ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

Kidney deficiency syndrome is a common clinical syndrome in traditional Chinese medicine （TCM）. With the progress of science and technology， clinical and animal experiments on kidney deficiency syndrome have made remarkable progress. Research on kidney deficiency and the nature of "kidney" involves a large number of physiological and pathological bases， which are closely related to physiological and pathological links in the human body， among which the neuroendocrine-immune network shares the closest relationship. However， there are still many challenges in modern research on kidney deficiency syndrome， such as expert consensus on clinical diagnostic criteria and evaluation indexes and optimization of animal experimental models. In the past decade， a large number of clinical and animal experiments have been reported in the literature on kidney deficiency syndrome， among which the literature focusing on the combination of disease and syndrome is predominant， and most of them focus on kidney Yang deficiency and kidney Yin deficiency， involving the exploration of many pathological mechanisms. Research on the mechanisms related to kidney deficiency syndrome encompasses multiple signaling pathways and various biochemical indicators， including the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-erythroid 2-relatedfactor-2（PI3K/Akt/Nrf2） signaling pathway， the Toll-like receptor 4/myeloid differentiation factor88/nuclear factor-κB（TLR4/MyD88/NF-κB） signaling pathway， the Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway， Osteoprotectin/nuclear factor-κB receptor activator ligand/receptor activator of nuclear factor-κB （OPG/RANKL/RANK） signaling pathway. The biochemical indicators cover the cyclic adenosine monophosphate/cyclic guanosine monophosphate （cAMP/cGMP） ratio， Na⁺-K⁺-ATPase activity， Ca²⁺-Mg²⁺-ATPase activity， adrenocorticotropic hormone （ACTH）， polycorticosterone （CORT）， 17-OHCS， and other sex hormone indicators， providing crucial reference values for diagnosing kidney Yang deficiency or kidney Yin deficiency. The literature related to kidney deficiency syndrome over the past decade was collated and excavated， with a view to providing a reference for research on kidney deficiency syndrome.

Objective To isolate endophytic fungi from Angelica sinensis and evaluate the bioactivity of their secondary metabolites.Methods Angelica sinensis and rhizosphere soil were utilized as materials.The tissue homogenization method was employed with six diverse culture media to isolate endophytic fungi.The antibacterial activity of secondary metabolites was gauged using a 96-well plate assay,while UV spectrophotometry was used to evaluate the inhibitory activity of four enzymes.Results A total of 153 fungal strains were isolated and purified from Angelica sinensis roots,stems,leaves,and soil.The samples exhibited specific inhibitory activities against adenosine deaminase(ADA),β-lactamase,xanthine oxidase(XO),and tyrosinase(TYR),with rates of 45.83%,52.78%,51.39%and 55.56%,respectively.Furthermore,1.39%of the samples displayed wide-ranging inhibitory effects against four indicator bacteria.Strain 6B also showcased the lowest inhibitory concentration values of 62.5 and 7.81 μg/mL against Escherichia coli ATCC25922 and ATCC35218,respectively,signifying its potential research significance.Conclusion Angelica sinensis has abundant endophytic fungal resources and is a good source for discovering active compounds,demonstrating certain research value.

Intracranial atherosclerotic stenosis (ICAS) is closely associated with cognitive impairment and dementia. This article reviews the manifestations, mechanisms, and interventions of cognitive impairment in patients with ICAS, aiming at increasing attention to ICAS, early identification and intervention, and delaying the occurrence and deterioration of cognitive impairment.

Objective To study the proteomic profiling of lung and colon during lung injury induced by lipopolysaccharide(LPS).Methods Mice were divided into four groups:the control,LPS,LPS+ Platycodonis Radix(PR)and LPS+ Rhei Radix et Rhizoma(RRR).LPS was injected into the lungs through trachea,and the drugs were given by intragastric injection.The mice were weighed,the faeces of each mouse were determined,and the lungs and colon were isolated for analysis of pathophysiological changes and proteomics.Results ①After 7 days of LPS,the weight of mice decreased,the lung showed inflammatory changes,and the faeces increased.Both PR and RRR can improve the inflammation.②There are lot of proteins was increased in lung mainly involved in gene transcription and in colon mainly involved in mitochondrial,endoplasmic reticulum and metabolism,etc.The up-regulated proteins shared by both lung and colon were involved in myoprotein contraction.PR can inhibit the up-regulated protein more than RRR in lung.③There are large number of proteins were down-regulated in lung involved in cell membrane and in colon involved in nucleic acid binding and ATP binding.The down-regulated proteins shared by both lung and colon were involved in endoplasmic reticulum,nucleic acid binding and cell membrane,etc.The down-regulated proteins in lung by PR are more than those by RRR,which is involved in endoplasmic reticulum,cell membrane,etc.Conclusion LPS-induced lung injury can cause changes in the expression of protein in lung and colon proteins,and the increase in the expression of myoprotein contraction genes may be one of the molecular mechanisms related to lung and colon.

