By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

Objective:To investigate the clinical and genetic characteristics of a child with microcephaly-capillary malformation syndrome due to a STAMBP mutation. Methods:The clinical data of a case of microcephaly-capillary malformation syndrome caused by STAMBP gene mutation admitted to Anhui Children′s Hospital in August 2023 were collected. The genes of the child and his parents were detected by whole exome sequencing, and the risk was predicted by biological software. At the same time, the clinical characteristics of the child were analyzed and the literature was reviewed. Results:The patient is a male child aged 2 years and 7 months. The patient had special features, microcephaly, refractory epilepsy, severe comprehensive developmental delay, and capillary malformations. The results of genetic testing showed that the STAMBP gene in the child had complex heterozygous mutations NM_001353967: c.367delG[p.E123fs *27(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp)], inherited from his mother and father respectively. The mutations have not been recorded in the HGMD, dbSNP and gnomAD databases,etc. The protein structure of the STAMBP gene was modeled that predicted c.367del(p.Glu123Lysfs *27) and c.159A>C (p.Glu53Asp) had a negative effect on the function of STAMBP protein. Conclusion:The STAMBP gene complex heterozygous mutations c.367delG(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp) may be the pathogenic factor of this child, which further expands the variation spectrum of the STAMBP gene and the genotype of microcephaly-capillary malformation syndrome, and provides guidance for family genetic counseling.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

The multiple systemic symptoms appearing during the convalescence of novel coronavirus infection(COVID-19)are called long-term symptoms after COVID-19,also named as long COVID.Traditional Chinese medicine(TCM)has unique advantages in the treatment of long COVID.In the view of Professor ZHANG Zhong-De,the novel coronavirus infection belongs to the category of damp-toxin pestilence in TCM.During the convalescence of novel coronavirus infection,the damp-toxin pathogen causes the dysfunction of qi,blood,yin and yang of zang-fu organs,and then results in the consumption of yang qi or the depletion of fluid and blood.Damp-turbidity obstructing qi movement and entering collaterals and then developing into blood stasis is the key pathogenesis of long COVID.Therefore,the therapeutic principle of harmonizing yin,yang,qi and blood of the five zang-organs is proposed,and the methods for transporting and transforming damp-toxin and phlegm-turbidity,regulating qi,activating blood and removing stasis should be adopted.According to the exuberance or decline of qi,blood and body fluid,and yin and yang of the five zang-organs,the Fuzheng Series Formulas(series formulas for supporting healthy qi)were recommended for the specific syndrome types:Fuzheng Shengbai Formula can be used for the syndrome of deficiency of original qi;Fuzheng Yifei Formula can be used for lung-spleen-kidney deficiency syndrome;Fuzheng Anshen Formula can be used for the syndrome of liver qi stagnation and heart-spleen deficiency.During the treatment,Professor ZHANG Zhong-De makes the modification of drugs indicated for the retention sites of damp-toxin and turbid qi,and addresses the importance of spleen and stomach in the whole treatment process by protecting spleen and stomach,so as to promote the rehabilitation of patients after novel coronavirus infection and improve their quality of life.

Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm＞the anterior superior iliac spine(43.83±7.58)mm＞the femoral artery(38.35±6.63)mm＞the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm＞the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm＞femoral artery(33.76±6.33)mm＞femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm＞lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.

Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1％formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62％-101.24％.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.