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Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.
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ObjectiveTo explore the mechanism of the combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） in alleviating pulmonary edema in rats with acute lung injury （ALI） induced by lipopolysaccharide （LPS）. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine， and positive control group. LPS （10 mg·kg-1） was given （ip） to induce ALI in rats. After modeling， the blank group was given normal saline （25 mL·kg-1）， the combined therapy of lung and intestine treatment groups were given （ig） low- （5 g·kg-1）， medium- （7.5 g·kg-1）， and high-dose （10 g·kg-1） Mahuangtang and Da Chengqitang， and the positive control group was given dexamethasone （5 mg·kg-1）. Medications were administered 0， 8， and 16 h after LPS injection for 3 times. Then lung tissue and serum were collected after administration. The lung tissues were stained with haematoxylin-eosin （HE）， and the pulmonary edema score was evaluated. The dry/wet （D/W） weight ratio of lung tissues in each group was measured， and the content of serum vasoactive intestinal peptide （VIP） in rats was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of aquaporin-1 （AQP1）， AQP5， VIP， cyclic adenosine monophosphate （cAMP）， phosphorylated protein kinase A （p-PKA）， and PKA in lung tissues of rats in each group. The level of VIP mRNA in lung tissues of rats was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group exhibited obvious lung injury， increased edema score， decreased D/W ratio （P<0.01）， declined AQP1， AQP5， cAMP， and p-PKA/PKA in lung tissues （P<0.05， P<0.01）， elevated VIP content （P<0.01）， and up-regulated levels of VIP protein and mRNA in lung tissues （P<0.05， P<0.01）. Compared with the model group， combined therapy of lung and intestine treatment groups showed alleviated lung injury， increased D/W ratio （P<0.01）， elevated AQP1， AQP5， VIP， cAMP， and p-PKA/PKA in lung tissues （P<0.05， P<0.01）， and up-regulated VIP levels in lung tissues （P<0.05， P<0.01）. ConclusionThe combined therapy of lung and intestine can alleviate ALI-induced lung tissue edema， and the mechanism may be related to the activation of the VIP/cAMP/PKA signaling pathway， which further promotes the expression of AQP1 and AQP5 and enhances the water metabolism of lung tissue.
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ObjectiveTo investigate the effect of combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in rats and its protective mechanism. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine ， and dexamethasone group. LPS （10 mg·kg-1） was given （ip） to induce ALI in rats. The general state of rats in each group was observed and recorded. The body temperature of rats in each group was recorded 0-8 h after modeling by means of anal temperature measurement. Serum and lung tissues were collected 24 h after modeling. Serum levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and arginase-1 （Arg-1） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of nuclear factor kappa B p65 （NF-κB p65）， phosphorylated NF-κB p65 （p-NF-κB p65）， NF-κB inhibitor α （IκBα）， and phosphorylated IκBα （p-IκBα） in lung tissues of rats. The levels of classically activated （M1） macrophage marker CD80 and IL-1β and macrophage markers F4/80 and IL-10 were detected by double immunofluorescence. ResultCompared with the blank group， the model group showed increased body temperature and thermal response index （TRI）， elevated serum levels of pro-inflammatory factor TNF-α and IL-1β and anti-inflammatory factor IL-10 （P<0.01）， up-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.01）， and increased levels of F4/80， CD80， and IL-1β in lung tissues （P<0.01）. Compared with the model group， the lung-intestine combined treatment groups and the dexamethasone group exhibited decreased body temperature and TRI in rats （P<0.01）， declined serum levels of inflammatory factor TNF-α and IL-1β （P<0.05， P<0.01）， elevated serum levels of anti-inflammatory factor IL-10 and Arg-1 （P<0.05， P<0.01）， down-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.05， P<0.01）， decreased levels of CD80 and IL-1β， and increased levels of IL-10 in lung tissues （P<0.01）， while the level of F4/80 was not significantly changed. ConclusionThe combined therapy of lung and intestine can obviously alleviate the fever and inflammatory state of ALI rats， and the mechanism may be related to the inhibition of NF-κB inflammatory pathway and the polarization of lung tissue macrophages to anti-inflammatory phenotype.
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Stroke is a destructive cerebrovascular event caused by the interruption of cerebral blood flow caused by the blockage or rupture of cerebral vessels， which is easy to cause physical disability and multiple functional injuries. The mortality rate of stroke patients in China occupies the first place in the world. How to effectively treat stroke is one of the urgent health problems to be solved. In the clinic， academician WANG Yong-yan observed that 60% of stroke patients with heat-phlegm and sthenic-Fu syndrome. Most of the patients with heat-phlegm and sthenic-Fu syndrome are characterized by stagnation of stool， bad breath and dry pharynx， and so on， After clinical practice， Xinglou Chengqi decoction （XLCQD） was established to treat stroke patients with heat-phlegm and sthenic-Fu syndrome. XLCQD is one of the representative prescriptions for removing phlegm to relax bowels， which is composed of Rhei Radix et Rhizoma， Natrii Sulfas， Trichosanthis Fructus and Arisaema Cum Bile by the ratio of 5∶5∶15∶3. At present， the research on XLCQD is mainly focused on clinical observation and pharmacological mechanism， while the basic research of its pharmacodynamic substance is relatively weak. This paper intends to sort out the chemical composition and pharmacological mechanism of XLCQD， in order to provide the basis for the chemical component identification， drug target prediction and material basis screening of this compound in the later stage. In addition， through the case analysis of XLCQD and modified XLCQD in the treatment of stroke， its rules of clinical application were summarized， in order to provide reference for the clinical application of this compound.
