Objective To evaluate the bacteriostatic effect of recombinant human lactoferrin(rhLF) on Helicobacter(H .) py‐lori and its influence on CagA ,Ure and gastric mucosal IL‐8 .Methods The minimum inhibitory concentration(MIC)and the influ‐ence of different drug concentrations on the proliferation of H .pylori were detected .The effects of rhLF on the mRNA and protein expressions of CagA and Ure in H .pylori were detected by RT‐PCR and Western blot ,respectively .The animal study :Balb/c mice were adopted and assigned randomly into four groups ,including the standard triple+rhLF(group A) ,rhLF(group B) ,standard tri‐ple(group C) and normal saline(group D) .The histopathological HE staining was used to observe the gastric inflammation and ELISA was used to detect the IL‐8 level of gastric tissue in each group .Results MIC was 0 .5 mg/mL ,moreover rhLF inhibited the bacterial growth and proliferation with a concentration‐dependent manner .rhLF could reduce the expression of H .pylori major viru‐lence factor CagA ,mRNA and protein of Ure .Comparing the group A with the group B ,C and D ,the gastric mucosal inflammation score and the IL‐8 levels of gastric tissue homogenates had statistically significant differences(P<0 .05) .Conclusion rhLF inhibits the growth and proliferation of H .pylori ,moreover inhibit the expression of major virulence factor CagA in H .pylori ,mRNA and protein of Ure in different degrees ,weakens its pathogenicity ,meanwhile reduces the IL‐8 level in mice gastric mucosa ,and allevi‐ates H .pylori related gastric mucosal inflammatory response .

Objective:To investigate the modulatory function of interleukin-7 (IL-7)/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis (MG). Methods:Fifty-seven treatment-naive MG patients who were hospitalized in Department of Neurology, Nanyang Central Hospital between 2017 and 2020 as well as 35 healthy controls were enrolled. Peripheral blood was collected, while plasma and peripheral blood mononuclear cells were isolated. Plasma IL-7 and soluble CD 127 (sCD 127) were measured by enzyme linked immunosorbent assay (ELISA). Membrane-bound CD 127 (mCD 127) percentage in CD 8+T cells was measured by flow cytometry. The differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type and their correlation with Quantitative Myasthenia Gravis (QMG) score were analyzed. Purified CD 8+T cells from MG patients were stimulated with recombinant human IL-7 (5 μg/L). Changes of sCD 127 and mCD 127 level were analyzed. Levels of perforin, granzyme B, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the cultured supernatants were measured by ELISA. Immune checkpoint molecules mRNA in CD 8+T cells was semi-quantified by real-time fluorescence quantitative polymerase chain reaction. Results:Plasma IL-7 level was up-regulated in MG patients compared with controls [(293.4±74.7) pg/ml vs (233.8±70.8) pg/ml, t=3.78, P<0.001], while sCD 127 level was down-regulated in MG patients compared with controls [(102.7±13.7) pg/ml vs (131.2±20.9) pg/ml, t=7.91, P<0.001]. Peripheral CD 8+T cells percentage was up-regulated in MG patients compared with controls (35.4%±7.1% vs 30.2%±7.5%, t=3.31, P=0.001), and mCD 127+CD 8+T cell percentage was also elevated (45.5%±7.7% vs 34.7%±11.5%, t=5.44, P<0.001). There were no significant differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type. There was no significant correlation between above indices and QMG score. There were no significant differences of sCD 127 in cultured supernatants, mCD 127+CD 8+T cell percentage, or immune checkpoint molecules mRNA expression between CD 8+T cells from MG patients with and without IL-7 stimulation. IL-7 stimulation promoted the secretion of perforin [(208.1±67.2) pg/ml vs (168.8±46.2) pg/ml, t=2.16, P=0.038], granzyme B [(941.8±273.9) pg/ml vs (782.4±137.2) pg/ml, t=2.33, P=0.025], and IFN-γ [(19.1±5.2) pg/ml vs (15.3±4.5) pg/ml, t=2.47, P=0.018] by CD 8+T cells. However, there was no remarkable difference of TNF-α production between CD 8+T cells with and without IL-7 stimulation. Conclusion:Elevated IL-7-mediated signaling pathway enhanced the secretion of cytotoxic molecules and cytokines by CD 8+T cells, leading to increased activity of CD 8+T cells in MG patients.

Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor(SGLT2i)canagliflozin and epithelial sodium channel inhibitor amiloride or benzamil in combination on the bone metabolism in the rats with the nephrotic syndrome(NS)induced by doxorubicin.Methods In the 49 male SD rats selected,7 were randomly selected as control group(NG),and 42 were built as adria-mycin-induced nephropathy model by injecting adriamycin through the tail vein,and were randomly di-vided into model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),canagliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 cases in each group.Each medication group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.The 24-hour urinary protein(24 h-UTP)of each group was detected one day before treatment to verify the successful preparation of the model.At 6 weeks after treatment,the 24 h-UTP,urine sodium(UNa),urinary potassium(UK)levels in urine and the albumin(ALB),triglyceride(TG),cholesterol(TC),low density lipoprotein(LDL),serum calcium(SCa),sodium(SNa),potassium(SK),25-hydroxyvitamin D(25-OH-D),alkaline phosphatase(ALP),parathyroid hormone(PTH),procollagen type ⅠN-terminal propeptide(PINP)and beta C-terminal cross-linked telopeptides of type Ⅰ collagen(β-CTX)levels in serum were measured,respectively.Results After successful modeling,the levels of 24 h-UTP,TG,TC,LDL and SCa in the MG group were significantly increased,while the levels of ALB,25-OH-D,ALP,PINP and PTH were significantly decreased(P＜0.05 or P＜0.01).After 6 weeks of drug intervention,the body mass of rats treated with KG alone decreased significantly(P＜0.05).Compared with the MG group,the levels of 24 h-UTP,TC,TG,LDL and SCa were significantly decreased,and the level of ALB was significantly increased in all drug groups when compared to the MG(P＜0.05 or P＜0.01).Compared with the MG group,the levels of 25-OH-D,ALP,PINP and β-CTX in the KA group were significantly increased when compared to the MG(P＜0.05 orP＜0.01).Molding and drug therapy had no impact on levels of UNa,UK,SK and SNa(P＞0.05).Conclusion Calaglizin alone,benzamil alone,amiloride alone and cala-glizin combined with benzamil or amiloride can improve the mass proteinuria,hypoproteinemia and hyperlipidemia in adriamycin-induced NS model rats.The combination of caraglipzin and amiloride has a significant osteogenic or osteoclastic effect,which may play a role in reducing the risk of frac-ture in NS rats by forming a new osteogenic/osteoclastic balance.

Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor(SGLT2i)canagliflozin and epithelial sodium channel inhibitor amiloride or benzamil in combination on the bone metabolism in the rats with the nephrotic syndrome(NS)induced by doxorubicin.Methods In the 49 male SD rats selected,7 were randomly selected as control group(NG),and 42 were built as adria-mycin-induced nephropathy model by injecting adriamycin through the tail vein,and were randomly di-vided into model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),canagliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 cases in each group.Each medication group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.The 24-hour urinary protein(24 h-UTP)of each group was detected one day before treatment to verify the successful preparation of the model.At 6 weeks after treatment,the 24 h-UTP,urine sodium(UNa),urinary potassium(UK)levels in urine and the albumin(ALB),triglyceride(TG),cholesterol(TC),low density lipoprotein(LDL),serum calcium(SCa),sodium(SNa),potassium(SK),25-hydroxyvitamin D(25-OH-D),alkaline phosphatase(ALP),parathyroid hormone(PTH),procollagen type ⅠN-terminal propeptide(PINP)and beta C-terminal cross-linked telopeptides of type Ⅰ collagen(β-CTX)levels in serum were measured,respectively.Results After successful modeling,the levels of 24 h-UTP,TG,TC,LDL and SCa in the MG group were significantly increased,while the levels of ALB,25-OH-D,ALP,PINP and PTH were significantly decreased(P＜0.05 or P＜0.01).After 6 weeks of drug intervention,the body mass of rats treated with KG alone decreased significantly(P＜0.05).Compared with the MG group,the levels of 24 h-UTP,TC,TG,LDL and SCa were significantly decreased,and the level of ALB was significantly increased in all drug groups when compared to the MG(P＜0.05 or P＜0.01).Compared with the MG group,the levels of 25-OH-D,ALP,PINP and β-CTX in the KA group were significantly increased when compared to the MG(P＜0.05 orP＜0.01).Molding and drug therapy had no impact on levels of UNa,UK,SK and SNa(P＞0.05).Conclusion Calaglizin alone,benzamil alone,amiloride alone and cala-glizin combined with benzamil or amiloride can improve the mass proteinuria,hypoproteinemia and hyperlipidemia in adriamycin-induced NS model rats.The combination of caraglipzin and amiloride has a significant osteogenic or osteoclastic effect,which may play a role in reducing the risk of frac-ture in NS rats by forming a new osteogenic/osteoclastic balance.

