Objective To investigate the efficacy of Lishui Xiaozhong Granules combined with Conbercept for the treatment of diabetic macular edema(DME).Methods From December 2022 to June 2023,46 patients(46 eyes)with DME of spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome admitted to Foshan Hospital of Traditional Chinese Medicine were selected as the study objects.According to the principle of single-blind randomized controlled trial,the patients were randomly divided into treatment group and control group by random number table method,with 23 cases(23 eyes)in each group.The control group was treated with intravitreal injection of Conbercept,and the treatment group was treated with oral use of Lishui Xiaozhong Granules on the basis of treatment for the control group.The course of treatment lasted 3 months and then a follow-up for 6 months was conducted.Before and after treatment,the two groups were observed int the changes of traditional Chinese medicine(TCM)syndrome score,best corrected visual acuity(BCVA,LogMAR),central macular thickness(CMT),mean vessel density(VD)of superficial capillary plexus(SCP)and deep capillary plexus(DCP)in macular area,and the amplitude density and the latency of P1 and N1 wave in the R1 ring of multifocal electroretinogram(mf-ERG).Results(1)After 1,3 and 6 month(s)of treatment,BVCA in the two groups was improved when compared with that at the previous observation time point(P＜0.05),and the improvement in the treatment group was superior to that in the control group after 1,3 and 6 month(s)of treatment(P＜0.01).(2)After 1,3 and 6 month(s)of treatment,the CMT of the two groups was lowered as compared with that at the previous observation time point(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After 6 months of treatment,SCP-VD and DCP-VD in the two groups showed no obvious changes when compared with those before treatment(P＞0.05),the differences between the two groups after treatment were no statistically significant,either(P＞0.05).(4)After 1,3 and 6 month(s)of treatment,the amplitude densities of P1 wave and N1 wave in the R1 ring of mf-ERG in the two groups were increased when compared with those at the previous observation time point(P＜0.05),and the latency of P1 wave and N1 wave was shortened when compared with that at the previous observation time point(P＜0.05),and the treatment group had stronger effect on increasing the amplitude densities and on shortening the latency than the control group(P＜0.01).(5)After 6 months of treatment,the scores of TCM syndromes in the treatment group were lowered(P＜0.05)while the scores in the control group showed no obvious changes as compared with those before treatment.The intergroup comparison showed that the decrease of TCM syndrome score in the treatment group was significantly superior to that in the control group(P＜0.01).Conclusion In the treatment of DME with spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome,Lishui Xiaozhong Granules combined with Conbercept have no influence on improving the SCP-VD and DCP-VD,but the combined therapy exerts satisfactory efficacy on increasing BCVA and on improving macular oedema,retinal function in the macular area and systemic symptoms.