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Objective:To explore the efficacy and mechanism of modified Da Chengqitang in treating hyperlipidemic acute pancreatitis （HLAP） with damp heat accumulation syndrome. Method:A total of 110 patients with HLAP with damp heat accumulation syndrome treated at our hospital were randomly divided into control group and observation group， with 55 cases in each group， both groups were treated with low molecular weight heparin calcium， insulin and alprostadil injection. Control group was given Huazhironggan granules in addition to the basic therapy， while observation group was given modified Da Chengqitang in addition to the basic therapy. After 7 days， the clinical efficacy， traditional Chinese medicine (TCM） syndrome score， gastrointestinal function recovery， acute pancreatitis bedside index （BISAP）， acute physiology and chronic health status Ⅱ （APACHE Ⅱ）， inflammatory factors， such as tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6） and C-reactive protein （CRP）， oxidative stress， such as malondialdehyde （MDA）， oxidized glutathione （GSSG）， total antioxidant capacity （T-AOC）， total cholesterol （TC）， triglyceride （TG）， high and low density lipoprotein （HDL-C， LDL-C） blood lipid indicators and safety were evaluated. Result:The clinical efficacy of observation group was significantly better than that of control group （<italic>Z</italic>=3.353， <italic>P</italic><0.05）， and the total effective rate of observation group was 94.55%， which was higher than 74.55% of control group （<italic>χ<sup>2</sup></italic>=8.419， <italic>P</italic><0.01）. After treatment， the scores of abdominal pain， stool obstruction， chest tightness and fever in observation group were significantly lower than those of control group （<italic>P</italic><0.05）. The gastric tube indwelling exhaust time， defecation time and recovery time of bowel sounds in observation group were significantly lower than those of control group （<italic>P</italic><0.05）. The scores of BISAP and APACHE Ⅱ in two groups were significantly decreased， and the BISAP and APACHE Ⅱ scores of observation group were lower than control group （<italic>P</italic><0.05）. After treatment， the serum levels of TNF-<italic>α</italic>， IL-6 and CRP in observation group were significantly lower than those in control group. The levels of serum MDA， GSSG in two groups were significantly decreased， whereas the T-AOC level was significantly increased； and the level of serum MDA， GSSG observation group was lower than control group， while the T-AOC level was higher than control group （<italic>P</italic><0.05）. After treatment， the levels of TC， TG and LDL-C in two groups were decreased， while the level of HDL-C was increased， the levels of TC， TG and LDL-C in observation group were lower than those in control group， and the HDL-C was higher than that control group （<italic>P</italic><0.05）. Conclusion:modified Da Chengqitang has a definite clinical efficady in treating HLAP with damp heat accumulation syndrome， and can alleviate TCM syndrome and patient symptoms， reduce inflammatory factors， inhibit oxidative stress of the body. It has a good safety， and is worthy of clinical application.
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Objective: To observe the efficacy of umbilical moist-heat application of modified Da Chengqitang in treating ventosity after noninvasive ventilation, and the regulatory effect on level of gastrointestinal motility hormone. Method: One hundred and sixty patients were randomly divided into control group and observation group by random number table. Patients in control group got mosapride citrate tablets, 5 mg/time, 3 times/days. In addition tothe therapy in control group, patients in observation group was also given mbilical moist-heat application of modified Da Chengqitang, 30 min/time, 2 times/day. And a course of treatment was 7 days. Before and after treatment, degree of abdominal distention was measured by a tape and subjective evaluation. Time of recovery of bowel sounds, remission of abdominal distention, exhausting and defecation, and the total time of using respirator, pressure of using respirator, and the total days of using respirator were recorded. And levels of gastrin (GAS), motilin (MTL), vasoactive intestinal peptide (VIP) and somatostatin (SS) were detected. Result: According to the rank sum test, the clinical effect in observation group was superior to that in control group (Z=2.484, PZ=2.456, PPPPP2, PaCO2, GAS, MTL were higher than those in control group, whereas PaCO2, VIP and SS were lower than those in control group (PPConclusion: Umbilical moist-heat application of modified Da Chengqitang can relieve abdominal distention and dyspnea, reduce intraperitoneal pressure, improve the recovery of gastrointestinal function, and regulate gastrointestinal hormone level.
