS) after surgery, the last prenatal ultrasonography showed placenta previa in 27 cases (75%, 27/36) and not observed placenta previa in 9 cases. The median intraoperative blood loss, autologous blood transfusion, and allogeneic suspended red blood cell infusion of 39 pregnant women during cesarean section were 1 000 ml (300-3 500 ml), 300 ml (0-2 000 ml) and 400 ml (0-2 400 ml), respectively. The uterine preservation rate was 100% (39/39), and only 1 case received cystostomy due to intracystic hemorrhage. The birth weight of the newborn was 2 580 g (1 350-3 800 g), and 1 case of mild asphyxia. Conclusions:Pregnant women with CSP who continue pregnancy under close monitoring after adequate ultrasound evaluation and doctor-patient communication could achieve better maternal and infant outcomes, but pregnant women with CSP are highly likely to continue pregnancy and develop into PAS. Effective hemostasis means and multidisciplinary team cooperation are needed in perinatal period for ensuring maternal and fetal safety.

Novel biomarkers of sepsis-associated acute respiratory distress syndrome / 中国小儿急救医学

Acute respiratory distress syndrome(ARDS)is one of the most common complications of sepsis, resulting in the high risk of death in patients with sepsis.By comparison with non-septic ARDS, sepsis-associated ARDS is characterized by high morbidity, heterogeneity and mortality.It is vital to early identify the occurrence of ARDS, accurately assess the severity, as well as effectively implement the individualized treatment.Based on the genome-wide association study, mass cytometry, and multiple omics data analysis, the molecular signatures of sepsis-associated ARDS have been elucidated, which were related to genetic susceptibility, inflammatory reaction pathway, and metabolic characteristics.The development of novel biomarkers is helpful to molecular classifier, risk stratification, early recognition and assessing severity, implement early intervention, then improving the prognosis.

6-Formylindolo3,2-bcarbazole alleviates lipopolysaccharide-induced acute lung injury via suppressing endoplasmic reticulum stress / 中华危重病急救医学

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Transmissibility of coronavirus disease 2019 (COVID-19) in Chinese cities with different transmission dynamics of imported cases

BackgroundMonitoring the time-varying reproduction number (Rt) of the disease is useful in determining whether there is sustained transmission in a population. In this study, we examined Rt of COVID-19 and compared its transmissibility between different intervention periods in Hangzhou and Shenzhen. MethodsDaily aggregated counts of confirmed imported and local cases between January 1, 2020 and March 13, 2020 were analysed. A likelihood function was constructed to estimate Rt, accounting for imported cases. ResultsAlthough Hangzhou had fewer number of cases than Shenzhen, Shenzhen had higher proportion of imported cases than Hangzhou (83% vs 29%). Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was kept below unity through time. On the contrary, Rt was greater than unity in Hangzhou from 16 January to 7 February due to the surge in local cases. Credits to the Wuhan lockdown and outbreak response measures following the local lockdown, Rt decreased steadily and dropped below unity in mid-February. ConclusionThe lockdown measures and local outbreak responses helped reduce the potential of local transmission in Hangzhou and Shenzhen. Meanwhile, cities with similar epidemic trend could have different transmission dynamics given the variation in imported cases.

Monitoring Disease Transmissibility of 2019 Novel Coronavirus Disease in Zhejiang, China

We monitored the transmissibility of 2019 novel coronavirus disease in Zhejiang accounting the transmissions from imported cases. Even though Zhejiang is one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers <1) was observed in early/mid-February after an early social-distancing response to the outbreak.

A Rare High-Grade Glioma with a Histone H3 K27M Mutation in the Hypothalamus of an Adult Patient.