AIM:To explore the impact of sphingosine 1-phosphate receptor 5(S1PR5)on lipopolysaccha-ride(LPS)-induced neuroinflammation and cognitive-behavioral impairments in mice,alongside the anti-inflammatory im-pacts on BV2 cells and associated mechanisms.METHODS:(1)C57BL/6 wild-type(WT)mice and homozygous S1PR5 knockout(KO)mice were utilized and categorized into WT control,WT-LPS,S1PR5 KO control,and S1PR5 KO-LPS groups using the random number method.Neuroinflammatory models in mice were induced by a single intraperitoneal injection of 5 mg/kg LPS in the WT-LPS and S1PR5 KO-LPS groups,while an equivalent volume of saline was injected in-to the WT control and S1PR5 KO control groups.Following 7 days of modeling,the Morris water maze test was conducted,followed by the collection of brain tissues from each group of mice.Hippocampal tissue sections were stained with Nissl.The mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in hippocampal tis-sues were determined using RT-qPCR.Western blot and tissue immunofluorescence techniques were employed to assess the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in hippocampal tissues.(2)The BV2 cells underwent LPS stimulation to induce an inflammatory response and were treated with either the S1PR5 ago-nist A971432 or lentiviral overexpression of S1PR5.The effects of S1PR5 agonism or overexpression on S1PR5,IL-1β,IL-6,TNF-α,and CD206 were assessed using RT-qPCR.Additionally,CD206 expression was examined via cellular im-munofluorescence.Western blot was employed to analyze the protein levels of microglia polarization markers CD206,in-ducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX2),and NLRP3,as well as p-NF-κB,cleaved caspase-1,and IκBα.RESULTS:(1)Findings from in vivo experiments indicated that S1PR5 KO notably exacerbated LPS-induced memory impairments in mice,alongside increased mRNA levels of IL-1β and IL-6,and increased protein levels of NLRP3 in the hippocampus.(2)The presence of S1PR5 in BV2 cells remained unaffected by variations in A971432 concentration and exposure duration.(3)Activation of S1PR5 or its overexpression significantly mitigated LPS-induced expression of IL-1β,IL-6,and TNF-α,while concurrently enhancing CD206 expression in BV2 cells at the mRNA level.At the protein level,it led to a noteworthy increase in CD206 expression,indicative of M2-type macrophages,and a reduction in the ex-pression of iNOS and COX2,markers of M1-type macrophages.Furthermore,it downregulated NLRP3,p-NF-κB,and cleaved caspase-1 expression,while upregulating IκBα expression.CONCLUSION:S1PR5 deficiency exacerbates cog-nitive deficits in mice by promoting neuroinflammatory responses induced by LPS.

Objective To investigate the effect of sodium houttuyfonate on the expression of PI3K and AKT1 and mTOR mRNA in the lung of rats with chronic obstructive pulmonary disease(COPD),and reveal the possible mechanism of the COPD treated with sodium houttuyfonate. Methods Twenty-four male Wistar rats were randomly divided into normal control group,model control group,dexamethasone group and sodium houttuyfonate group(n=6 for each). The rat models of COPD were established by intratracheal instillation of lipopolysaccharide and smudging. The expressions of PI3K and AKT1 and mTOR mRNA were determined by real-time PCR. The morphological changes of the lung tissue was examined by histopathology. Results Compared with the normal control group,the expressions of PI3K and AKT1 were significantly in-creased and mTOR mRNA was significantly decreased in the model group(P<0.01,P<0.05). Compared with the mod-el group,the expressions of PI3K and AKT1 were significantly decreased and mTOR mRNA was significantly increased in the sodium houttuyfonate group and dexamethasone group(P<0.01,P<0.05). Compared with the dexamethasone group, the expression of mTOR mRNA was significantly increased in the sodium houttuyfonate group(P<0.05). The pathological observation indicated that there were local pulmonary consolidation and a extensive neutrophil infiltration in the alveolar cav-ity. Prominent pulmonary interstitial fibrous hyperplasia was observed in the model group. The pathological manifestations were much ameliorated than those of the model group,and only mild interstitial pneumonia and a slight fibrous hyperplasia were seen in the sodium houttuyfonate and the dexamethasone groups. Conclusions Sodium houttuyfonate reduces the in-jury of lung tissue and has protective effect on COPD rats. The mechanism is probably related to the down-regulatation of expression of PI3K and AKT1 mRNA and up-regulatation of expression of mTOR mRNA in COPD rats.