Objective To analyze the effects of massage therapy on the inflammatory state and lung function of pediatric refractory Mycoplasma pneumonia(RMPP).Methods A total of 320 chil-dren with RMPP treated in Hebei Seventh People's Hospital from September 2022 to August 2023 were selected in the study.According to different treatment methods,they were divided into two groups,with 160 cases in each group.The western medicine group was given conventional anti-in-flammatory and other symptomatic treatment,while the massage group was given dialectical massage treatment based on the western medicine group.The clinical efficacy,duration of disappearance of clinical symptoms,pulmonary function indexes,serum inflammatory factors,immune function indexes and total incidence of adverse reactions were compared between the two groups.Results The total effective rate of massage group was higher than that of control group(P＜0.05).The disappearance time of fever,cough,sputum and lung moist rales in observation group was shorter than that in control group(P＜0.05).After treatment,the peak expiratory flow(PEF),maximum mid-expiratory flow(MMEF)and forced vital capacity(FVC)in the massage group were higher than those in the control group(P＜0.05).The levels of serum C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the massage group were lower than those in the control group after treatment(P＜0.05).After treatment,CD3+,CD4+,CD4+/CD8+in the massage group were higher than those in the control group(P＜0.05),and CD8+was lower than that in the control group(P＜0.05).There was nosignificant difference in the total incidence of adverse reactions between the massage group and the western medicine group(P＞0.05).Conclusion Massage based on syndrome differentiation combined with western medicine can effectively relieve fever,cough and other symptoms of RMPP children,reduce inflammatory response,improve lung function and immune function,and has less adverse reactions.

Objective To analyze the effects of massage therapy on the inflammatory state and lung function of pediatric refractory Mycoplasma pneumonia(RMPP).Methods A total of 320 chil-dren with RMPP treated in Hebei Seventh People's Hospital from September 2022 to August 2023 were selected in the study.According to different treatment methods,they were divided into two groups,with 160 cases in each group.The western medicine group was given conventional anti-in-flammatory and other symptomatic treatment,while the massage group was given dialectical massage treatment based on the western medicine group.The clinical efficacy,duration of disappearance of clinical symptoms,pulmonary function indexes,serum inflammatory factors,immune function indexes and total incidence of adverse reactions were compared between the two groups.Results The total effective rate of massage group was higher than that of control group(P＜0.05).The disappearance time of fever,cough,sputum and lung moist rales in observation group was shorter than that in control group(P＜0.05).After treatment,the peak expiratory flow(PEF),maximum mid-expiratory flow(MMEF)and forced vital capacity(FVC)in the massage group were higher than those in the control group(P＜0.05).The levels of serum C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the massage group were lower than those in the control group after treatment(P＜0.05).After treatment,CD3+,CD4+,CD4+/CD8+in the massage group were higher than those in the control group(P＜0.05),and CD8+was lower than that in the control group(P＜0.05).There was nosignificant difference in the total incidence of adverse reactions between the massage group and the western medicine group(P＞0.05).Conclusion Massage based on syndrome differentiation combined with western medicine can effectively relieve fever,cough and other symptoms of RMPP children,reduce inflammatory response,improve lung function and immune function,and has less adverse reactions.

AIM:To analyze the occurrence and clinical characteristics of adverse drug reactions(ADR)induced by four programmed cell death pro-tein 1(PD-1)inhibitors according to literature re-ports,and to provide reference for clinical safe medication.METHODS:PubMed,CNKI,and Wan-fang,and other databases were searched to collect case reports of adverse reactions caused by four PD-1 inhibitors,including camrelizumab,sintilimab,toripalimab,and tislelizumab.RESULTS:A total of 105 eligible literature reports were retrieved from the databases at home and abroad(as of June 1,2022),including 42 reports on camrelizumab with 47 patients,29 reports on sintilimab with 30 pa-tients,21 reports on toripalimab with 24 patients and 13 reports on tislelizumab with 15 patients.Among them,there were 76 males(65.5％)and 40 females(34.5％),with a gender ratio of 1.9:1.0.The age range was between 29 to 84 years old,and the onset of ADR mainly occurred within 4 months af-ter the first use of PD-1 inhibitors.Immune-related adverse reactions were mainly manifested as skin and its attachment(41 cases,34.5％),endocrine sys-tem(25 cases,21.0％),and cardiovascular system(22 cases,18.5％).Most patients improved after symptomatic and supportive treatment.CONCLU-SION:Immune-related adverse effects(irAEs)may occur at any time during treatment with the four PD-1 inhibitors,among these the skin system is most frequently affected,followed by the cardiovas-cular and endocrine systems.This suggests the im-portance of individualized drug administration and stringent control over indications in clinical prac-tice.Close monitoring throughout immunotherapy is essential to minimize or prevent irAEs,thus en-suring patient safety in medication usage.