BACKGROUND: Diffuse midline glioma H3 K27M mutant is a new tumor entity described in the revised 2016 World Health Organization classification. It is most frequently observed in children and develops in midline structures, including the brainstem, thalamus, and spine. We describe a rare diffuse midline glioma with an H3 K27M mutation arising in the hypothalamus of an adult. CASE DESCRIPTION: A 27-year-old woman was admitted to our department complaining of amenorrhea, polydipsia, and diuresis for the previous 3 months, and headache and lethargy for approximately 10 days. Computed tomography scan showed an oval isodense solid mass extending from the pituitary toward the suprasellar cistern. A gadolinium-enhanced magnetic resonance imaging (MRI) showed a strongly heterogeneous enhanced solid lesion and nonenhanced cystic lesion. The patient underwent surgery and chemoradiotherapy with temozolomide. Histologic and immunohistochemical analyses revealed H3 K27M-mutant diffuse midline glioma. The patient underwent another resection for a recurrent tumor 5 months after the first surgery. Three months after the second operation, the patient relapsed, with MRI revealing spinal cord and meningeal metastases; she died shortly afterward. CONCLUSIONS: Diffuse midline glioma with an H3 K27M mutation occurring in the hypothalamus of an adult is rare but should be considered in differential diagnoses. Because histone H3 K27M mutations are associated with aggressive clinical behavior and poor prognosis, molecular analyses should be used to determine the clinical and histopathologic features of such tumors. This will contribute to developing targeted drugs and gene therapy going forward.

Association of PTTG1 polymorphism rs1895320, rs2910200 and rs6882742 with non-functioning pituitary adenomas in Chinese Han population: a case-control study.

Due to absence of clinical manifestations of hormonal hyper secretion, the treatment of Nonfunctioning pituitary adenoma (NFPA) was always delayed. PTTG1 was reported to be overexpressed in most of pituitary tumors, however, the polymorphism of PTTG1 rs1895320, rs2910200 and rs6882742 with NFPA were still not fully elucidated in NFPA. Thus, a hospital based case control study which included 79 patients and 142 healthy control participants were conducted. DNA was extracted from peripheral blood samples and genotyped by Mass Array methods. In addition, a meta-analysis of rs2910200 was also employed to further testify the conclusion. Significant difference were observed between patients and healthy controls under rs2910200 locus between allelic genotype (p = 0.0219). However, no other significant difference was observed in rs1895329 and rs6882742. In addition, a logistic regression analysis showed that the dominant model of rs2910200 were closely correlated with the NFPA susceptibility (OR = 1.951, 95% CI:1.075-3.542, p = 0.028). While no significant difference was observed in the rs1895320 and rs6882742 under dominant model, recessive model and additive model The meta-analysis results showed that the dominant model and heterozygote model can significantly increase the risk of PA (p = 0.007, OR = 1.57, 95% CI:1.14-2.18; p = 0.009, OR = 1.57, 95% CI:1.12-2.19). Whereas no significant difference were observed under the homozygous model and recessive model. In conclusion, the polymorphism of PTTG1 rs2910200 dominant model and T allelic might increase the risk of NFPA.

Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway / 中华急诊医学杂志

Objective To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups:control group (control),LPS-induced endotoxemia model (LPS),only methylprednisolone (MP) administration group (MP),and intervention group with 2 mg/kg MP (LPS+MP) (n=8 per group).The wet/dry (W/D) weight ratio of lung tissue,lung pathology by hematoxylin & eosin (HE) staining,serum and mRNA levels of TNF-α and IL-6 in lungs were determined.The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot.Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.Results (1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17),P =0.038];(2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening;(3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±l.64) pg/mL vs (6.61±1.27) pg/mL,P =0.003;(1.42±0.35) pg/mL vs (3.80±1.35) pg/mL,P =0.008,respectively],and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05),P =0.03;(1.62±1.00) vs (11.12±6.56),P=0.026;respectively];(4)MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06),P ＜0.001,(0.24±0.02) vs (1.34±0.32),P ＜ 0.001].Conclusions Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.

Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway / 中华急诊医学杂志

Objective@#To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).@*Methods@#The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.@*Results@#(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001].@*Conclusions@#Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.

Assessment of the Influence on Spontaneous Pregnancy of Hysterosalpingo-Contrast Sonography.

