ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg^-1）， and losartan capsules （10.29 mg·kg^-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L^-1）， high glucose （35 mmol·L^-1）， DMSO （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

The pachychoroid spectrum disorders (PSD) refers to a group of clinical disorders characterized by common features of pathological choroidal thickening and potential pathogenic mechanisms. The pathological mechanism of PSD is very complex, and the theory of venous overload provides valuable research directions. The multimodal imaging technology represented by optical coherence tomography angiography has continuously evolved to provide clear and three-dimensional images of the fundus, making it easier to diagnose and monitor PSD at an early stage. There is no unified consensus on how to develop a treatment plan for PSD, and current research has shown that feasible treatments include drug therapy, laser photocoagulation therapy, and photodynamic therapy. However, the evidence of effectiveness and safety provided by these studies is still not sufficient. Surgery and integrative Chinese and Western medicine may provide new prospects for the treatment of PSD. In the future, it is necessary to further develop reasonable research programs, expand the sample size, strengthen follow-up observation, and provide more safe and effective treatment programs for patients.

Objective:To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF).Methods:A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE ( n=1 127) and SE ( n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results:In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio ( OR)=2.75, 95% confidence interval ( CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L ( OR=2.07, 95% CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L ( OR=1.91, 95% CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% ( OR=2.45, 95% CI 1.63-3.69, P<0.01), left atrial diameter>40 mm ( OR=1.54, 95% CI 1.16-2.07, P=0.003), and CHA 2DS 2-VASc score≥3 ( OR=15.14, 95% CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE ( OR=0.28, 95% CI 0.15-0.51, P<0.01). Conclusions:History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA 2DS 2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

LC3-associated phagocytosis (LAP) is a special phagocytosis occurring at the intersection of the two pathways of phagocytosis and autophagy. A hallmark event of the LAP process is the recruitment of microtubule-associated proteinⅠlight chain type 3-Ⅱ(LC3Ⅱ) to the phagosome surface of the monolayer membrane structure. The LAP pathway relies on the functions of the RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein (Rubicon) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The LC3-associated phagosome (LAPosome) binds to the lysosome to digest and degrade the contents. In recent years, increasing studies have found that LAP plays an important role in the infections caused by pathogenic microorganisms including fungi and bacteria. LAP is a crucial way in the host to resist and degrade the infection of pathogenic microorganisms. However, some pathogenic microorganisms can effectively escape from LAP in the host and even use LAPosome as a place for colonization and replication. This article summarized the recent progress in the role of LAP in host defense against pathogenic microorganism infection and the significance of it in the occurrence and development of diseases.

Objective: To observe the clinical efficacy of umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang prescription of different dosages in treating damp-heat diarrhea in young children. Methods: Seventy-two kids with diarrhea of damp-heat pattern were recruited and divided into a high-dosage group and a low-dosage group using the random number table method, with 36 cases in each group. They all received conventional antidiarrheal treatment and umbilical application with herbal cakes. However, the herbal cakes for the high-dosage group were made of the mixture of Ge Gen Qin Lian Tang powder and water, and those for the low-dosage group consisted of 10％ Ge Gen Qin Lian Tang powder and 90％ auxiliary materials (corn starch) plus water. The treatment duration was 3 d. The clinical efficacy, antidiarrheal rate, effective rate for symptoms and signs of traditional Chinese medicine (TCM), TCM symptoms score, and safety indicators were compared between the two groups. Results: After the treatment, the TCM symptoms scores dropped significantly in both groups (P<0.01) and were lower in the high-dosage group than in the low-dosage group (P<0.05). The clinical efficacy was more significant in the high-dosage group than in the low-dosage group after the treatment, and the between-group difference was statistically significant (P<0.05); the antidiarrheal rate was markedly higher in the high-dosage group than in the low-dosage group (P<0.05). Regarding the TCM symptoms and signs, the high-dosage group showed better results in improving the greasy and yellowish tongue coating, bowel movement frequency, watery excrement, short and dark urine, red tongue body, red anus, vomiting, bowel sounds, and abdominal bloating compared with the low-dosage group, and the between-group differences were statistically significant (P<0.01). Conclusion: Umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang is safe, reliable, and effective in treating damp-heat diarrhea in young children; the high-dosage herbal cakes produce more significant efficacy than the low-dosage ones and are worth further investigation.

