Interaction pathways of implant metal localized corrosion and macrophage inflammatory reactions

Macrophages play a central role in immunological responses to metallic species associated with the localized corrosion of metallic implants,and mediating in peri-implant inflammations.Herein,the pathways of localized corrosion-macrophage interactions were systematically investigated on 316L stainless steel(SS)implant metals.Electrochemical monitoring under macrophage-mediated inflammatory conditions showed a decreased pitting corrosion resistance of 316L SSs in the presence of RAW264.7 cells as the cells would disrupt biomolecule adsorbed layer on the metal surface.The pitting potentials were furtherly decreased when the RAW264.7 cells were induced to the M1 pro-inflammatory phenotype by the addition of lipopolysaccharide(LPS),and pitting corrosion preferentially initiated at the peripheries of macrophages.The overproduction of aggressive ROS under inflammatory conditions would accelerate the localized corrosion of 316L SS around macrophages.Under pitting corrosion condition,the viability and pro-inflammatory polarization of RAW264.7 cells were region-dependent,lower viability and more remarkable morphology transformation of macrophages in the pitting corrosion region than the pitting-free region.The pitting corrosion of 316L SS induced high expression of CD86,TNF-α,IL-6 and high level of intracellular ROS in macrophages.Uneven release of metallic species(Fe^(2+),Cr^(3+),Ni^(2+),etc)and uneven distribution of surface overpotential stimulated macrophage inflammatory responses near the corrosion pits.A synergetic effect of localized corrosion and macrophages was revealed,which could furtherly promote localized corrosion of 316L SS and macrophage inflammatory reactions.Our results provided direct evidence of corrosion-macrophage interaction in metallic implants and disclosed the pathways of this mutual stimulation effect.

Effect of Shengmai Injection(生脉注射液) on Cardiac Function and Inflammatory Reaction in Patients with Acute Coronary Syndrome

Objective： To confirm the effect of Shengmai Injection （生脉注射液, SMI） in improving cardiac function in patients with acute coronary syndrome （ACS） and to explore its influence on inflammatory reaction in patients. Methods： Ninety ACS patients were randomized into two groups, the control group treated with conventional therapy and the SMI group treated with SMI. The patients＇ cardiac function was noted and the content of high sensitive C-reactive protein （hs-CRP） in venous blood was measured before treatment and 1 week and 3 weeks after treatment, so as to observe and compare their changes between the two groups. Results： The cardiac output, stroke volume and ejection fraction in the SMI group after 3 weeks of treatment were all higher than those in the control group （P〈0.05）. The serum content of hs-CRP was reduced in both groups （P〈0.05）, but the reduction in the SMI group was more significant than that in the control group （P〈0.05）. Conclusion： SMI could improve the cardiac function and further inhibit the inflammatory reaction in patients with ACS.

Effect of Chinese Drugs for Activating Blood Circulation and Detoxifying on Indices of Thrombosis,Inflammatory Reaction,and Tissue Damage in A Rabbit Model of Toxin-Heat and Blood Stasis Syndrome

Objective： To observe the regulatory effect of Chinese drugs for activating blood circulation （ABC） and for activating blood circulation and detoxifying （ABCD） on indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model of toxin-heat and blood stasis syndrome. Methods： Fifty-four rabbits were randomized into the normal control group, model group, simvastatin group （simvastatin, 0.93 mg/kg per day）, ABC group [Xiongshao Capsule （~ff_）, 0.07 g/kg per day], and ABCD group [Xiongshao Capsule, 0.07 g/kg per day, and Huanglian Capsule （-~L^t）, 0.14 g/kg per day]. All except the normal control group received a single injection of bovine serum albumin and were fed with high-fat diets for 6 weeks. At the end of week 4 of giving high- fat diets, a dose of endoxitin was given by ear vein injection, and a randomized 2-week treatment was initiated. At the end of treatment, blood lipids, circulating endothelial cells, and the pathological changes of the aortic arch were assessed. The serum levels of matrix metalloproteinases （MMP-9）, tissue inhibitors to metalloproteinase （TIMP-1）, granule membrane protein-140 （GMP-140）, plasminogen activator inhibitor-1 （PAl-l）, high-sensitivity C-reactive protein （hs-CRP）, interleukin-6 （IL-6）, and tumor necrosis factor- ~ （TNF- oL ） were determined. Results： Compared with the model group, ABCD group showed decreased serum triglycaride （TG） level, improvement in the pathological change in the aortic arch, and reduction in the number of circulating endothelial cells （4.00_＋ 1.41 per 0.9 p~ L for ABCD group vs 7.83_＋ 1.72 per 0.9 μL for the model group）. In addition, the levels of serum GMP-140, PAl-l, and IL-6 in ABCD group were also significantly reduced [0.79＋0.20 ng/mL, 5.23± 1.39 ng/mL, 40.64 ± 10.11 pg/mL for ABCD group vs 1.08 ± 0.31 ng/mL, 7.28± 2.01 ng/mL, 54.44 ± 13.56 pg/mL for the model group, respectively, P〈0.05]. A trend showing improvement in the indices of thrombosis, inflammatory reaction, and tissue damage was observed in the ABC group when compared to the model group, but the changes were not statistically significant （P〉0.05）. Conclusions： Chinese drugs for activating blood circulation and detoxifying have beneficial effects on regulating indices of thrombosis （GMP-140 and PAl-l） and inflammatory reaction （IL-6） in rabbit model with toxic-heat and blood stasis. The effect of the activating blood circulation and detoxifying drugs in regulating the levels of serum GMP-140, PAl-l, and IL-6 was superior to that of the activating blood circulation drugs.

