Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

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.

Objective:A SARS-CoV-2 pseudovirus(PsV)system was established for neutralizing antibody evaluation and virus entry inhibitor screening.Methods:Lentiviral vector plasmids psPAX2,pCDH-Luc and SARS-CoV-2 Spike(S)protein expres-sion plasmids were co-transfected,and harvested pseudoviral supernatant was used to infect ACE2-293T cells.Protein content of p24 was determined to reflect titer of PsV,and expression of S protein in PsV was detected by Western blot.Neutralization capacity of an S protein monoclonal antibody was evaluated using original strain,D614G,Gamma,Delta,Omicron PsV.Two reported virus entry inhibitors,chloroquine and carrageenin,were used to detect effect on entry of Omicron PsV.Results:Lentiviral vector successfully incorporated S protein.Western blot results showed that S protein mutated at 665Y showed a different cleavage form(90 kD)than wild-type full-length S protein(180 kD).Titer of PsV packaged by three plasmids system was higher.Ratio of S protein expression plasmid,transfer plasmid and packaging plasmid at 1∶3∶3 was optimum condition for viral packaging.Titer of PsV packaged under this condi-tion was over 20 ng/ml.PsV could effectively infect ACE2-293T cells,and double reporter gene GFP and firefly luciferase were expressed obviously,whose chemiluminescence values reached 106.Monoclonal antibodies of S protein effectively neutralized four types of PsVs,but neutralization of original strain was 10～30 times greater than that of variant PsV.Virus entry inhibitors,chloroquine and ι-carrageenan significantly inhibited entry of Omicron PsV.Conclusion:SARS-CoV-2 PsV infection system we conducted can simu-late entry of SARS-CoV-2 successfully.Effective pharmacodynamic evaluation of neutralizing antibodies and virus entry inhibitors can be performed efficiently by the system,which can provide a technical platform for evaluation of neutralizing antibody of SARS-CoV-2 and screening of virus entry inhibitors,and would benefit R&D of anti-SARS-CoV-2 drugs.

Pyroptosis is a programmed death mediated by activated caspase and Gasdermin family proteins,characterized by cell swelling,cytosolysis and release of inflammatory factors.Leukemia is a malignant disease characterized by abnormal differentiation and proliferation of hematopoietic stem cells,thus seriously threating human health.In recent years,it has been found that the transformation,proliferation,metastasis and treatment response of leukemia cells are closely related to pyrodeath.Pyroptosis provides a new perspective for the study of leukemia.This paper reviews the types and molecular mechanisms of pyroptosis,the role of pyroptosis in the occurrence and development of leukemia and the treatment of leukemia,so as to provide some references for further study of the relationship between pyroptosis and leukemia,in order to provide a new strategy for the treatment of leukemia.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Objective:To investigate the value of serum free light chain(sFLC)and serum calcium ion in the diagnosis and prognosis of multiple myeloma(MM).Methods:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group,and 40 healthy volunteers were selected as the control group.The differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc between the two groups were compared.Meanwhile,the differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc in different international staging systems(ISS),chemotherapy efficacy and prognosis patients were analyzed.Results:The levels of sFLC-κ[(98.39±21.19)vs(12.01±4.45)mg/L],sFLC-λ[(210.20±45.54)vs(14.10±5.11)mg/L]and proportions of hypocalcemia(65％vs 0)in the observation group were significantly higher than those in the control group(P＜0.05),while sFLC-κ/λ ratio[(0.44±0.10)vs(0.87±0.12)]and serum calcium ions[(1.98±0.46)vs(2.42±0.40)mmol/L]were significantly lower than those in the control group(P＜0.05).The sFLC-κ,sFLC-λ,the proportion of hypocalcemia and the course of hypocalcemia in ISS stage Ⅲ patients in the observation group were significantly higher than those in stage Ⅰ and Ⅱ patients(P＜0.05),while sFLC-κ/λ ratio,and serum calcium ions were significantly lower than those in stage Ⅰ and Ⅱ patients(P＜0.05).The levels of sFLC-κ[(107.76±21.22)vs(94.67 ±20.11)mg/L],sFLC-λ[(245.54±41.12)vs(205.54±50.22)mg/L]of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia[(0.42±0.04)vs(0.47±0.06);P＜0.05].The levels of sFLC-κ[(107.29±20.14)vs(91.11±18.92)mg/L],sFLC-λ[(247.98±42.26)vs(179.29±39.32)mg/L]in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy[(0.43± 0.10)vs(0.50±0.09);P＜0.05)].The area under the ROC curve for sFLC-κ,sFLC-λ,sFLC-κ/λ predicting ineffective chemotherapy was 0.803,0.793 and 0.699 respectively,P＜0.05.There was no significant difference in sFLC-κ,sFLC-λ,sFLC-κ/λ ratio,serum calcium ion,hypocalcemia ratio and hypocalcemia course between survival and death patients(P＞0.05).Conclusion:sFLC and serum calcium are related to 1SS stage of MM patients.sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients.However,the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

