ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

【Objective】 To explore the safety and efficacy of a novel endoscopic two-wire guided dilation in the creation of channels in percutaneous nephrolithotomy (PCNL). 【Methods】 Clinical records of 180 patients undergoing PCNL during Oct.2020 and Oct.2022 were retrospectively analyzed. The patients were divided into three groups, 60 in AMD group (fascial amplatz dilation), 60 in OSD group (one shot dilation) and 60 in END group (endoscopic dilation). Time to establish channels, operating time, failure of access, stone clearance rate, drop in hemoglobin, embolization rate, fever rate, blood transfusion rate and postoperative hospitalization were compared among the three groups. 【Results】 There were no significant differences in the general data among the three groups (P>0.05). Compared with AMD and OSD groups, END group needed significantly reduced time to establish the first channel [(5.6±0.8) min vs. (4.9±1.4) min vs. (4.2±0.5) min, (P<0.05)] . Compared with OSD group, END and AMD groups had significantly more hemoglobin drop [(14.0±17.6) g/L vs. (19.4±12.6) g/L vs. (10.2±6.8) g/L, (P<0.05)] . There were no significant differences in terms of failure of establishing channels, operating time, stone clearance rate, embolization rate, fever rate, blood transfusion rate and postoperative hospitality. Four patients needed selective renal artery embolization (1 case in AMD group and 3 in OSD group). No serious complications such as organ injuries, septic shock or death occurred. 【Conclusion】 Endoscopic two-wire guided dilation is simple, with few complications and good application value.

OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.

Objective:To establish quality control products for 2019-nCoV detection, and provide reliable control materials for the quality evaluations of the 2019-nCoV detection kit based on fluorescence PCR.Methods:Virus strain was diluted to concentrations of 10 6, 10 5, 10 4, 10 3, 10 2 copies/ml which were used as positive control products. The mean value, standard deviation, coefficient of variability (CV) and tendency of the Ct values were calculated. The homogeneity and stability of the quality control products were tested. Results:Within the concentration gradients, Ct value and concentration of the control products were linearly related. In homogeneity test, the CVs of the quality control products with concentrations of 10 6, 10 5, 10 4, 10 3, 10 2 and 0 copies/ml were 4.60%, 2.67%, 2.22%, 2.04% and 2.50% respectively. In stability test, there was no significant linear trend with extended test time at 4 ℃. Conclusion:Evaluations of homogeneity and stability indicated that the quality control products were established successfully. And the products can be used for evaluation of 2019-nCoV detection kit based on fluorescence PCR.

Objective:To investigate the species and concentrations of airborne pollens in Wuhan urban area and their correlation with the number of visits of allergic rhinitis patients.Methods:Retrospective analysis of pollen dispersal characteristics and the number of patients with allergic rhinitis presenting to Tongji Hospital of Huazhong University of Science and Technology in Wuhan city from October 2017 to September 2018, as well as pollen allergen testing results of patients with allergic rhinitis presenting to the Department of Allergy during the same period. Pollen data was collected by a 1-year air sampling conducted in Wuhan City during the same period using the volumetric method. The samples were examined microscopically to identify airborne pollen species and counted, and the concentrations of various pollens were calculated. Information on patients with allergic rhinitis who came to the hospital during the same period was collected, and the correlation between pollen concentration and the number of patient visits was statistically analyzed using Pearson correlation analysis.Results:A total of 35 types of airborne pollen were collected from October 2017 to September 2018. The dominant pollens in spring were Moraceae (68.46%, 1 042/1 522), Pendula (12.22%, 186/1 522) and Cupressaceae (2.30%, 35/1 522); in summer and autumn, the dominant pollens were Artemisia (3.81%, 58/1 522), Humulus (4.01%, 61/1 522) and Ambrosia (0.59%, 9/1 522). The peak number of visits for allergic rhinitis patients occurred in March-April and July-September, both exceeding 2 200 visits and reaching a maximum of 2 545 visits. There was a very weak correlation between the number of visits and the total pollen concentration ( r=0.17, P=0.001). The average monthly pollen skin prick test positive rate of patients with allergic rhinitis was highest in March-May, exceeding 40% with a maximum of 45.73%, and there was a significant correlation between the positive pollen skin prick test positive rate and the average monthly pollen concentration ( r=0.62, P=0.031). Conclusions:Pollen species and concentrations fluctuated continuously with time in Wuhan urban area, with peak pollen dispersal in spring from March to April and in autumn from August to September. The number of visits to patients with allergic rhinitis and the positive pollen skin prick test positive rate increased accordingly during the peak pollen concentration periods.