Effect of Chinese Herbal Medicine for Activating Blood Circulation and Detoxifying on Expression of Inflammatory Reaction and Tissue Damage Related Factors in Experimental Carotid Artery Thrombosis Rats

Objective：To observe the pharmaceutical effect of Chinese drugs for activating blood circulation （Xiongshao Capsule,XSC,芎芍胶囊）and for activating blood circulation and detoxification（Xiongshao Capsule and Huanglian Capsule,XSHLC,黄连胶囊）in terms of the indices of thrombosis,inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.Methods：Fifty Wistar rats were randomly divided into the sham operation group,the model group,the Simvastatin group（SG）,the activating blood circulation（ABC）group,and the activating blood circulation and detoxifying（ABCD）group,with 10 rats in each group.Simvastatin（1.8 mg/kg）,XSC（0.135 g/kg）and XSHLC（0.135 g/kg）were administered to Simvastatin,ABC and ABCD group by gastrogavage,and an equal volume of normal saline was given to the sham operation group and the model group.After 2 weeks of successive medication,the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model.The serum levels of matrix metalloproteinases（MMP-9）,tissue inhibitors to metalloproteinase（TIMP-1）,granule membrane protein-140（GMP-140）,tissue-type plasminogen activator（t-PA）,high-sensitivity C-reactive protein（hs-CRP） and interleukin-6（IL-6）were detected with enzyme-linked immunoassay 24 h later.Results：Compared with the model group,the levels of serum GMP-140,hs-CRP,IL-6 and MMP-9 were significantly decreased,and the level of t-PA was significantly increased in the ABC and ABCD group（P〈0.05）,while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group（P〈0.05）.Conclusions：Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis,inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats.The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching

BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.

Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.

Inflammatory response and neuronal necrosis in rats with cerebral ischemia

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap- peared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia,

Role of inflammatory cytokines in peripheral nerve injury

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.

Delayed xenon post-conditioning mitigates spinal cord ischemia/reperfusion injury in rabbits by regulating microglial activation and inflammatory factors

The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury. To investigate how xenon regulates microglial activation and the release of inflammatory factors, a rabbit model of spinal cord ischemia/reperfusion injury was induced by balloon occlusion of the infrarenal aorta. After establishment of the model, two interventions were given： （1） immediate xenon post-conditioning—after reperfusion, inhalation of 50% xenon for 1 hour, 50% N2/50%O2 for 2 hours; （2） delayed xenon post-conditioning—after reperfusion, inhalation of 50% N2/50%O2 for 2 hours, 50% xenon for 1 hour. At 4, 8, 24, 48 and 72 hours after reperfusion, hindlimb locomotor function was scored using the Jacobs locomotor scale. At 72 hours after reperfusion, interleukin 6 and interleukin 10 levels in the spinal cord of each group were measured using western blot assays. Iba1 levels were determined using immunohistochemistry and a western blot assay. The number of normal neurons at the injury site was quantified using hematoxylin-eosin staining. At 72 hours after reperfusion, delayed xenon post-conditioning remarkably enhanced hindlimb motor function, increased the number of normal neurons at the injury site, decreased Iba1 levels, and inhibited interleukin-6 and interleukin-10 levels in the spinal cord.Immediate xenon post-conditioning did not noticeably affect the above-mentioned indexes. These findings indicate that delayed xenon post-conditioning after spinal cord injury improves the recovery of neurological function by reducing microglial activation and the release of interleukin-6 and interleukin-10.

