A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns / 中华烧伤杂志

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Research progress of endothelial-to-mesenchymal transition in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Endothelial-to-mesenchymal transition(EndoMT)is a change in the transformation or differentiation of endothelial cells into mesenchymal cells under physiological or pathological conditions, accompanied by changes in phenotype and function, and is an important part of fiber repair. It is widely involved in the pathophysiological process of embryonic development, tumor invasion and a variety of fibrotic diseases. Research on the role of EndoMT in ocular diseases has also made some progress. This article will review the basic biological characteristics, mechanism and research results of EndoMT in ophthalmological diseases, intending to theoretically reveal its possibility as a treatment target and a key point of regenerative medicine technology in related diseases, provide a reference for clinical practice and scientific research.

Effect of Zuoguiwan on Wnt/β-catenin Signaling Pathway in Ovariectomized Osteoporosis Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/<italic>β</italic>-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg^-1·d^-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg^-1·d^-1）.After successful establishment of the model in the 13^th week， intragastric administration （<italic>ig</italic>） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E₂） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，<italic>β</italic>-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3<italic>β</italic>（GSK-3<italic>β</italic>） in rat tibia. Result:Compared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（<italic>P</italic><0.01）， the contents of E₂ and PINP in serum decreased significantly（<italic>P</italic><0.01）， the content of BALP，BGP，TRAP increased significantly（<italic>P</italic><0.01）， the expression levels of Wnt2，p-GSK-3<italic>β </italic>Ser9，LRP5 and <italic>β</italic>-catenin protein in bone tissue decreased significantly（<italic>P</italic><0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the contents of serum E₂ and PINP were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the content of BALP，BGP，TRAP was significantly decreased （<italic>P</italic><0.01）， and the expression level of Wnt2，p-GSK-3<italic>β</italic> Ser9，LRP5， <italic>β</italic>-catenin protein in bone tissue was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/<italic>β</italic>-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3<italic>β</italic>， reducing the degradation of <italic>β</italic>-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.

Clinical Observation of Suanzaoren Tang Combined with Fluoxetine in Treatment of Depression of Liver Stagnation and Blood Deficiency Accompanied by Insomnia / 中国实验方剂学杂志

Objective:To observe the clinical therapeutic effect of Suanzaoren Tang combined with fluoxetine in the treatment of patients with depression of liver stagnation and blood deficiency accompanied by insomnia. Method:The patients with depression of liver stagnation and blood deficiency accompanied by insomnia （120 cases） were randomly divided into an observation group and a control group， with 60 cases in each group. The patients in the observation group received Suanzaoren Tang combined with fluoxetine， and those in the control group received fluoxetine. The course of treatment was eight weeks. The clinical efficacy was evaluated with Hamilton Depression Rating Scale （HAMD）， Pittsburgh Sleep Quality Index（PSQI）， and Activities of Daily Living （ADL） score. Enzyme-linked immunosorbent assay （ELISA） was used to determine the plasma levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE），brain-derived neurotrophic factor （BDNF）， glial cell-derived neurotrophic factor （GDNF）， neuron-specific enolase （NSE）， and S100<italic>β</italic>. Result:After eight weeks of treatment， the scores of HAMD and PSQI were reduced（<italic>P</italic><0.01）， while the scores of ADL were elevated（<italic>P</italic><0.01），and the levels of 5-HT， NE， GDNF and BDNF were up-regulated （<italic>P</italic><0.01） in the plasma of patients in the observation group as compared with those before treatment. After treatment， compared with the control group， the observation group showed increased total effective rate（<italic>P</italic><0.01）， decreased scores of HAMD and PSQI （<italic>P</italic><0.01）， elevated score of ADL（<italic>P</italic><0.01）， up-regulated levels of 5-HT， NE， GDNF and BDNF in plasma， and declining NSE and S100<italic>β</italic>（<italic>P</italic><0.01）. Conclusion:Suanzaoren Tang combined with fluoxetine is superior to fluoxetine alone in treating the depression of liver stagnation and blood deficiency accompanied by insomnia. Its therapeutic effect is achieved by increasing the release of monoamine neurotransmitters and promoting the secretion of BDNF and GDNF in the brain.