OBJECTIVE: Our objective was to explore whether the pregnancy rate (PR) was higher than usual after hysterosalpingo-contrast sonography (HyCoSy). METHODS: We conducted a prospective observational study of 1,008 infertility patients, all of whom were examined by HyCoSy. The expected time for spontaneous pregnancy was at least 180 days after the HyCoSy exams. There were three types of HyCoSy results: type I, defined as both fallopian tubes patent; type II, defined as one fallopian tube patent with obstruction in the other; and type III, defined as both fallopian tubes obstructed. During the HyCoSy examinations, we recorded the mobility of the ovaries, injective resistance, and contrast agent venous intravasation. Before the examinations, we recorded each patient's medical history, including maternal age, infertility type, median duration of menstrual cycle, dysmenorrhea, and parity number. RESULTS: The PR was 19.44% within 180 days after HyCoSy and it was significantly higher in the first 30 days (6.35%) (P <.01). The PR of type I was highest, with a rate of 32.01%, followed by the PR of type II (25.51%) and type III (15.04%) (P <.01). Univariate analysis showed that younger age, patency of both fallopian tubes, good ovarian mobility, and absence of injective resistance were positively related to the initiation of pregnancy (P <.01). Infertility type, median duration of menstrual cycle, dysmenorrhea, parity number, contrast agent venous intravasation, and identity of the sonographer were unrelated to pregnancy (P >.05). However, multivariate analysis showed that patency of both fallopian tubes and the absence of injective resistance were independently associated with pregnancy. CONCLUSION: Some infertility patients conceived successfully and naturally not long after HyCoSy, most often in the first month after the examination. Multivariate analysis showed that patency of both fallopian tubes and the absence of injective resistance were independently factors associated with the ability to conceive after HyCoSy examination.

A Randomized Controlled Trial of Chinese Patent Medicine Xiao'er Biantong Granules in the Treatment of Functional Constipation in Children.

OBJECTIVE: To confirm the effect and safety of Xiao'er Biantong (XEBT) granules for treating chronic constipation in children. METHODS: This randomized, double-blind, multicenter study enrolled 480 children with age of 1-14 years who had FC. All of them were randomly assigned to receive either XEBT granules or its placebo in the ratio of 3 : 1. The primary efficacy outcome was the frequency of spontaneous bowel movements (SBM) for 14 days, and secondary outcomes were effectual time, score of main symptoms, effect of constipation, disappearance rate of accompanying symptoms, and recurrence rate. We also observed the adverse event (AE) and adverse drug reaction (ADR) to evaluate safety. RESULTS: The sociodemographic characteristics and efficiency data were comparable in the two groups at baseline. The mean values of SBM for 14 days were 8.89 and 5.63 in the XEBT group and the placebo group, respectively, and there were 86.87% and 30.91% subjects in two groups up to SBM ≥ 3/week, respectively. There were significant differences between the two groups. The effects in the XEBT group on median effectual time of defecation, main symptom score, disappearance rate of symptoms, and the differences were significant. The conclusions based on full analysis set (FAS) and per protocol set (PPS) were consistent. Nine AEs were reported, of which 7 were in the XEBT group (2.02%) while 2 were in the placebo group (1.77%). There were no significant differences in the occurrence rate of AE and ADR between the two groups. CONCLUSIONS: Xiao'er Biantong granules have superior efficacy compared to the placebo for the treatment of functional constipation in children and are well tolerated.

Corrigendum to "A Randomized Controlled Trial of Chinese Patent Medicine Xiao'er Biantong Granules in the Treatment of Functional Constipation in Children".

[This corrects the article DOI: 10.1155/2018/4941505.].

Stems and leaves of Aconitum carmichaelii Debx. as potential herbal resources for treating rheumatoid arthritis: Chemical analysis, toxicity and activity evaluation / 中国天然药物

According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.

Stems and leaves of Aconitum carmichaelii Debx. as potential herbal resources for treating rheumatoid arthritis: Chemical analysis, toxicity and activity evaluation / 中国天然药物

According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.