Different positive end expiratory pressure and tidal volume controls on lung protection and inflammatory factors during surgical anesthesia

BACKGROUND Mechanical ventilation can lead to the severe impairment of the metabolic pathway of alveolar surfactants,inactivating alveolar surfactants and significantly reducing lung-chest compliance.The cardiopulmonary function of elderly patients usually reduced to a certain extent,and there are lung complications after surgical anesthesia,just like lung barotrauma caused by mechanical ventilation,atelectasis and postoperative hypoxemia.AIM To investigate the effects of different positive end expiratory pressures(PEEPs)and tidal volumes(VTs)on respiratory function,the degree of the inflammatory response and hemodynamic indexes in patients undergoing surgery under general anesthesia.METHODS A total of 120 patients undergoing surgery for gastric or colon cancer under general anesthesia in Xinghua People's Hospital from January 2017 to January 2021 were randomly divided into Group A and Group B,with 60 cases in each group.The ventilation mode in Group A was VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O),while that in Group B was VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O).Blood gas parameters,respiratory mechanical parameters,inflammatory response indicators,hemodynamic indicators and related complications were compared between the two groups.RESULTS There were no significant differences in PaCO_(2),PaO_(2),oxygen or the examined indexes at T0 between group A and group B(P>0.05).The measured PaO_(2) value of patients in group A at T3 was higher than that in group B,and the difference was significant(P<0.05).There were no significant differences in peak airway pressure(P_(peak)),mean airway pressure or dynamic pulmonary compliance(Cdyn)at T0 between group A and group B(P>0.05).The measured P_(peak) value of patients in group A at T1 was higher than that in group B,and the difference was significant(P<0.05).The measured Cdyn value at T1 and T2 was greater than that in group B(P<0.05).Before surgery,there were no significant differences in tumor necrosis factor-α(TNF-α),interleukin(IL)-6 or IL-10 between group A and group B(P>0.05).After 4 h,the measured values of TNF-αand IL-6 in group A were lower than those in group B,and the differences were significant(P<0.05).The IL-10 Level in group A was higher than that in group B(P<0.05).At T0,there were no significant differences in cardiac output,cardiac index(CI),stroke volume index(SVI)or mean arterial pressure between group A and group B(P>0.05).The measured values of CI and SVI at T2 in patients in group A were higher than those in group B,and the differences were significant(P<0.05).CONCLUSION For patients undergoing surgery for gastric or colon cancer under general anesthesia,the VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O)regimen was more effective than the VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O)regimen in protecting the lung function and ventilatory function of patients,and it had better effects on maintaining hemodynamic stability and reducing inflammatory reactions.

Delayed inflammatory response evoked in nasal alloplastic implants after COVID-19 vaccination: A case report

BACKGROUND Delayed inflammatory reactions(DIRs)in alloplast rhinoplasty are a rare complication that may occur several months to years after surgery.The exact causes and mechanisms are unclear,but several triggering factors,including infections,trauma,dental procedures,and vaccination,have been reported.CASE SUMMARY A 39-year-old male patient who had undergone augmentation rhinoplasty 8 years ago had DIRs after the administration of the first dose of the mRNA Pfizer coronavirus disease 2019(COVID-19)vaccine.He suddenly had tender,erythematous swelling on his face 6 d after vaccination.As there was no improvement in the patient’s condition after the conservative treatment,surgical removal of an alloplastic nasal implant was performed.Immediately after the surgery,the DIRs and accompanying symptoms ameliorated rapidly.A histological study conducted during surgery was fibrosis and small fragments of the hyaline cartilage.CONCLUSION The correlation between DIRs and COVID-19 vaccination has not been reported yet and the exact mechanism is unclear.Because the uncontrolled inflammatory reactions on the nose leave serious sequelae,surgeons should be conscious of the correlation between COVID-19 vaccines and DIRs associated with nasal alloplastic implants.And further histological or microbiological studies should be performed to determine the cause of DIRs.