Effect of Sinisan on BDNF/TrkB， 5-HT/5-HT1AR， and HPA axis in Depression Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg^-1） group， and low- （1.25 g·kg^-1）， medium- （2.5 g·kg^-1）， and high-dose （5 g·kg^-1） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.

Immunoregulatory Effect of Chaihu Jia Longgu Mulitang Modified with Bupleuri Radix on Hippocampal NLRP3 Pathway in Depressed Rats / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Chaihu Jia Longgu Mulitang （CJLM） on hippocampal NOD-like receptor protein 3 （NLRP3）inflammasome pathway in rats with depression. Method:Sixty male SD rats were randomly divided into a normal group，a model group， a MCC950 （1 mg·kg^-1） group， and high- （13 g·kg^-1）， medium- （6.5 g·kg^-1）， and low-dose （3.25 g·kg^-1） Chaihu Jia Longgu Mulitang groups， with 10 rats in each group．The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group. Rats were treated correspondingly for 21 days by intraperitoneal injection in the MCC950 group and gavage in other groups. The normal group and the model group received an equal volume of normal saline. The depression-like behaviors of rats were observed by sucrose preference test （SPT） and novelty-suppressed feeding test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>） and IL-18 in the hippocampus of depressed rats. Western blot was used to detect the protein levels of NLRP3， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， and Caspase-1. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， prolonged novelty-suppressed feeding time （<italic>P</italic><0.01）， enhanced protein expression of NLRP3，ASC， and caspase-1<italic> </italic>（<italic>P</italic><0.05， <italic>P</italic><0.01）， and elevated expression of IL-1<italic>β</italic> and IL-18 （<italic>P</italic><0.01）. Conclusion:CJLM can alleviate depression-like behaviors in CUMS-induced model rats， and the underlying mechanism is related to the inhibition of the NLRP3 inflammasome pathway．

Action Mechanisms of Zhongjing's Antidepressant Prescriptions： A Review / 中国实验方剂学杂志

Depression is a threat to human health due to high incidence， recurrence， and disability rates. At present， the complex etiology and pathogenesis of depression are still unclear， and such hypotheses as monoamine neurotransmitters and their receptor abnormality， hyperactivity of hypothalamic-pituitary-adrenal （HPA） axis， inflammation， and neuron damage and remodeling have been put forward. Anti-depressants developed based on the pathogenesis have a certain effect， but there also exist some problems like low cure rate， poor compliance， relapse after discontinuation， and obvious side effects. According to Zhongjing's theory， depression falls into the categories of depression syndrome， visceral agitation， insomnia， and lily disease， and it is mainly located in the liver， involving the spleen， heart， and kidney. The pathogenesis mainly lies in qi stagnation and zang-fu organ dysfunction. Attention should be focused on regulating qi and relieving depression. Zhongjing's antidepressant prescriptions have exhibited good clinical efficacy in the treatment of depression， reflecting the multi-pathway action advantages of Chinese herbs. Based on the pathogenesis of depression and domestic and foreign literature on the intervention of depression with Zhongjing's prescriptions available in the past 20 years， this paper summarized the mechanisms of Zhongjing's prescriptions against depression from the experimental and clinical research aspects， in order to provide reference for clinical treatment of depression with Zhongjing's prescriptions.

Mechanism of Modified Erchentang on Expression of CXCL8-CXCR1/2 Axle Genes in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup（10 g·kg-1），and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8，CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.

Regulatory Effect of Modified Erchentang on Levels of Lymphokines Relating to Th1,Th2 and Th9 Cells and Expressions of IL-4R1/IL-13RA1 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.