Objective To investigate the relationship between abnormal metabolism of aggrecan and joint destruction in patients with rheumatoid arthritis (RA).Methods 140 RA patients with duration less than 24 months were enrolled into this study.The study also included 100 normal controls and 95 patients with other rheumatic diseases.Three monoclonal antibodies (5D4,7D4 and BC-3) of aggrecan were used to detected aggrecan catabolic fragments in serum of RA patients and the other two groups of controls by enzyme linked immunosorbent assay (ELISA),and the correlation of aggrecan catabolic fragments with joint damage were analyzed.Sharp evaluation of hand joints in RA patients were performed at baseline and after one year follow-up.Calculating the area under the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of aggrecan catabolic fragments detected in serum of RA patients.Results Both levels of 5D4 fragment and BC-3 fragment of RA group were higher than those of normal control [5D4 of RA:(5.8±2.1) ng/μl,normal control:(2.2±1.3) ng/μl;BC-3 of RA:(11.1±3.4) ng/μl,normal control:(5.0±2.1) ng/μl,F=38.65,24.07,P＜0.001).There was no difference in 7D4 fragment among three groups (F=0.589,P=0.478).Both two fragment levels of RA patients with anti-CCP positive were greater than those patients with anti-CCP negative [5D4:(5.6±1.3) ng/μl vs (4.4±1.1) ng/μl,F=21.23,P＜0.01;BC-3:(12.2±3.9) ng/μl vs (9.3±2.8) ng/μ1,F=27.14,P＜0.01].Linear Regression showed that serum fragments detected by 5D4 and BC-3,and anti-CCP positive were risk factors for Sharp deterioration after one year follow-up.The sensitivity and specificity of combined detection of two aggrecan fragments in serum of RA patients for the prediction of joint Sharp were 56.5％ and 84.2％ respectively.Positive predictive value and negative predictive value are 74.3％ and 70.6％.respectively.Application of areas of ROC to identify the best evaluation of Sharp was 0.798.Conclusion There is positive correlation between aggrecan catabolic fragments in serum and joint Sharp evaluation of RA patients.Detection of aggrecan catabolic fragments in RA patients may predict early joint destruction.

Objective To investigate the effects of Xuanfeitongfufang Decoction on expressions of MD-2, NF-κB protein and its mRNA in lung of the rats with acute lung injury caused by LPS. Methods Wistar rats were randomly divided into normal group, model group, dexamethasone group and Xuanfeitongfufang Decoction large-, medium-, small-dose group, each group had eight rats. The ALI rat model was established by LPS tail-intravenous injection (6 mg/kg). The rats in Xuanfeitongfufang Decoction groups were pretreated by Xuanfeitongfufang Decoction (15.12, 7.56, 3.78 g/kg) for 3 days before LPS induced ALI. The rats in dexamethasone group were pretreated by dexamethasone (5 mg/kg). MD-2, NF-κB protein and its mRNA were measured by immunohistochemistry and PCR. The histopathology of the lung injury was observed by light microscope. Results Compared with normal group, the expression of MD-2, NF-κB protein and its mRNA were obviously increased in model group (P<0.01). Compared with model group, the expression of MD-2, NF-κB protein and its mRNA were obviously decreased in Xuanfeitongfufang Decoction groups and dexamethasone group (P<0.01), and there was no obvious difference between Xuanfeitongfufang Decoction groups and dexamethasone group. Light microscope observation indicates that there were large areas of pulmonary hemorrhage and necrosis in model group. While in Xuanfeitongfufang Decoction group and dexamethasone group, the pathological manifestations were much more ameliorated than those of the model group. The lung bronchiale inflammation appeared occasionally, and the edema was lightly. Conclusion Xuanfeitongfufang Decoction can lessen the injury of lung tissue and has protective effects on rats with ALI, the mechanism is possibly related to the inhibition of the expressions of MD-2 and NF-κB protein and its mRNA in injured lung tissues.

Some Bemorheogical indexes of the middle-aged persom and the ages of "mental work pattem" health state were compared with that of the middle aged persen and the aged in general health in the paper, The authors found the values of the former were higher than that of the latter in varied degrees. Except the both sexes hematocrit and the male's erythrocyte sedimentation rate, the other inedxes of the both groups showed very significant differences. According to the cpidemiological data which showed the incidences of ischemic cardio-cerebrovascular diseases in the mental works were higher than that in the physical labourers, it is suggested that the differences of hemorheological characterislics in the both may be the one of the causes. The authors suggest that it should pay atterntion to health states of the middle aged person and the aged who had elementary normal conclusion in physical examination but they had abnormal high values of one or some hemorheological indexes.