Obesity is positively Associated with Depression in Older Adults:Role of Systemic Inflammation

Objective We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults.Methods Adults≥65 years old(n=1,973)were interviewed at baseline in 2018 and 1,459 were followed up in 2021.General and abdominal obesity were assessed,and serum C-reactive protein(CRP)levels were measured at baseline.Depression status was assessed at baseline and at follow-up.Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms,as well as the relationship between obesity and CRP levels.The associations of CRP levels with the geriatric depression scale,as well as with its three dimensions,were investigated using multiple linear regressions.Results General obesity was associated with worsening depression symptoms and incident depression,with an odds ratio(OR)[95%confidence interval(CI)]of 1.53(1.13-2.12)and 1.80(1.23-2.63),especially among old male subjects,with OR(95%CI)of 2.12(1.25-3.58)and 2.24(1.22-4.11),respectively;however,no significant relationship was observed between abdominal obesity and depression.In addition,general obesity was associated with high levels of CRP,with OR(95%CI)of 2.58(1.75-3.81),especially in subjects free of depression at baseline,with OR(95%CI)of 3.15(1.97-5.04),and CRP levels were positively correlated with a score of specific dimension(life satisfaction)of depression,P<0.05.Conclusion General obesity,rather than abdominal obesity,was associated with worsening depressive symptoms and incident depression,which can be partly explained by the systemic inflammatory response,and the impact of obesity on depression should be taken more seriously in the older male population.

A study on the mechanism of acupuncture treatment of acne based on immune inflammation

Acne is a chronic inflammatory skin disease involving hair follicle sebaceous glands,which is characterized by acne,papules,pustules,nodules,cysts and so on.The disorder of immune inflammation is the key link.A variety of factors participate in the immune inflammatory response of acne and interact with each other,leading to the occurrence and development of acne inflammation.Acupuncture can regulate the immune and inflammatory response through many links and improve the skin lesions.This study explains potential mechanisms of acupuncture in the treatment of acne by regulating the body's immune inflammatory response,in order to provide new ideas.

Effect of tumor necrosis factor-alpha in rats with hepatic ischemia-reperfusion injury

BACKGROUND: With the development of hepatic surgery, especially liver transplantation, the pathophysiological processes of hepatic ischemia-reperfusion (I/R) injury have gained special attention. Controlling I/R injury has become one of the most important factors for successful liver transplantation. This study aimed to investigate the effects of tumor necrosis factor-alpha (TNF-alpha) in rats with hepatic I/R injury and promote the recognition of I/R injury in the liver. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into 2 groups. Rats in the sham-operated (SO) group served as controls. Rats in the hepatic ischemia-reperfusion (I/R) group underwent reperfusion after 30 minutes of liver ischemia. Rats were sacrificed at 1, 6 and 12 hours. The expression of TNF-alpha mRNA in the liver was measured by RT-PCR. Histological changes in the liver were assessed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured. RESULTS: The expression of TNF-alpha mRNA in the SO group was decreased compared with that in the I/R group (P<0.05). TNF-a mRNA expression progressively increased in the I/R group. The serum levels of ALT and AST in the I/R group were higher than those in the SO group (P<0.01). The histological changes were in accord with hepatic I/R injury. CONCLUSION: ALT and AST in serum are closely related to hepatic I/R injury and inflammatory reaction. TNF-alpha production in the liver triggers hepatic I/R injury through a cascade.

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na^+ channels of cortical neurons is time-and dose-dependent

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.

Oxygen-glucose deprivation of neurons transfected with toll-like receptor 3-siRNA Determination of an optimal transfection sequence

Toll-like receptor 3 protein expression has been shown to be upregulated during cerebral ische- mia/reperfusion injury in rats. In this study, rat primary cortical neurons were subjected to oxy- gen-glucose deprivation to simulate cerebral ischemia/reperfusion injury. Chemically synthesized small interfedng RNA （siRNA）-1280, -1724 and -418 specific to toll-like receptor 3 were transfected into oxygen-glucose deprived cortical neurons to suppress the upregulation of toll-like receptor 3 protein expression. Western blotting demonstrated that after transfection with siRNA, toll-like re- ceptor 3 protein expression reduced, especially in the toll-like receptor 3-1724 group. These results suggested that siRNA-1724 is an optimal sequence for inhibiting toll-like receptor 3 expression in cortical neurons following oxygen-glucose deprivation.