Research Progress of Banxia Houpu Tang in Treatment of Depression / 中国实验方剂学杂志

Depression is a common emotional disease，causing a heavy burden of disease on patients' families and society.Its pathogenesis is not yet fully understood，andmay be related to inflammation，neurotransmitters，neurotrophicfactors，hippocampal neuronal synaptic plasticity，oxidative stress，etc.Clinical application of Western medicine to treat depression has serious side effects，poor patient compliance，the effective rate is not high，rebound after withdrawal，etc.Traditional Chinese medicine treatment of depression has the characteristics of low side effects and high patient compliance. Depression belongs to the category of depression syndromein traditional Chinese medicine.Traditional Chinese medicine believes that the main symptoms of depression include depressed liver Qi，stagnated Qi transforming into fire，deficiency in heart and spleen，deficiency in heart and lung，stagnation of phlegm and Qi，deficiency of liver and kidney，etc. Banxia Houpu Tang is a classic recipe contained in"Synopsis of the Golden Chamber" by Zhang Zhongjing in the Han Dynasty， it has the effect of treating depression syndrome of stagnation of phlegm and Qi.By searching the literatures of Banxia Houpu Tang in the treatment of depression in Chinese knowledge network database （CNKI），Chinese biomedical literature database （CBM）， Wanfang Data， Pubmed， Embase， Web of Science and other databases，we found that both clinical application and experimental research suggest that Banxia Houpu Tang has a significant antidepressant effect. Clinical studies have shown that Banxia Houpu Tang can improve the scores of anxiety scales and depression scales of patients with depression. The antidepressant effect is significant， and the advantages are prominent. Experimental research shows that the antidepressant effect of Banxia Houpu Tang and its effective components may be related to the factors such as intervention of inflammatory response， influence of neurotransmitters， regulation of neurotrophic factors， improvement of synaptic plasticity of hippocampal neurons and reduce oxidative stress，etc. Therefore，this paper reviews several types of depression in the clinical treatment of Banxia Houpu Tang and the related experimental studies of Banxia Houpu Tang.

Effect of Modified Xiao Chaihutang on Expression of EAATs and VGLUTs in Hippocampus of Chronic Restraibt Stress Depression Model Rat / 中国实验方剂学杂志

Objective:To study the effect of modified Xiao Chaihutang on the expressions of excitatory amino acid transporters（EAATs） and vesicle glutamate transporters（VGLUTs）in hippocampus of rats with chronic depression， in order to explore the anti-depressant mechanism of modified Xiao Chaihutang based on glutamate transport. Method:A total of 120 SD rats were randomly divided into normal group， model group， and low， middle and high-dose modified Xiaochaihutang groups （6.5， 13， 26 g·kg-1） and riluzole group， with 20 rats in each group．Except normal group， the depression model of rats was prepared through Chronic restraint stress（CRS）. The normal group and the model group were intragastrically （ig） given normal saline. The modified Xiao Chaihutang groups were intragastrically given corresponding herbal drugs （6.5， 13， 26 g·kg-1）， and the Riluzole group was given Riluzole 20 mg·kg-1 through intraoeritoneal injection for 21 days， once a day. Then the depressive behaviors of rats were observed by forced swimming test （FST） and tail suspension test （TST）. The level of glutamic acid （Glu） in rats hippocampus was determined by high performance liquid chromatography （HPLC）. The mRNA expressions of EAAT1， EAAT2 and EAAT3 in hippocampus were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）method. Western blot was used to detect the protein expressions of EAAT1， EAAT2， EAAT3， VGLUT1 and VGLUT2 in rat hippocampus tissue. Nissl staining was used to observe the morphology of hippocampal neurons in rats. Immunohistochemical（IHC）S-P method were used to detect the location expressions of EAAT1， EAAT2 and NeuN proteins in rat hippocampal CA1 region tissue. Result:The immobility times in FST and TST were increased significantly（P<0.01）， the mRNA and protein expressions of EAAT1，EAAT2，EAAT3 were decreased significantly （P<0.01）， and as well as the expressions of VGLUT1 and NeuN were decreased significantly（P<0.01）， while the level of Glutamate and the expression of VGLUT2 were increased significantly（P<0.01） in model group， compared with normal group. Compared with model group，the immobility times in FST and TST were decreased significantly（P<0.05， P<0.01）， mRNA and protein expressions of EAAT1，EAAT2，EAAT3 were increased significantly（P<0.01）， and expressions of VGLUT1 and NeuN were increased significantly（P<0.01）. However， the level of Glutamate and the expression of VGLUT2 were decreased significantly（P<0.01）， and the damage of hippocampal neurons in rats was mild in middle and high-dose modified Xiao Chaihutang groups. Conclusion:Modified Xiao Chaihutang has an anti-depressive effect. Its mechanism may be related to its up-regulation of expressions of EAAT1， EAAT2， EAAT3 genes and VGLUT1 protein in the hippocampus of depression model rats.