AIM: To explore the effect of spinal anesthesia on ventricular arrhythmia and involved mechanisms in myocardial ischemia-reperfusion (MIR) rats. METHODS: The rat MIR model was made by occlusion the left anterior descending coronary artery for 30 minutes and reperfusion for 45 minutes. Bupivacaine (0.05 mL / 100 g, 1 mg / kg) was injected slowly via intrathecal for spinal anesthesia. The electromyelogram at T2 thoracic spinal cord was recorded. Ventricular arrhythmias, cardiac function, myocardial damage were assessed by electrocardiography, echocardiography and TTC or HE staining. RESULTS: MIR reduced left ventricular short-axis shortening (LVFS) and left ventricular ejection fraction (LVEF), caused myocardial histological damage and ventricular arrhythmias, promoted spinal electrical discharge frequency and amplitude in T2 dorsal horn. Spinal injection of bupivacaine could significantly reduce spinal cord electrical activities and eliminate MIR-induced arrhythmias. Moreover, bupivacaine also significantly improved MIR-induced myocardial histological damage and cardiac function inhibition. CONCLUSION: Spinal anesthesia can reduce ventricular arrhythmias induced by MIR. The mechanism may be related to the effect of abolishing spinal nerve excitability.

OBJECTIVE To es tablish the fingerprints of pith-nodecayed and pith-decayed Scutellaria baicalensis ，and to investigate the difference of their anti-inflammatory activities. METHODS HPLC method was adopted to establish the fingerprints of 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis . SIMCA 14.1 software was adopted to screen the markers of weight difference between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis ，using variable importance in projection （VIP）＞1 as standard. Using the inhibitory rates of NO ，IL-6 and IL- 1β in supernatant of lipopo- lysaccharide（LPS）-induced monocyte macrophages （RAW264.7 cells）as indexes ，the anti-inflammatory activities of pith-decayed and pith-nodecayed S. baicalensis were evaluated and median effective concentration （EC50）of NO were calculated. The gray correlation method was used for spectrum-effect relationship analysis ；SPSS 26.0 software was used for cluster analysis using the inhibitory rates of NO ，IL-6 and IL- 1β in cells at the concentration of 50 μg/mL. RESULTS There were 15 common peaks in 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis ，and the similarity of them was greater than 0.990. There were total of 8 peaks with VIP 1.0，they were peak 14，12，15，6，10，13，11 and 4. At jcqinge@163.com the concentration of 50 μg/mL，the inhibitory rates of pith- decayed S. baicalensis extract to NO ，IL-6，IL-1 β and the average EC 50 were 62.14％-71.13％，3.32％ -18.38％ and 93.12％-95.47％ and 25.35 μg/mL，respectively；those of pith-nodecayed S. baicalensis extract were 39.52％-50.19％， 6.21％-22.55％，94.10％-96.44％ and 58.63 μg/mL，respectively. Average NO inhibition rate of pith-decayed S. baicalensis extract was significantly higher than that of pith- nodecayed S. baicalensis extract；average EC 50 and average IL- 6 inhibitory rate of pith-decayed S. baicalensis extract were significantly lower than those of pith-nodecayed S. baicalensis extract（P＜0.05）. There was no statistical significance in average inhibitory rate of IL- 1β（P＞0.05）. The correlation degrees of peaks 2-3，5-8 and 10-11 with inhibitory rate of NO were all greater than 0.8. The correlation degrees of peaks 2，5，8-9 with inhibitory rate of IL- 1β were all greater than 0.9. The correlation degrees of 15 common peaks with inhibitory rate of IL- 6 were all less than 0.8. Ten batches of samples could be grouped into two categories ，K1-K5 were clustered into one category and T 12-T16 were clustered into one category. CONCLUSIONS At the concentration of 50 µg/mL，the inhibitory effect of pith-decayed S. baicalensis extract to NO is stronger than that of pith-nodecayed S. baicalensis extract，while the inhibitory effect on IL- 6 is weaker than that of pith-nodecayed S. baicalensis extract；they have similar inhibitory effect on IL- 1β. The corresponding components of peak 6，10-11 are preliminarily identified as main chemical components of the difference in anti-inflammatory activity between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis .

Objective     To analyze the perioperative outcomes of uniportal thoracoscopic lobectomy compared with three-port thoracoscopic lobectomy. Methods     Data were extracted from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University. Perioperative outcomes of the patients who underwent uniportal or three-port thoracoscopic lobectomy for lung cancer during January 2014 through April 2021 were analyzed by using propensity score matching. Altogether 5 817 lung cancer patients were enrolled who underwent thoracoscopic lobectomy (uniportal: 530 patients; three-port: 5 287 patients). After matching, 529 patients of uniportal and 1 583 patients of three-port were included. There were 529 patients with 320 males and 209 females at median age of 58 (51, 65) years in the uniportal group and 1 583 patients with 915 males and 668 females at median age of 58 (51, 65) years in the three-port group. Results     Uniportal thoracoscopic lobectomy was associated with less intraoperative blood loss (20 mL vs. 30 mL, P<0.001), longer operative time (115 min vs. 105 min, P<0.001) than three-port thoracoscopic lobectomy. No significant difference was found between the two groups regarding the number of lymph node dissected, rate of conversion to thoracotomy, incidence of postoperative complication, postoperative pain score within 3 postoperative days, length of hospital stay, or hospitalization expenses. Conclusion     Uniportal video-assisted thoracoscopic lobectomy is safe and effective, and the overall perioperative outcomes are comparable between uniportal and three-port strategies, although the two groups show differences in intraoperative blood loss.

Objective:To evaluate the effect of uncoupling protein 1 (UCP1) expression of perirenal fat on the prognosis of clear cell renal cell carcinoma (ccRCC) .Methods:From Feb. 2013 to Oct. 2013 and Mar. 2015 to Oct. 2015, 98 patients with ccRCC who underwent retroperitoneal laparoscopic radical nephrectomy were analyzed. UCP1 mRNA of perirenal fat around tumor was detected by RT-qPCR. Preoperative Computed tomography (CT) images were used to evaluate the thickness and adhesiveness of perirenal fat. According to the UCP1 mRNA value, the patients were divided into high UCP1 group (42 cases) and low UCP1 group (56 cases) . The general clinical data, perirenal fat thickness and adhesiveness were compared, and Kaplan Meier curve was used to evaluate the difference of progression free survival (PFS) between the two groups. Univariate and multivariate Cox analysis were used to determine the potential independent prognostic factors of PFS.Results:In the high UCP1 group, the renal fat thickness, the ratio of fat adhesion, the ratio of Ⅲ to Ⅳ in Fuhrman grade and the ratio of >T2 in T stage were higher than those in the low UCP1 group[ (13.84±2.41) vs (10.75±1.99) , 42.86% vs 16.07%, 28.57% vs 8.93%, 21.43% vs. 5.36%; P=0.000, P=0.003, P=0.011, P= 0.037]. During the follow-up period (median, 62.0 months) , 15 cases (12 cases of high UCP1 group, 3 case of low UCP1 group) developed tumor progression. Kaplan Meier curve showed that PFS of high UCP1 group was worse than that of low UCP1 group (71.43% vs 94.64%, P=0.001) . Cox regression analysis showed that high UCP1 expression and high T stage were significantly correlated with low PFS ( β=1.334, RR=3.796, 95% CI=1.009-14.280, P= 0.048; β=2.886, RR=17.930, 95% CI=5.538-58.047, P=0.000) . Conclusions:The increased UCP1 expression of perirenal fat may be an independent risk factor of tumor progression in ccRCC. Combined with the assessment of browning of perirenal adipose tissue may be helpful for risk stratification of ccRCC patients after surgery.

The Notch signaling pathway plays an important role in cell fate and homeostasis.Various studies have proved that the Notch signaling pathway has strong effects on corneal wound healing and the maintenance of corneal homeostasis.Limbal stem cells inhibit differentiation and proliferation by inhibiting the Notch signaling pathway.Physiologic downregulation promotes cell migration and wound coverage in the early stage of corneal epithelial repair, and physiologic upregulation in the late stage of corneal epithelial repair is related to preventing excessive stratification of corneal epithelial cells and maintaining cell differentiation.Fibrosis is correlated with Notch after corneal stromal injury.The Notch signaling pathway is directly involved in the endothelial-to-mesenchymal transition induced by transforming growth factor-β after corneal endothelial injury.In addition, there are interactions between the Notch signaling pathway and 14-3-3 sigma, epidermal growth factor receptor, Sirt6, microRNA, and matrix metalloproteinases in maintaining corneal epithelial homeostasis, corneal epithelial differentiation, corneal stromal excessive inflammatory response, corneal neovascularization, etc.This review summarizes the function of the Notch signaling pathway in corneal wound healing.