Relationship between the burden of pneumocystis carinii, the inflammatory reaction and lung injury in pneumocystis carinii pneumonia

To study the relationship between the burden of Pneumocystis carinii (P carinii) and the inflammatory reaction and biochemical markers in bronchoalveolar lavage fluids (BALF)in a rat model of P carinii pneumonia (PCP) Methods Clean grade 50 male Sprague Dawley rats were immunosuppressed by a subcutaneous injection of 25mg cortisone acetate twice a week for 8-12 weeks; the PCP model was successfully induced in 14 rats The inflammatory reaction and biochemical markers of the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and type Ⅳ collagenase (matrix metalloproteinases, MMP 2, MMP 9) as well as the values of total protein (TP) and albumin (ALB) in BALF between the mild burden group of P carinii (involved alveoli <25% per 100 alveoli, Group A) and the moderate to severe burden group (involved alveoli ≥25% per 100 alveoli, Group B) were measured The other six clean grade SD rats served as normal control group (Group C) Results The total white cell count in BALF was higher in Group B [(6 8±1 7)×10 6/L] than in Group A [(3 8±1 2)×10 6/L] ( P <0 01); however, there were no differences in white cell differentiation Assays of biochemical markers showed that ALB in BALF in Group B (0 893±0 469?g/L) was increased in comparison with Group A (0 262±0 169 ?g/L); it was only 0 026±0 021?g/L in Group C The contents of TP and activities of LDH were higher in Group B (TP 1 756±0 706?g/L, LDH 2580±550?U/L) than in Group A (TP 0 784±0 553?g/L, LDH 1410±620?U/L); the values of TP and LDH were 0 063±0 020?g/L and 370±250?U/L respectively in Group C The activity of Type Ⅳ collagenase, including MMP 2 and MMP 9, was higher in Group B than in Group A ( P <0 01) (MMP 2: 1102±169 grey value vs 459±274 grey value; MMP 9: 1218±257 grey value vs 449±225 grey value) There was no activity of Type Ⅳ collagenase in BALF of Group C No statistically significant difference was observed in ALP between the groups B and A Conclusions These results indicate that there is a significant correlation between the burden of P carinii in lung tissues and the inflammatory reaction as well as biochemical markers of the resultant activity of lung injury

Protective effect and mechanisms of action of Mongolian medicine Sulongga-4 on pyloric ligation-induced gastroduodenal ulcer in rats

BACKGROUND Sulongga-4(SL-4)is a herbal formula used in traditional Mongolian medical clinics for the treatment of peptic ulcers and gastroenteritis,even though its pharmacological mechanism has not been well characterized.AIM To evaluate the protective effect and identify the mechanisms of action of SL-4 on gastroduodenal ulcer induced by pyloric ligation(PL)in rats.METHODS PL was performed to induce gastric and duodenal ulcers in rats,which were then treated with oral SL-4(1.3,2.6,or 3.9 g/kg per day)for 15 d.PL-induced gastroduodenal ulceration.Therapeutic effects were characterized by pathological and histological evaluations and inflammatory indicators were analyzed by enzyme-linked immunosorbent assay.Microarray analyses were conducted to identify gene expression profiles of gastroduodenal tissue in PL rats with or without SL-4 treatment.The candidate target genes were selected and verified by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RESULTS SL-4 decreased histopathological features in the PL-induced ulcerated rats.SL-4 significantly (P < 0.05) decreased expression of tumor necrosis factor-α,interleukin (IL)-1β, IL-6, endotoxin, platelet-activating factor, and increasedprostaglandin E2 and epidermal growth factor in ulcer tissue. Microarray analysiswas used to identify a panel of candidate target genes for SL-4 acting on PLinducedulceration. Genes included some complement and coagulation cascadeand retinol metabolism pathways that are closely associated with inflammatoryresponses and gastric mucosal protective mechanisms. qRT-PCR showed thataltered expression of the selected genes, such as CYP2b2, UGT2b1, A2m, andMASP1 was consistent with the microarray results.CONCLUSIONSL-4 exerts protective effects against PL-induced gastroduodenal ulcers viareducing inflammatory cytokines and elevating expression of gastric acidinhibitory factors. Downregulation of CYP2b2 and UGT2b1 genes in retinolmetabolism and upregulation of A2m and MASP1 genes in the complement andcoagulation cascades pathways are possibly involved in SL-4-mediated protectionagainst gastroduodenal ulcer.

Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.