Effect of Modified Suanzaoren Tang on Expression of Glutamate Receptor in Hippocampus of Chronic Restraibt Stress Depression Model Rat / 中国实验方剂学杂志

Objective:To study the effect of modified Suanzaoren Tang on the expression of excitatory amino acids receptor（EAARs） in hippocampus of rats with chronic depression， and to explore the anti-depressant mechanism of modified Suanzaoren Tang based on excitatory amino acids receptor. Method:Sixty SD rats were randomly divided into normal group，model group，and low，middle and high-dose modified Suanzaoren Tang groups，and ketamine group，with 10 rats in each group．Except normal group，the depression model of rats was prepared by using chronic restraint stress（CRS）.The normal group and model group were intragastrically（ig） given normal saline．the modified Suanzaoren Tang groups were intragastrically given corresponding herbal drugs 6，12，24 g·kg-1， ketamine group group were given ketamine 0.015 g·kg-1 through intraoeritoneal injection，for 21 days，once a day．Then the depressive behaviors of rats were observed by Morris water maze and novelty feeding experiment.Western blot was used to detect the levels of DAR1，NMDAR2A，NMDAR2B，GluR1，mGluR1，CaMKⅡα and CaMKⅡβ protein expression in rat hippocampus tissue. Result:Compared with normal group，the time of novel ingestion and escape latencywere prolonged significantly（P<0.01）， and the time of space exploration was shortened significantly（P<0.01）.The levels of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ expression were increased significantly（P<0.01），while the levels of GluR1 and CaMKⅡα expression were decreased significantly（P<0.01）in model group. Compared with model group，the time of novel ingestion and escape latency were shortened significantly （P<0.01）， and the time of space exploration was prolonged significantly（P<0.01）.The levels of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ protein expression were decreased significantly（P<0.01），but the levels of GluR1 and CaMKⅡα expression were increased decreased significantly（P<0.01）in middle and high-dose modified Suanzaoren Tang groups. Conclusion:Modified Suanzaoren Tang can improve the behavior of chronic depression rats effectly. Its mechanism may be related with reduction the expression of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ protein ，increase the expression of GluR1and CaMKⅡα protein.

Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression / 中国实验方剂学杂志

Objective:To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases （PI3K）/protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/β-catenin signaling pathway of hippocampus in rats with depression. Method:A total of 120 SD rats were randomly divided into normal group，model group， and low， middle and high-dose Chaihu Jia Longgu Mulitang groups（3.25，6.5，13 g·kg-1）， and fluoxetine group， with 20 rats in each group. Except normal group， the depression model was prepared through chronic unpredictable mild stimulation（CUMS）. The normal group and the model group were given normal saline with 6.5 g·kg-1 by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75，6.5，13 g·kg-1， while fluoxetine group was intragastrically given fluoxetine 10 mg·kg-1 for 21 days， once a day. Then the depressive behaviors of rats were observed by sucrose preference test （SPT） and forced swimming test （FST）. Western blot was used to detect the protein expressions of PI3K，Akt，GSK3β and phosphorylation level. Result:Compared with normal group，the sucrose preference index was decreased significantly，while the immobility time in FST was increased significantly（P<0.01）， the protein expressions of PI3K， p-PI3K p110， p-PI3K p85 were decreased significantly （P<0.01）， and expressions of Akt， p-Akt Thr308，p-Akt Ser473， p-GSK3β Ser9 and β-catenin were decreased significantly（P<0.01）， while the level of GSK3β， p-GSK3β Tyr216 were increased significantly in model group（P<0.05，P<0.01）. Compared with model group，Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST（P<0.01）， the protein expressions of PI3K p110 and PI3K p85 was increased significantly （P<0.01）， levels of Akt Thr308，Akt Ser473， p-GSK3β Ser9， β-catenin were increased significantly （P<0.01）， whereas levels of GSK3β， and GSK3β Tyr216 were decreased significantly. Conclusion:Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus， activate Akt， inhibit GSK3β kinase activity and prevent β-catenin from degradation， so as to increase PI3K/Akt pathway activity in rat hippocampus， and protect hippocampal neurons.

Research Progress of ZHANG Zhong-jing's Classical Formulae in Treatment of Depression / 中国实验方剂学杂志

Depression is a kind of emotional and mental disorder， which is related to many pathogenic factors， such as abnormal metabolism of monoamine neurotransmitters， immune inflammatory reaction， neuroendocrine disorder and so on. it has the characteristics of high disability rate and high recurrence rate， which is seriously harmful to human health. It brings huge economic burden to patients and their families. At present， the commonly used antidepressants in clinic are monoamine oxidase inhibitors， tricyclic antidepressants and selective 5-hydroxytryptamine reuptake inhibitors. Long-term use causes adverse reactions such as cardiovascular， urinary and digestive dysfunction. The multi-target， multi-pathway and multi-mechanism of traditional Chinese medicine has played a great role in the treatment and rehabilitation of depression. At the same time， traditional Chinese medicine has gradually become a hot spot in the research and development of antidepressants because of its small side effects and good drug compliance. Especially the ZHANG Zhong-jing's classical formulae with precise medication and rigorous prescription has unique advantages in the treatment of depression. For thousands of years， it has been used clinically by countless doctors in the treatment of various types of depression， with definite curative effects and few side effects. In recent years， clinical research， experimental research， and pharmacological research around ZHANG Zhong-jing's classical formulae for depression have been continuously expanded and deepened. This article reveals the rules of medication of the treatment of depression with ZHANG Zhong-jing's classical formulae from three aspects of Bupleurum class prescription， Gardenia class prescription， and other prescriptions， which is reflected in the study on the composition of prescription， the etiology， and pathogenesis and the symptoms of the treatment. Integrating and classifying ZHANG Zhong-jing's classical formulae's experience in the treatment of depression， mainly expounded from two aspects， clinical research and pharmacological research， summarizing the research perspective and progress of Zhongjing prescription medicine in the treatment of depression in recent years， to excavate， inherit and develop ZHANG Zhong-jing's classical formulae， and provide experience and reference for the treatment of depression from multiple angles and ideas.

