Serum OPN and NF-κB contents in children with Henoch-Schonlein purpura and their correlation with oxidative stress and cellular immune function

Objective:To detect serum OPN and NF-κB contents in children with Henoch-Schonlein purpura (HSP) and study their correlation with oxidative stress and cellular immune function. Methods: The children who were diagnosed with HSP in Shijiazhuang First Hospital between February 2015 and October 2017 were selected as the HSP group of the study and the healthy children who received physical examination during the same period were selected as the control group. The serum was collected to measure the contents of OPN, NF-κB, oxidative stress indexes and immune cell inflammation, and the peripheral blood was collected to detect the mRNA expression of immune cell transcription factors.Results: OPN, NF-κB, MDA, MPO, IL-4, IL-5 and IL-17 contents in serum as well as GATA-3 and RORγt mRNA expression in peripheral blood of HSP group were significantly higher than those of control group whereas SOD, CAT, PON, IFN-γ and TGF-β1 contents in serum as well as T-bet and FoxP3 mRNA expression in peripheral blood were significantly lower than those of control group;serum OPN and NF-κB contents in HSP group were positively correlated with MDA, MPO, IL-4, IL-5 and IL-17 contents in serum as well as GATA-3 and RORγt mRNA expression in peripheral blood, and negatively correlated with SOD, CAT, PON, IFN-γand TGF-β1 contents in serum as well as T-bet and FoxP3 mRNA expression in peripheral blood. Conclusion: The abnormal increase of serum OPN and and NF-κB contents in children with HSP is closely related to the excessive oxidative stress activation and cellular immune dysfunction.

Effects of SOCS1 and SOCS3 in peripheral blood on CD4+T cell differentiation in children with Henoch-Schonlein purpura

Objective:To study the effects of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in peripheral blood on CD4+T cell differentiation in children with Henoch-Schonlein purpura. Methods: Children with Henoch-Schonlein purpura who were treated in Zigong Maternal and Child Health Hospital between June 2014 and February 2018 were selected as the HSP group of the study, and healthy children who received physical examination during the same period were selected as the control group of the study. Peripheral blood was collected to determine the expression of SOCS1 and SOCS3 as well as the contents of CD4+T cell subsets, and serum was collected to determine the contents of CD4+T cytokines.Results: SOCS1 and SOCS3 mRNA expression levels as well as SOCS3/SOCS1 ratio in peripheral blood of HSP group were significantly higher than those of control group;Th1 and Treg contents in peripheral blood as well as IFN-γ and TGF-β1 contents in serum of HSP group were lower than those of control group whereas Th2 and Th17 contents in peripheral blood as well as IL-4, IL-5 and IL-17 contents in serum were higher than those of control group, and Th1 and Treg contents in peripheral blood as well as IFN-γ and TGF-β1 contents in serum of HSP children with high SOCS3/SOCS1 ratio were lower than those of HSP children with low SOCS3/SOCS1 ratio whereas Th2 and Th17 contents in peripheral blood as well as IL-4, IL-5 and IL-17 contents in serum were higher than those of HSP children with low SOCS3/SOCS1 ratio.Conclusions: Changes in SOCS1 and SOCS3 expression in peripheral blood of children with Henoch-Schonlein purpura can affect the differentiation of CD4+T cells.

Delayed diagnosis of abdominal Henoch-Schonlein purpura in children:A case report

BACKGROUND For children with abdominal Henoch-Schonlein purpura presenting abdominal pain as an initial symptom and severe clinical manifestations,but without purpura appearance on the skin,the diagnosis and treatment are relatively difficult.This study summarized the characteristics of this group of patients by literature review and provided additional references for further refinement of glucocorticoid therapy in this vasculitis.CASE SUMMARY A 6-year-old girl presented mainly with repeated abdominal pain and had received short-term out-of-hospital treatment with hydrocortisone.On day 7 after onset,gastroscopy revealed chronic non-atrophic gastritis and erosive duodenitis without purpuric rash,and no obvious resolution of the abdominal pain was found after treatment against infection and for protection of gastric mucosa.On day 14 the inflammatory indices continued to rise and the pain was relieved after enhanced anti-infective therapy,but without complete resolution.On day 19,the patient presented with aggravated abdominal pain with purplish-red dots on the lower limbs,by which Henoch-Schonlein purpura was confirmed.After 5 d of sequential treatment with methylprednisolone and prednisone,abdominal pain disappeared and she was discharged.CONCLUSION Henoch-Schonlein purpura-related rash may appear after long-term abdominal pain,and should be distinguished from acute and chronic gastrointestinal diseases at the early stage without typical rash.For bacterial infection-induced Henoch-Schonlein purpura,glucocorticoid therapy alone without clearing the infection may not relieve symptoms.