Objective:To observe and investigate the effect of HIF-2α in the process of neovascularization of proliferative diabetic retinopathy (PDR).Methods:Retrospective clinical study. From July 2014 to July 2015, 60 eyes of 57 PDR patients diagnosed in Ophthalmology Department of Affiliated Hospital of Qingdao University were included in the study. Twenty-eight eyes of 27 patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml) at 2-7 days before surgery (ranibizumab group) and other 32 eyes of 30 patients did not (group without ranibizumab). Eighteen eyes of 18 patients with epiretinal membranes were included as controls. Pathological specimens of PDR fibrovascular membrane and premacular membrane were obtained during vitrectomy. The immunohistochemical staining and real-time PCR (RT-PCR) were used to detecting the expression of HIF-2α, Dll4 and VEGF. Kruskal-wallis test was used to compare the expression differences of correlation factors between groups. Spearman correlation analysis was used to analyze the relationship between the two variables.Results:The immunohistochemical staining revealed that there were positive expression of HIF-2α, Dll4 and VEGF in all PDR membranes, regardless of the injection of the ranibizumab. The levels of HIF-2α, Dll4 and VEGF protein in the group without ranibizumab were higher than those of the ranibizumab group ( t=4.36, 6.01, 4.82; P=0.000, 0.008, 0.016). RT-PCR showed that the differences of the mRNA expression of HIF-2α, Dll4 and VEGF were all statistically significant among the PDR patients and controls ( H=18.81,19.60, 20.50; P=0.000, 0.000, 0.000). The expression of HIF-2α, Dll4 and VEGF in the PDR membranes was higher than that of epiretinal membranes from non-diabetic patients. In the PDR patients,the expression of HIF-2α, Dll4 and VEGF of the group without ranibizumab was higher than that of the ranibizumab group. The spearman correlation analysis showed that the expression of mRNA between HIF-2α and Dll4, HIF-2α and VEGF were both significantly correlated ( r=0.95, 0.87; P<0.05). Conclusions:The expression of HIF-2α in the PDR membranes was higher than that of the controls. It is positively correlated with the expression of the DLL4 and VEGF.

Objective To observe the effect of Delta-like ligand 4 (Dll-4) on the pathological structure of retina in early diabetic rats (DM) and its relationship with vascular endothelial growth receptor-2 (VEGFR-2).Methods A total of 70 male Sprague-Dawley rats were randomly divided into normal group and DM group,with 10 and 60 rats in each group,respectively.The rats of DM group was induced by intraperitoneal injection of streptozotocin to established DM model.The rats with blood glucose recovery and death were excluded,and the final 60 rats were included in the statistics.Rats in the normal group were injected with an equal volume of citric acid-sodium citrate buffer.Rats in the DM group were divided into DM 1 month (DM lm) group,DM 2 months (DM 2m) group,DM 3 months (DM 3m) group and DM 3m + Anti group,DM 3m + phosphate buffer solution (PBS) group by random number table method,and 10 rats in each group.In the DM 3m+Anti group,4 μl ofantiDll-4 polyclonal antibody was injected into the vitreous cavity,and the antibody concentration was 0.25 mg/ml.The DM 3m+PBS group was intravitreally injected with an equal volume of PBS.Five days after the injection,the rats were sacrificed.Rats in the DM 3m group and the normal group were not treated,and were sacrificed 3 months after the model was established.The structure and microvascular changes of the retina were observed by hematoxylin-eosin staining,and the total thickness of the retina was measured.The expression of Dll-4 and VEGFR-2 in the retina was detected by immunohistochemistry and fluorescence quantitative polymerase chain reaction (PCR).One-way analysis of variance was used to compare the expression of Dll-4 and VEGFR-2 in the retina of each group.The least significant difference t test was used to compare the two groups.Results Light microscopy showed that the retinal ganglion cells layer in the DM 3m group were obviously edematous,the inner and outer nuclear layers were thinner,the number of cells was reduced,the arrangement was disordered,the edema of outer plexiform layer was obvious,and the microvessels were abnormally dilated.In the DM 3m+Anti group,the edema of outer plexiform layer was lessened than that of the DM 3m group,and the other layers were not significantly different from the DM 3m group.Compared with the normal group,the total retinal thickness of the DM 3m group,the DM 3m+Anti group and the DM 3m+PBS group increased (t=5.596,3.290,4.286;P=0.000,0.008,0.002).Immunohistochemical staining showed that a small amount of Dl14 was positively expressed in the retinal ganglion cell layer of the normal group;a small amount of VEGFR-2 was positively expressed in the ganglion cell layer and the inner and outer nuclear layers.The positive expression of Dll-4 and VEGFR-2 in retinal vascular endothelial cells of DM 3m group increased significantly.The expression of Dll-4 was significantly decreased in the retinal layers and vascular endothelial cells ofDM 3m+Anti group,while the expression of VEGFR-2 was significantly increased.There was no significant difference between the positive expression of Dll4 and VEGFR-2 in the DM 3m+PBS group and the DM 3m group.The results of real-time PCR showed that the relative expression of Dll-4 and VEGFR-2 mRNA in the DM 3m group was significantly higher than that in the normal group (t=6.705,20.871;P＜0.05).Compared with DM 3m group,the relative expression of Dll-4 mRNA in DM 3m+Anti group decreased,and the relative expression of VEGFR-2 mRNA increased (t=2.681,3.639;P＜0.05).The relative expressions of Dll-4 and VEGFR-2 mRNA in the DM 3m+PBS group and DM 3m group were not statistically significant (t=0.513,0.657;P＜0.05).Conclusions The expression of Dll-4 in retinal vascular endothelial cells is gradually increased during the early retinopathy of DM rats.The expression of Dll-4 is inhibited,the expression of VEGFR-2 is up-regulated,and the plexus edema is alleviated.