Expression Level and Clinical Significance of OTC4 Gene in Patients with Myelodysplastic Syndromes / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression characteristics and clinical value of OTC4 gene in patients with myelodysplastic syndrome (MDS).@*METHODS@#Sixty-five patients with MDS were selected from June 2017 to April 2018, and 39 healthy subjects were selected as control group. Mononuclear cells were isolated from bone marrow collected by aseptic puncture. The OTC4 gene level of MDS patients was detected by RT-PCR, and the OTC4 protein of MDS patients was detected by Western blot. The survival curve of MDS patients was drawn by Kaplan-Meier. Cox multivariate analysis was used to analyze the independent prognostic factors.@*RESULTS@#The relative expression level of OTC4 gene in MDS patients was significantly higher than that in the control group (P＜0.05). Western blot showed that the expression level of OTC4 protein in MDS patients was higher than that in the control group (P＜0.05). OTC4 gene expression level closely related with the leukocyte count, and the level of hemoglobin, and lactate dehydrogenase and platelet count in MDS patients (P＜0.05). CR rate of MDS patients with low OTC4 gene expression was 54.8%, which was higher than that of high OTC4 gene expression group (P＜0.05), while HI, SD and PD rates of MDS patients with low OTC4 gene expression were 9.7%, 12.9% and 6.5% respectively, which were lower than those of high OTC4 gene expression group (P＜0.05). Kaplan-Meier survival analysis showed that OS and DFS in patients with low OTC4 gene expression were superior to those with high OTC4 gene expression (P＜0.05). Multivariate Cox regression analysis showed that leukocyte count and OTC4 gene were independent influencing factors for OS (P＜0.05), platelet level and OTC4 gene expression were independent influencing factors for DFS (P＜0.05).@*CONCLUSION@#OTC4 gene closely relates with the severity of MDS. The patients with lower expression of OTC4 gene have better prognosis, the detection of OTC4 gene has higher clinical value for evaluating the prognosis of MDS patients.

Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB (NF-κB) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD). Method: Forty SD rats were randomly divided into normal group, model group, modified Erchentang group and EVP4593 (NF-κB inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling, normal and model groups were intragastrically given normal saline solution, EVP4593 group was given EVP4593(1 mg · kg-1) through subcutaneous injection, and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g · kg-1) for 14 days. The levels of high mobility group box 1(HMGB1), chemokines CXCL-2, CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB p65 (NF-κB p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4, MyD88, NF-κB p65 and p-NF-κB p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4, MyD88 and p-NF-κB p65 protein in the lung tissue. Result: The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 were increased significantly (PPκB p65 mRNA and protein were decreased significantly (PConclusion: Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-κB pathway and the reduction of the release of HMGB1, CXCL-2, CXCL-3 and MCP-1.

Effect of Modified Erchentang on NLRP3 Inflammasome Expression in Peripheral Blood Mononuclear Cells (PBMCs) of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To observe the effect of modified Erchentang on the expressions of NLRP3 inflammasome genes in peripheral blood mononuclear cells (PBMCs) and the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)and chemokine8 (CXCL8) in lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the molecular mechanism of modified Erchentang against inflammation of COPD. Method: Forty SD rats were randomly divided into normal control group, model group, MCC950 (NLRP3 inhibitor) group and modified Erchentang group. The COPD model of rats was prepared by using cigarette smoke and dripping with lipopolysaccharide (LPS). During the modeling period (from the 1st to the 30th day), the MCC950 group received a single intraperitoneal injection with 60 mg · kg-1 on the first day of the experiment,and the modified Erchentang group was given intragastric administration with 10 g · kg-1, once every 2 days. From the 31st to the 45th day, the MCC950 group was intraperitoneally injected with 3 mg · kg-1, once every 2 days, the modified Erchentang group was given intragastric administration with 10 g · kg-1, twice a day, and the normal group and the model group received normal saline (NS) with 10 g · kg-1, twice a day. The levels of interleukin-1β(IL-1β), interleukin-18(IL-18) and chemokine8 (CXCL8) in rats lung tissue homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteinyl aspartate specific proteinase-1 (Caspase-1) mRNA in PBMCs were measured by Real-time fluorescence quantitative PCR (Real-time PCR). Western blot was used to detect the levels of NLRP3, ASC and Caspase-1 proteins in PBMCs. Immunohistochemical(IHC)method was used to detect the expressions of NLRP3, ASC and Caspase-1 proteins in lung tissues. Result: The expressions of NLRP3, ASC and Caspase-1 mRNA and protein were increased significantly (PPPβ and CXCL8 in lung tissue homogenate in model group were significantly higher than those in the control group. However, compared with model group, the levels of IL-18, IL-1β and CXCL8 were decreased significantly (PPConclusion: NLRP3 inflammasome is involved in the inflammatory response in COPD rats. Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be correlated with the reduction of NLRP3, ASC and Caspase-1 gene expressions, and the inhibition of the release of IL-18, IL-1β and CXCL8.