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

Helicobacter pylori(H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extraintestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura(HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum Ig A, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.

Spectrum of Henoch-Schonlein Purpura in Children: A Single-Center Experience from Western Provence of Saudi Arabia

The aim of this study was to describe the common presentation, frequency, and complications of Henoch-Schonlein purpura (HSP) in patients <18 years who were followed up at King Abdulaziz University Hospital, Jeddah over the last 12 years. We performed a retrospective chart review of the medical records of all patients diagnosed as HSP. During this period, only 29 cases were reported (15 males, 14 females), with the mean age at the diagnosis 7.5 years. 82% percent of the patients had joint involvement in the form of arthritis or arthralgia;17.2% had no joint involvement. Abdominal manifestations were reported in 72.4% of the patients, while renal involvement was documented in 24.1% of the cases;two patients had scrotal involvement. Four patients (13.7%) had a recurrence within four months of HSP diagnosis. However, all patients had full recovery within a month. More research is warranted to study the prevalence, clinical manifestations, preceding factors, and complications of HSP in a Saudi-based cohort.

Effects of methylprednisolone combined with montelukast on immune function and cytokines in children with recurrent Henoch-Schonlein purpura

Objective:To study the effects of methylprednisolone combined with montelukast on immune function and cytokines in children with recurrent Henoch-Schonlein purpura.Methods:Children who were diagnosed with recurrent Henoch-Schonlein purpura in Zigong Third People's Hospital between September 2015 and August 2017 were selected as the research subjects and randomly divided into the intervention group who received methylprednisolone combined with montelukast therapy and the control group who received hydrocortisone therapy. The levels of Th1/Th2 and Th17/Treg immunity indexes in peripheral blood as well as cytokines in serum were measured before treatment as well as 4 and 8 weeks after treatment.Results: 4 weeks and 8 weeks after treatment, Th1 and Treg cell contents as well as T-bet and FoxP3 mRNA expression in peripheral blood of both groups of patients were significantly higher than those before treatment whereas Th2 and Th17 cell contents as well as GATA-3 and RORγt mRNA expression in peripheral blood and NF-κB, OPN, IL-33, MK and HMGB1 contents in serum were significantly lower than those before treatment, and Th1 and Treg cell contents as well as T-bet and FoxP3 mRNA expression in peripheral blood of intervention group were significantly higher than those of control group whereas Th2 and Th17 cell contents as well as GATA-3 and RORγt mRNA expression in peripheral blood and NF-κB, OPN, IL-33, MK and HMGB1 contents in serum were significantly lower than those of control group.Conclusion: methylprednisolone combined with montelukast treatment of recurrent Henoch-Schonlein purpura can regulate the immune function and inhibit the cytokine secretion.

Overview of the pathogenesis of Henoch-Schonlein purpura in children and the research progress on related mechanism of inflammatory cytokines

Henoch-schonlein purpura (HSP) is a kind of systemic vasculitis that is common in childhood,and its pathogenesis is complicated and considered to have important relationship with lymphocytes, vascular endothelial cells and so on. The causes of this disease are complex and have not been clearly identified, but numerous studies have shown that inflammatory factors such as IL-1, IL-17 and TNF-α play an important role in the development of HSP.

Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: A case report

Henoch-Schonlein purpura (HSP) with intestinal perforation and cerebral hemorrhage is a very rare clinical condition. There has been no report of HSP complicated with both intestinal perforation and cerebral hemorrhage until October 2012. Here we describe a case of HSP with intestinal perforation and cerebral hemorrhage in a 5-year-old girl. Plain abdominal radiograph in the erect position showed heavy gas in the right subphrenic space with an elevated diaphragm. Partial resection of the small intestine was performed, and pathological analysis suggested chronic suppurative inflammation in all layers of the ileal wall and mesentery. Seventeen days after surgery, cerebral hemorrhage developed and the patient died.