Objective To retrieve,evaluate and summarize the best evidence on the management of ocular complications in intensive care patients ventilated in prone position,and to provide references for clinical practice.Methods Evidence on management of ocular complications in intensive care patients ventilated in prone position was systemically retrieved in the guideline websites,professional association websites and databases,such as the BMJ Best Practice,UpToDate,Cochrane Library,Joanna Briggs Institute,PubMed,Web of Science,Science Direct,Embase,CNKI,Wanfang and other databases,including guidelines,clinical decisions,evidence summaries,expert consensuses,group standards,systematic reviews and scoping reviews,published from January 2013 to June 2023.The guidelines were individually evaluated by 4 researchers,and the remaining literature was individually evaluated by 2 researchers.The literature that met the criteria was extracted and graded.Results A total of 15 articles were involved,including 6 guidelines,2 clinical decisions,2 evidence summaries,3 systematic reviews,1 scoping review and 1 group standard.Finally,6 evidence topics and 16 pieces of best evidence were formed,including organization and training,risk identification,eye assessment,eye protection,position management and regular observation.Conclusion This study summarized the best evidence on the management of ocular complications in intensive care patients ventilated in prone position.In the application,the best evidence should be selected according to the clinical situation,so as to reduce the incidence of ocular complications and improve the quality of life of patients.

AIM To study the chemical constituents from the roots of Pfaffia glomerata(Spreng)Pedersen.METHODS The 95%and the 50%ethanol extract from P.glomerata were isolated and purified by silica gel,D101 macroporous resin,sephadex LH-20,polyamide,ODS,preparative HPLC and recrystallization,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1,2,4-benzenetriol(1),polypodine B(2),(-)-syringaresinol-4-O-β-D-glucopyranoside(3),poststerone(4),stachysterone B(5),calonysterone(6),taxisterone(7),makisterone C(8),20,22-O-(R-ethylidene)-20-hydroxyecdysone(9),20,22-O-(R-3-methoxycarbonyl)propylidene-20-hydroxyecdysone(10),shidasterone(11),5α-20-hydroxy-ecdysone(12),abutasterone(13),25-hydroxydacryhainansterone(14),methyl-α-D-fructofuranoside(15),methyl-β-D-fructofuranoside(16),chikusetsusaponin Ⅳamethyl ester(17),uridine(18).CONCLUSION Compounds 1-6,8-16,18 are isolated from P.glomerata for the first time,and compounds 1,3-6,8-16,18 are isolated from the genus of Pfaffia for the first time.

Objective:To investigate serum levels of retinol-binding protein 4(RBP4)and cystatin C(CysC)in pa-tients with coronary heart disease(CHD)and their association with intestinal flora.Methods:A total of 97 CHD patients admitted in our Department of Critical Care Medicine from December 2019 to December 2020 were treated as CHD group,another 99 healthy subjects undergoing physical examination simultaneously were regarded as control group.Serum levels of RBP4 and CysC,positive rates and number of intestinal flora were compared between two groups.With serum mean levels of RBP4 and CysC in CHD patients as critical value,they were divided into serum RBP4 high level group(RBP4≥35.97 ng/ml,n=53)and low level group(RBP4＜35.97 ng/ml,n=44),serum CysC high level group(CysC≥ 1.49 ng/ml,n=49)and low level group(CysC＜1.49 ng/ml,n=48).Number of intestinal flora were compared between different level subgroups,and Pearson method was used to analyze the asso-ciation of RBP4,CysC levels with flora number.Results:Compared with control group,there were significant rise in RBP4 and CysC levels,and significant reductions in culture positive rates and flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus(P＜0.001 all),and significant rise in culture positive rates and flora numbers of Staphylococcus and Escherichia coli in CHD group(P＜0.001 all).Compared with RBP4 low level group,there were significant reductions in flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus,and signifi-cant rise in flora numbers of Staphylococcus and Escherichia coli in RBP4 high level group(P＜0.001 all);com-pared with CysC low level group,there were significant reductions in flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus,and significant rise in flora numbers of Staphylococcus and Escherichia coli in CysC high level group(P＜0.001 all).Pearson correlation analysis indicated that RBP4 level was significant inversely correla-ted with flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus(r=-0.626～-0.482,P＜0.001 all),and significant positively correlated with flora numbers of Staphylococcus and Escherichia coli(r=0.302,0.337,P＜0.01 both);CysC level was significant inversely correlated with flora numbers of Bifidobacteri-um,Firmicutes,Lactobacillus and Proteus(r=-0.621～-0.502,P＜0.001 all),and significant positively corre-lated with flora numbers of Staphylococcus and Escherichia coli(r=0.308,0.340,P＜0.01 both).Conclusion:Se-rum levels of RBP4 and CysC increase in CHD patients,and they are closely related to the composition of intestinal flora.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.