Objective To explore the relationship between the expression of HBx protein in HBV-related HCC samples and the clinical implications.Methods Elivision two-step was used in this study to detect the expression level of HBx protein in 40 HCC tissues,corresponding para-tumorous tissues from patients with HBV-related HCC undergoing curative hepatectomy.The relationship between HBx protein and clinical parameters (such as gender,age,TNM stage,HBV-DNA load,AFP,liver cirrhosis,a merger of vascular invasion,tumor infiltrating lymphocytes,Edmondson-Steiner histopathological grading,with or without relapse within 24 months) were analyzed.Results (1) The expression of HBx protein in the tumorous tissues was significantly lower than that of para-tumorous tissues (P ＜ 0.05).(2) In the tissues of para-tumorous,the expression of HBx protein in group HBV-DNA ＜ 500 IU/ml was significantly lower than that of group HBV-DNA≥500 IU/ml (P ＜0.05).There were no significant differences in the expression of HBx protein irrespective of gender,age,cirrhosis and the AFP level.(3) In the tissues of tumorous,the expression of HBx protein in group with vascular invasion was significantly higher than that of group without vascular invasion (P ＜ 0.05).However,there were no significant differences in the expression of HBx protein among the factors of TNM stage and Edmondson-Steiner histopathology grading.(4) In para-tumorous tissues,the expression of HBx protein in group of lymphocytic infiltration was significantly higher than that without lymphocytic infiltration (P ＜ 0.05).In the tissues of tumorous,the expression of HBx protein in disease-free survival (DFS) ＜ 24M patients was significantly higher than DFS ≥ 24M (P ＜ 0.05).Conclusions High HBx expression in tumor tissues indicates poor prognosis while that in para-tumorous tissues predicts a better prognosis.

OBJECTIVE To explore the expression of Maspin in invasive fungal rhinosinusitis (IFRS) and the value of Maspin in the diagnosis of IFRS. METHODS Forty two cases of fungal rhinosinusitis (FRS) were set as the experimental group, which included 12 cases of IFRS and 30 cases of noninvasive fungal rhino-sinusitis (NIFRS). At the same time, 30 cases of chronic rhino-sinusitis were set as control group. Immunohistochemistry (IHC) was used to detect the expression of Maspin. RESULTS Compared with the control group, the expression of Maspin in FRS group decreased statistically (t=-3.367, P<0.05). The IFRS group, compared with other two groups, had the lowest expression of Maspin (t=-3.390, P<0.05; t=-4.143, P<0.05). By using Maspin score of 5.70 as the cut-off point, the sensitivity and specificity for the diagnosis of IFRS was 91.7% and 88.3% respectively. CONCLUSION The expression of Maspin is very low in IFRS group. Down-regulation of Maspin expression may be a potential indicator for diagnosis of IFRS.