Endoscopic findings in a patient with Henoch-Schonlein purpura

Henoch-Schonlein purpura (HSP) is a systemic vasculitis of the small vessels of the skin, joints, GI tract, and kidney. It preferentially affects children but may also occur in adults. We report a 60-year-old man with HSP who presented with colicky abdominal pain, bloody diarrhea, arthralgia, and skin rash. The gastrointestinal tract was viewed by upper endoscopy and colonoscopy. We found characteristic endoscopic findings in the stomach, cecum and sigmoid colon, the combination of which has rarely been demonstrated in one patient. Histologic examination of skin biopsy specimens revealed leukocytoclastic vasculitis with positive staining for IgA in the capillaries. Endoscopy appears to have substantial diagnostic utility in patients suspected of having HSP, especially when abdominal symptoms precede the cutaneous lesions.

Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

Henoch-Schonlein purpura(HSP) is a small vessel vasculitis mediated by type Ⅲ hypersensitivity with deposition of Ig A immune complex in the walls of vessels. It is a multi-system disorder characterizedby palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP.

Henoch-Schonlein purpura from vasculitis to intestinal perforation: A case report and literature review

Henoch-Sch?nlein purpura(HSP) is generally a selflimited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrastenhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications.

Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis

This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.

Efficacy Analysis of Glucocorticoids in the Treatment of Allergic Purpura in Tibetan Children

Background: Henoch Schonlein Purpura (HSP) is a common immune-related allergic disease in children. It is very important to understand the clinical features of this disease for doctors. Objective: To explore the clinical efficacy of glucocorticoids in the treatment of HSP in Tibetan children at high altitude, and to analyze the possible causes of HSP in children at high altitude. The risk factors of the disease provide a reference for the treatment of HSP in children in high altitude areas. Methods: Selecting January 2015 to November 2020, 88 children diagnosed with Henoch-Schonlein Purpura in the outpatient and inpatient departments of the People’s Hospital of Bomi County, Tibet Autonomous Region were the subjects of the study. Its gender, age of onset, season of onset, predisposing factors, allergy history, first symptoms, clinical manifestations, laboratory examinations, etc., perform retrospective analysis. Results: Among 88 children with allergic purpura, 55 were boys, accounting for 62.5%, and 33 were girls, accounting for 37.5%. Men have more cases than women. All have clinical manifestations of purpura of the skin, among which 35 cases have obvious triggers, of which the above there were 26 cases of respiratory infections, 6 cases of dietary factors, and 3 cases of contact with allergic substances. Simple skin type: 18 cases, accounting for 20.45%;Abdominal type: 6 cases, accounting for 6.82%;2 male cases, accounting for 33.33%;4 female cases, accounting for 66.67%;Articular type: 8 cases, accounting for 33.33%;Renal type: 2 cases, accounting for 2.27%;54 cases of mixed type, accounting for 61.36%. After glucocorticoids, the rashes disappeared, no any adverse reactions. Conclusion: Allergic purpura in children is more common in school-age children, and upper respiratory tract infection is the main predisposing factor. Skin purpura is the main clinical manifestation, often associated with lower extremity joint swelling and pain. There is no significant difference in the efficacy and course of the disease between intravenous and oral treatment. Therefore, clinicians should strictly grasp the indications of glucocorticoids to reduce the occurrence of complications.

Risk factors for intussusception in children with Henoch-Schönlein purpura:A case-control study

BACKGROUND The etiology of Henoch-Schönlein purpura(HSP)with intussusception remains undefined.AIM To investigate the risk factors for intussusception in children with HSP and gastrointestinal(GI)involvement.METHODS Sixty children with HSP and concomitant intussusception admitted to the Beijing Children’s Hospital of Capital Medical University between January 2006 and December 2018 were enrolled in this study.One hundred pediatric patients with HSP and GI involvement but without intussusception,admitted to the same hospital during the same period,were randomly selected as a control group.The baseline clinical characteristics of all patients,including sex,age of onset,duration of disease,clinical manifestations,laboratory test results,and treatments provided,were assessed.Univariate and multiple logistic regression analyses were performed to identify possible risk factors.RESULTS The 60 children in the intussusception group comprised 27 girls(45%)and 33 boys(55%)and the 100 children in the non-intussusception group comprised 62 girls(62%)and 38 boys(38%).The median age of all patients were 6 years and 5 mo.Univariate and multiple regression analyses revealed age at onset,not receiving glucocorticoid therapy within 72 h of emergence of GI symptoms,hematochezia,and D-dimer levels as independent risk factors for intussusception in children with HSP(P<0.05).CONCLUSION The four independent risk factors for intussusception in pediatric HSP with GI involvement would be a reference for early prevention and treatment of this potentially fatal disease.

Regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on data mining techniques

Objective:This study aims to explore the regularity of syndrome differentiation and treatment of traditional Chinese medicine(TCM)for allergic purpura.Methods:CNKI,Weipu Chinese science and technology database,wanfang medical network database,and Chinese biomedical literature database were searched for eligible studies.Medical records including complete patient personal information,patient symptoms,TCM syndromes,treatment,and medication were included.The data was analyzed using the Chinese medicine heritage support platform provided by the Chinese Academy of Chinese medicine(V2.5).Results:Differentiation of health gas camp blood was the most commonly used method of differentiation of symptoms and signs in famous veteran TCM.The treatment included cooling blood,activating blood circulation,clearing heat and detoxifying toxins,removing blood stasis and stopping bleeding.Honeysuckle,Forsythia suspensa,cicada slough and other drugs were interrelated.Potential drug pair combinations and drug networks showed the basic drug composition of Qingying Decoction.According to the entropy cluster analysis,28 core drug combination and 12 new formulations were obtained.Conclusion:The regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on the famous and old TCM doctors was complex.Further researches are still needed.

Evaluation of the cytokine levels and immune response status of montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura

Objective:To evaluate the cytokine levels and immune response status of montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura.Methods: A total of 80 patients with Henoch-Schonlein purpura who were treated in Ankang Central Hospital between May 2014 and January 2017 were collected and divided into montelukast group, loratadine group, tanshinone group and combined treatment group according to the random number table, 20 cases in each group. Serum levels of inflammatory factors, Th17/Treg cellular immunity indexes before and after treatment were compared among four groups of patients.Results: Before treatment, differences in serum levels of inflammatory factors and Th17/Treg cellular immunity indexes were not statistically significant among four groups of patients. After treatment, serum HMGB1, IL-8, IL-14, IL-23 and IL-33 levels in combined treatment group were lower than those in montelukast group, loratadine group and tanshinone group;serum IL-17 level was lower than that in montelukast group, loratadine group and tanshinone group while IL-10 and TGF-β levels were higher than those in montelukast group, loratadine group and tanshinone group.Conclusions: Montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura helps to reduce systemic inflammatory response and balance Th17/Treg cell immunity.

Expressions and significances of IFN-γ, IL-10, TGF-β, PFP and GNLY in serum of children with Henoch Schonlein purpura

Objective:To investigate the expressions of interferon-γ (IFN-γ), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), perforin (PFP) and granulysin (GNLY) in serum of children with Henoch-Schonlein purpura (HSP) and their significances.Methods: 86 children with HSP admitted to our hospital from April 2016 to April 2018 were selected as the study subjects (HSP group), according to whether or not combined with renal injury, they were divided into kidney injury group (41 cases) and non-kidney injury group (45 cases), and 40 healthy children as the control group. The levels of serum IFN-γ, IL-10 and TGF-β were detected by enzyme-linked immunosorbent assay (ELISA), levels of serum PFP and GNLY were detected by RT-PCR, the differences between different groups were compared, the relationships between serum IFN-γ, IL-10, TGF-β, PFP and GNLY in group HSP was also analyzed.Results: The levels of serum IFN-γ, PFP and GNLY in HSP group were lower than those in control group (P<0.05), and the levels of serum IL-10 and TGF-β were higher than those in control group (P<0.05);the levels of serum IFN-γ, PFP and GNLY in renal injury group were lower than those in non-renal injury group (P<0.05), while the levels of serum IL-10 and TGF-β were higher than those in non-renal injury group (P<0.05);in HSP group, serum IFN-γ was negatively correlated with TGF-β (r=-0.417,P=0.037), and positively correlated with PFP and GNLY (r=0.508, 0.477,P=0.025, 0.030);there was a positive correlation between IL-10 and TGF-β (r=0.514,P=0.017).Conclusion: The changes of serum IFN-γ, IL-10, TGF-β, PFP and GNLY are closely related to the occurrence and progression of HSP, early detection is helpful to the evaluation of HSP and has guiding significance for clinical prevention of Henoch-Schonlein purpura nephritis.