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Acute pancreatitis (AP) is a common clinical acute abdominal disease, which can be divided into three types:mild, moderate and severe. Severe acute pancreatitis still has a high mortality rate, but there is no specific drug for this disease, and non-operative symptomatic supportive treatment is the main therapy in the early stage of the disease. In recent years, a large number of clinical studies have shown that traditional Chinese medicine has a unique advantage in prevention and treatment of AP. According to the characteristics of the disease, such as abdominal pain, no stool, treatment based on syndrome differentiation can alleviate a series of symptoms, especially the formulations of "removing stasis by purgation" represented by Da Chengqitang, including the formula evolved based on Da Chengqitang. Specifically, Chaishao Chengqitang and Chaiqin Chengqitang can improve intestinal function, alleviate gastrointestinal symptoms, such as intestinal paralysis combined with AP patients, prevent intestinal flora ectopia, protect intestinal mucosal barrier function, and help activate enteral nutrition in early stage, regulate immune inflammatory response, so as to avoid systemic inflammatory response syndrome. In addition, categorized formulas Da Chengqitang can also promote pancreatic microcirculation, promote the recovery of damaged parts of pancreas during AP pathogenesis, reduce blood amylase, and improve systemic coagulation function and treatment effect. In China, integrated traditional Chinese and Western medicine treatment has become an important part of the treatment of AP at present. It can prevent AP from aggravating, reduce complications and shorten hospitalization time. To summarize the therapeutic effect of Da Chengqitang and its categorized formulas on AP in clinic, the authors review clinical studies of categorized formulas Da Chengqitang on AP in recent five years based on "intestinal function, intestinal nutrition, inflammatory mediators and pancreatic microcirculation".
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Objective: To explore the effect of Da Chengqitang on the lung index,lung index inhibition rate,lung histological morphology,classification changes of inflammatory cells and mitogen-activated protein kinase (MAPK) signal pathway in mice with allergic asthma.Method: Forty female C57BL/6 mice were randomly divided into normal control group,model group,dexamethasone group (0.005 g·kg-1) and Da Chengqitang group (19 g·kg-1).Murine allergic asthma model was established by sensitization and nebulization of ovalbumin (OVA).In brief,asthmatic mice were first sensitized by OVA and Al (OH)3 mixture ip on day 0 and day 14,and then nebulized by OVA from day 21 to 27.At the same time,each mouse in the dexamethasone and Da Chengqitang groups were intragastrically administered with 0.2 mL corresponding medicine one hour before the nebulization challenge,while the normal control group was given with the same amount of normal saline.On day 28,pulmonary morphology was detected by htoxylin eosin (HE) staining and inflammatory cells from the brachial alveolar lavage fluid were counted by Diff staining.The expression levels of key proteins in MAPK signaling pathway were detected by Western blot.Result: As compared with the normal control group,the lung indexes were significantly increased in model group (PP0.01),with a predominant percentage of eosinophils,moreover,the expression levels of phosphorylated p38 MAPK and extracellular signal-regulated kinase 1/2(ERK1/2) were increased obviously in asthmatic mice.After treatment by Da Chengqitang,lung indexes and pulmonary inflammation were significantly decreased,with an inhibitory rate of 68.4% for lung indexes,and inflammatory pathology of lung tissues was obviously improved and inflammatory cell exudation was alleviated,with the obviously lower levels of phosphorylated p38 MAPK and ERK1/2 protein.Conclusion: Da Chengqitang based on "Pulmonary Intestinal Treatment" can effectively improve lung inflammation in mice with allergic asthma,which may be related to the expression of phosphorylated p38 MAPK and ERK1/2 protein.
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Objective: To discuss the clinical efficacy of modified Da Chengqitang by enema in treatment of postoperative inflammatory intestinal obstruction (EPISBO) after the operation and its effect on inflammatory factors, gastrointestinal motility and intestinal barrier function. Method: One hundred and six patients were randomly divided into control group (52 cases) and observation group (54 cases) by random number table. Patients in both groups were given fasting for solids and liquids, gastrointestinal decompression, maintaining water and electrolyte balance, nutritional support and other basic therapies. Patients in control group were given somatostatin for injection for continuous micro-pumping, 0.003 5 mg·h-1·kg-1, dexamethasone acetate tablets, 2.5-5 mg/time, 2 time/days. Patients with concurrent infection got ceftazidime for injection, 30-100 mg·kg-1, 2-3 intravenous drips. In addition to the therapy of control group, patients in observation group were also given modified Da Chengqitang, 125 mL/time, 2 times/days. A course of treatment was 5 days. Time of remission of abdominal distention, recovery of exhaust gas, bowel sounds and diet, defecation, hospitalization and transitional surgery were recorded. And main gastrointestinal symptoms and signs were scored. And levels of serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), vasoactive intestinal peptide (VIP), gastrin, motilin, diamine oxidase and D lactic acid were detected. Result: After treatment, according to rank sum test analysis, the clinical efficacy in observation group was better than that in control group (PPPPα, hs-CRP, VIP, DAO, D-lactic acid and scores of main gastrointestinal symptoms and signs were all lower than those in control group (PPConclusion: In addition of routine therapy of western medicine, modified Dachengqi Tang had effects in resisting inflammation, regulating gastrointestinal hormones, and protecting intestinal barrier function, so can improve gastrointestinal motility, alleviate symptoms, shorten the course of disease and improve the clinical efficacy.