Heart-type fatty acid-binding protein predict the prognosis in pediatric patients with sepsis and septic shock / 中华急诊医学杂志

Objective To investigate the prognostic value of heart-type fatty acid-binding protein (H-FABP)in pediatric patients with severe sepsis and septic shock. Methods A prospective observational study was carried out in consecutive pediatric patients with severe sepsis and septic shock admitted between October 2016 and September 2017. Data of patient's demographics, clinical characteristics, blood biochemical markers including H-FABP, N-terminal B-type natriuretic peptide (NT-BNP), creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTnl), Lactate dehydrogenase (LDH) and Lactic acid (Lac), complications and survival status were collected and analyzed. The receiver operating characteristic (ROC) curve was mainly used to evaluate the power of a continuous variable for 28-day survival rate, and Kaplan-Meier analysis was used to compare 28-day survival curves in pediatric patients with severe sepsis and septic shock. Results A total of 78 cases with severe sepsis (n=33) and septic shock (n=45) were enrolled in this study. There were 64 survival cases and 14 non-survivor within 28 days after admission. The plasma levels of H-FABP, NT-BNP, LDH, CK-MB were significantly higher in non-survivor than those in survivor (49.10±65.14) vs. (5.06±4.29) ng/ml; (131.63±130.91) vs. (37.30±29.24) U/L; (2 403.88±415.97) vs.(2 971.57±279.49) U/L; (5 872.93±6 383.28)pg/ml vs. (1 656.86±2 715.73) pg/ml; respectively, all P＜0.05). The area under the receiver operating characteristic curve (AUC) of H-FABP was 0.858 (95％ confidence interval [CI]: 0.716-1.0; P=0.002), which was superior to CK-MB (AUC=0.841,95％CI: 0.696-0.986; P=0.003);LDH (AUC=0.818, 95％CI: 0.610-1.000; P =0.005) and NT-BNP (AUC=0.728, 95％CI: 0.535-0.921;P=0.045). A Kaplan-Meier curve showed a significantly lower survival rate in patients with H-FABP greater than 7.7 ng/mL than the patients with H-FABP less than 7.7 ng/mL. Conclusions H-FABP is an effective prognostic indicator in pediatric patients with severe sepsis and septic shock with superiority to traditional myocardial enzyme.

A novel quantified bitterness evaluation model for traditional Chinese herbs based on an animal ethology principle

Traditional Chinese herbs (TCH) are currently gaining attention in disease prevention and health care plans. However, their general bitter taste hinders their use. Despite the development of a variety of taste evaluation methods, it is still a major challenge to establish a quantitative detection technique that is objective, authentic and sensitive. Based on the two-bottle preference test (TBP), we proposed a novel quantitative strategy using a standardized animal test and a unified quantitative benchmark. To reduce the difference of results, the methodology of TBP was optimized. The relationship between the concentration of quinine and animal preference index (PI) was obtained. Then the PI of TCH was measured through TBP, and bitterness results were converted into a unified numerical system using the relationship of concentration and PI. To verify the authenticity and sensitivity of quantified results, human sensory testing and electronic tongue testing were applied. The quantified results showed a good discrimination ability. For example, the bitterness of Coptidis Rhizoma was equal to 0.0579 mg/mL quinine, and Nelumbinis Folium was equal to 0.0001 mg/mL. The validation results proved that the new assessment method for TCH was objective and reliable. In conclusion, this study provides an option for the quantification of bitterness and the evaluation of taste masking effects.

Systematic review and comment on modern study of Xiaojin Pills / 中国中药杂志

Xiaojin Pill, was firstly recorded in Life-saving Manual of Diagnosis and Treatment of External Diseases, with its primitive name of "Xiaojin Dan". Xiaojin Pill is a classic prescription for treating carbuncle and it is the first choice for Chinese medicine in the clinical treatment of hyperplasia of mammary glands. In this paper, the literature reports on Xiaojin Pills were summarized and the historical evolution, material basis, pharmacological action, quality control and other problems were systematically discussed to explore the potential problems in every aspect of the development status, and put forward the development countermeasures, providing reference for the modernization research and development of Xiaojin Pills.

In Silico System Pharmacology for the Potential Bioactive Ingredients Contained in Xingnaojing Injection () and Its Material Basis for Sepsis Treatment / 中国结合医学杂志

OBJECTIVE@#To elucidate the action mechanism of Xingnaojing Injection (, XNJI) for sepsis, and to target screen the potential bioactive ingredients.@*METHODS@#An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-lipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction.@*RESULTS@#Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment.@*CONCLUSIONS@#The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.