Objective:To investigate the species and concentrations of airborne pollens in Wuhan urban area and their correlation with the number of visits of allergic rhinitis patients.Methods:Retrospective analysis of pollen dispersal characteristics and the number of patients with allergic rhinitis presenting to Tongji Hospital of Huazhong University of Science and Technology in Wuhan city from October 2017 to September 2018, as well as pollen allergen testing results of patients with allergic rhinitis presenting to the Department of Allergy during the same period. Pollen data was collected by a 1-year air sampling conducted in Wuhan City during the same period using the volumetric method. The samples were examined microscopically to identify airborne pollen species and counted, and the concentrations of various pollens were calculated. Information on patients with allergic rhinitis who came to the hospital during the same period was collected, and the correlation between pollen concentration and the number of patient visits was statistically analyzed using Pearson correlation analysis.Results:A total of 35 types of airborne pollen were collected from October 2017 to September 2018. The dominant pollens in spring were Moraceae (68.46%, 1 042/1 522), Pendula (12.22%, 186/1 522) and Cupressaceae (2.30%, 35/1 522); in summer and autumn, the dominant pollens were Artemisia (3.81%, 58/1 522), Humulus (4.01%, 61/1 522) and Ambrosia (0.59%, 9/1 522). The peak number of visits for allergic rhinitis patients occurred in March-April and July-September, both exceeding 2 200 visits and reaching a maximum of 2 545 visits. There was a very weak correlation between the number of visits and the total pollen concentration ( r=0.17, P=0.001). The average monthly pollen skin prick test positive rate of patients with allergic rhinitis was highest in March-May, exceeding 40% with a maximum of 45.73%, and there was a significant correlation between the positive pollen skin prick test positive rate and the average monthly pollen concentration ( r=0.62, P=0.031). Conclusions:Pollen species and concentrations fluctuated continuously with time in Wuhan urban area, with peak pollen dispersal in spring from March to April and in autumn from August to September. The number of visits to patients with allergic rhinitis and the positive pollen skin prick test positive rate increased accordingly during the peak pollen concentration periods.

Objective:To understand the pathogenic spectrum and epidemiological characteristics of febrile respiratory syndrome in Guangdong province, and to provide reference for disease prevention, clinical diagnosis and treatment.Methods:The pathogens of 1 891 nasopharyngeal swabs collected from 2011 to 2018 were detected by real-time fluorescent polymerase chain reaction. The different rates were compared by chi-square test or Bonferronni method of comparison.Results:Among 1 891 samples, 810 samples were positive for viral nucleic acid, with a total detection rate of 42.78%. The main infectious agents were Parainfluenza virus (PIV), Rhinovirus (RhV) and Coronavirus(CoV). The pathogen detection rate was higher in <5 years group and 5~ years group. Pathogen detection in patients with different symptoms showed that the detection rate of Metapneumovirus (MPV) in pneumonia patients was relatively high. Influenza virus A (FluA), PIV, CoV and RhV had higher detection rate in patients without pneumonia. FLuA and Adenovirus (ADV)had a relatively high detection rate in the high and ultra-high fever groups. The detection rate of CoV and Mycoplasma pneumonia(MP) in moderate fever group was relatively high. The detection rate of PIV in cough patients was relatively high. The prevalence of several viruses has strong seasonality, and the detection rate was generally higher in winter and spring. Different virus detection rates also have strong regularity in years.Conclusions:PIV, RhV and CoV are the main pathogens of febrile respiratory syndrome in Guangdong in recent years.

Objective: To explore the clinical effect and safety of minor liver resection for hilar cholangiocarcinoma (HC) of Bismuth-Corlette type Ⅲ and Ⅳ. Methods: From May 2007 to May 2017, the clinical data of 108 patients with Bismuth-Corlette type Ⅲ and Ⅳ HC underwent hepatectomy were collected and analyzed retrospectively.There were 56 males and 52 females, aged (57.2±5.3) years (ranged 48-76 years) .Among the 108 cases, there were 51 cases of type Ⅲa, 40 cases of type Ⅲb and 17 cases of type Ⅳ. Small-scale hepatectomy (≤3 hepatectomy) was performed in 70 cases, including 8 cases of 4b segment resection, 28 cases of 4b segment+5 segment resection, and 34 cases of partial 4 segment+partial 7 segment+partial 1 segment resection. Large-scale hepatectomy was performed in 38 cases (>3 segments) , of which 30 cases were treated with 2 segments+3 segments+4 segments+1 segment, and 8 cases were treated with 5 segments+7 segments+8 segments+1 segment. t′ test was used to analyze the data which did not conform to the normal distribution, and χ² test was used to calculate the incidence of postoperative complications and the 1, 3, and 5-year cumulative overall survival rate. Results: (1) The operation time of minor liver resection group ((180±25)minutes) was shorter than that of major liver resection group ((210±35)minutes) (t′=4.676, P<0.05) , the amount of blooding operation time of minor liver resection group ((310±80)ml) was less than that of major liver resection group ((500±110)ml)in the operation (t′=9.385, P<0.05) , and the difference was statistically significant. (2) The incidence of complications was lower in minor liver resection group and major liver resection group, and the difference was statistically significant (χ²=5.230, P<0.05) . (3) The actual 1-, 3- and 5-year survival rates were 87.1%, 58.4%, 30.0% and 84.2%, 57.9%,31.6%, respectively. There were no significant differences in survival rates in two groups in 1-, 3- and 5-year survival rates (χ²=0.177, P=0.674; χ²=0.005, P=0.946; χ²=0.029, P=0.865) . Conclusions Compared to patients with major liver resection, Minor liver resection for selected patients with HC of Bismuth-Corlette Ⅲ and Ⅳaccording to our criteria achieved better long-term outcomes. Chen′s biliojejunostomy is a simple, effective and safe method, which can be widely used when there are multiple biliary intestinal anastomosese.