Effect of tanshinone on blood coagulation, inflammatory factors and immune function in children with allergic purpura

Objective:To investigate the effects of tanshinone treatment on coagulation function, inflammatory factors and immune function in children with allergic purpura, and to guide clinical medication.Methods:130 children with allergic purpura diagnosed in a certain hospital from November 2015 to June 1818 were selected. According to the random number table method, they were divided into control group and study group, 65 cases in each group. The control group was given conventional anti-allergic drugs, and the study group was treated with tanshinone on the basis of the control group. The changes of renal function, inflammatory factors, coagulation function and immune function were compared between the two groups before and after treatment.Result:There were no significant differences in renal function, inflammatory factors, coagulation function and immune function between the two groups (P>0.05). After treatment, the levels of renal function Scr, BUN and Cysc and were significantly decreased in the two groups, and the inflammatory factors PCT, CRP levels were significantly decreased in the two groups (P<0.05). The above indexes of the study group were significantly lower than the control group (P<0.05). After treatment, APTT and PT levels were significantly increased in both groups, and FIB and ESR levels were significantly lower (P<0.05). The levels of APTT and PT in the study group were significantly higher than those in the control group, and the FIB and ESR level was significantly lower than that in the control group (P<0.05). After treatment, the levels of IgG, C3 and C4 were significantly lower in the two groups (P<0.05). The levels of IgG, C3 and C4 in the study group were significantly lower than those in the control group (P<0.05).Conclusion: Tanshinone combined with anti-allergic drugs has significant curative effects on children with Henoch-Schonlein purpura. It can significantly reduce renal function damage, alleviate inflammation stress response, improve coagulation function and correct immune disorders. And it is worthy of clinical application.

A treatment for Henoch-Schonlein purpura based on Shaoyang Channels： a hypothesis and case report

Henoch-Schonlein purpura （HSP） is an IgA-mediated vasculitis which is easy to relapse. A lot of patients have to useglucocorticoids, immunosuppressive drugs and other drugs which will bring sorts of serious side effects. Unfortunately,most of patients have to face the hurt of abdominal pain, arthritis, purpuric rash and renal involvement again after relapse.We have used Xiaochaihu decoration which is a famous formula in Shanghanlun to cure most of patients, especially whowith abdominal pain and purpuric rash. Due to the fact that this formula belongs to the Shaoyang Channels, interestingly,we find that these symptoms are located in regions close to the Shaoyang Channels. So that is the reason why Xiaochaihu decoration could work.

紫癜1号方治疗儿童过敏性紫癜性肾炎临床观察

目的:观察紫癜1号方对紫癜性肾炎(HSPN)患儿外周血嗜酸性粒细胞及其凋亡因子Fas蛋白表达的影响。方法:选取2019年10月1日—2020年12月30日于深圳市中医院门诊和住院部诊治的HSPN患儿60例,随机分为观察组和对照组,各30例。观察组予紫癜1号方加减及中药针剂治疗,对照组给予西医常规治疗,2组疗程均为12周。观察治疗前、治疗第0、4、8、12周各时间段的尿N-乙酰氨基葡萄糖苷酶(NAG)、尿微量白蛋白(mALB)、β2-微球蛋白(β2-MG),以及血嗜酸性粒细胞(EOS)、死亡诱导因子(Fas)等变化情况和疗效变化。结果:治疗第4、8周时,观察组总有效率分别为83.33%、96.67%,明显高于对照组,组间比较有显著性差异(P<0.05);第4、8周时,观察组降低患儿NAG的效果显著优于对照组(P<0.01);各个观察时点观察组降低β2-MG的效果均优于对照组(P<0.05);第4、12周时,观察组降低m ALB的效果优于对照组(P<0.05)。治疗第4周时,促进Fas抗原表达、降低EOS的效果对照组优于观察组,差异有统计学意义(P<0.01)。结论:紫癜1号方在早期能改善HSPN患儿临床症状,对改善早期肾损害指标起效更快,作用更持久。