Effect of Modified Erchentang on VEGF,VEGFR2,IL-4,ET-1 in Chronic Obstructive Pulmonary Disease Rats / 中国实验方剂学杂志

Objective: To observe the effects of Erchen on vascular endothelial growth factor (VEGF) and its receptor R2 (VEGFR2), interleukin (IL)-4 and endothelin-1 (ET-1) in rats with chronic obstructive pulmonary disease (COPD). Method: The 50 SD rats were randomly divided into 5 groups, 10 rats in each group, which were normal group, model group, Erchentang low, medium and high dose group (10, 20, 40 g · kg-1 · d-1). COPD rat model was established by smoking combined with lipopolysaccharide (LPS) intratracheal drip. After successful modeling, the treatment group was given intragastric administration, and the normal group and the model group were given intragastric distilled water of equal volume. The pathological changes of pulmonary vessels in rats were observed by light microscopy, and the thickness of pulmonary vascular wall was measured. The concentration of IL-4 in rat serum, bronchoalveolar lavage fluid (BALF) and lung homogenate was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of ET-1 and immunohistochemistry was used to detect the expression of VEGF,VEGFR2 and ET-1 in lung tissue. Result: Compared with normal group, the concentration of IL-4 in serum, BALF and lung homogenate of model group rats decreased significantly (PPPPPPConclusion: Modified Erchentang can alleviate the process of pulmonary inflammation and pulmonary vascular remodeling in COPD rats, and slow down the progress of COPD and its complications by increasing the content of IL-4, inhibiting the expression of VEGF, VEGFR2, ET-1.

Effect of Modified Erchentang on Expression of IL-19,IL-20R1,IL-20R2 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To observe the effect of modified Erchentang on the expression of interleukin-19 (IL-19), interleukin-20 (IL-20)and their receptor IL-20R1, IL-20R2 in bronchioles of rats with chronic obstructive pulmonary disease (COPD), and to explore the molecular mechanism of modified Erchentang on anti-inflammatory of COPD. Method: The model of rat with COPD was established by cigarette smoke combined with lipopolysaccharide (LPS). The experimental rats were randomly divided into 6 groups:normal group, model group, modified Erchentang high, medium and low dose group, and Jizhitangjiang group. Normal group and model group fed with normal saline 4 mL · d-1, modified Erchentang high, middle, low dosage group(20,10,5 g · kg-1 · d-1).The dosage of Jizhitangjiang group was 12 g · kg-1 · d-1, all groups were given intragastric administration for 14 days, twice a day. To observe the general situation of rats.To evaluate the pulmonary function of rats. To detect the contents of IL-10, IL-19 and IL-20 in serum by enzyme-linked immunosorbent assay (ELISA).To observe the pathological changes of bronchiole tissue by light microscopy.To detect the expression of IL-20R1 and IL-20R2 in bronchiole tissue by immunohistochemistry. Result: Compared with normal group, peak expiratory flow(PEF), forced expiratory volume in one second(FEV1), forced vital capacity (FVC), and FEV1/FVC in model group were significantly increased (PPP1 and in bronchioles tissue significantly increased (P1, FVC, FEV1/FVC of Jizhitangjiang group, modified Erchentang high, medium and low dosage group were significantly increased(PPP1 and IL-20R2 in bronchioles tissue was significantly decreased (PConclusion: Modified Erchentang can improve the lung function and protect the tissue structure of bronchioles in COPD rats, which may be related to the inhibition of the expression of IL-19, IL-20 and their receptor IL-20R1, IL-20R2 in bronchioles of rats with modified Erchentang.