ObjectiveTaking the oligosaccharides in Rehmanniae Radix（RR） as the research object， the content determination method based on high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） and thin layer chromatography（TLC） identification method were established to explore the content and distribution of oligosaccharides in different RR herbs and decoction pieces. MethodA total of 10 batches of fresh and raw RR， 12 batches of RR decoction pieces and Rehmanniae Radix Praeparata（RRP） were collected. A TLC identification method for fructose， sucrose， manninotriose， raffinose and stachyose in RR was established by using silica gel G thin-layer plates with ethyl acetate-water-anhydrous formic acid-glacial acetic acid（12∶6∶5∶4） as the developing agent and 10% sulfuric acid-ethanol solution as chromogenic agent. A HPLC-ELSD was used to determine the contents of fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose in different RR herbs and decoction pieces. Then principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to analyze the contents of 7 kinds of saccharides in RR herbs and decoction pieces， and the differential components were screened with the value of variable importance in the projection（VIP）>1. ResultThe results of TLC identification showed that fresh RR， raw RR and its decoction pieces showed spots of the same color on the corresponding positions with the control products of stachyose， raffinose and sucrose， while the TLC of RRP showed spots of the same color at corresponding positions to manninotriose and fructose controls. The results of methodological investigations of 7 analytes met the requirements of determination. Only glucose， sucrose， raffinose and stachyose were detected in 10 batches of fresh RR and 10 batches of raw RR herbs， the average contents of which were 0.84%， 4.62%， 2.42% and 57.90% in fresh samples， while those were 3.16%， 9.36%， 7.05% and 38.10% in raw samples， respectively. In 12 batches of RR decoction pieces， the contents of the above seven sugars（fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose） were 1.68%， 4.27%， 9.96%， 0.53%， 6.85%， 3.05% and 37.52%， respectively. In 12 batches of RRP， the contents of the above seven sugars were 10.62%， 11.01%， 1.25%， 3.35%， 1.12%， 28.16% and 6.39%， respectively. The results of multivariate statistical analysis showed that fresh RR， raw RR and RRP could be distinguished from each other by the contents of the 7 sugars， and the main differential components were stachyose， sucrose， raffinose and manninotriose. ConclusionIn terms of oligosaccharides， the contents and types of saccharides in different herbs and decoction pieces of RR are quite different， and the TLC identification method based on this can be used to distinguish raw RR from RRP， which can lay a foundation for improving the quality standard of RR and developing and applying oligosaccharides in different processed products of RR.

Objective To explore the key molecular targets and possible mechanisms of Aidi injection in the treatment of ovarian cancer using network pharmacology and cell experiments.Methods TCMSP database was used to screen the active ingredients and tar-gets of Aidi injection,and the abnormal expressed genes of ovarian cancer were screened,and the possible targets of Aidi injection in o-varian cancer were obtained after intersection analysis.Then,protein-protein interaction analysis,drug-compact-target network con-struction and enrichment analysis of possible targets were performed.The target was further screened,and the key genes related to the prognosis of ovarian cancer were experimentally verified.After treated with 50mg/ml Aidi injection,the cell proliferation ability was ob-served by CCK-8 assay,and the expression of core target genes was detected by real-time quantitative polymerase chain reaction.Results A total of 13 possible targets of Aidi injection in ovarian cancer were screened.These targets were mainly enriched in signaling pathways closely related to the occurrence and development of tumors,such as apoptosis,platinum resistance and interleukin-17.Among the 13 genes,claudin 4(CLDN4),secretory leukocyte peptidase inhibitor(SLPI)and baculoviral IAP repeat containing 5(BIRC5)were associated with the prognosis of ovarian cancer.Cell experiments showed that Aidi injection significantly inhibited the proliferation of ovari-an cancer cell,promoted the expression of BIRC5,a protective target of ovarian cancer,while significantly decreased the levels of ovarian cancer risk factors CLDN4 and SLPI.Conclusion Aidi injection may achieve multi-component,multi-target and multi-pathway anti-ovarian cancer and combination chemotherapy by affecting the expression of CLDN4,SLPI and BIRC5.

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Objective To comprehensively analyze the effectiveness of exercise training-based respiratory rehabilitation therapy on patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). MethodsLiterature on randomized controlled trials of exercise training-based respiratory rehabilitation therapy for pneumoconiosis patients published from the establishment of the database to July 2023 was retrieved from academic systems such as the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database, and China Biology Medicine using bibliometrics method. The RevMan 5.4 software was used for meta-analysis of the selected literatures. Subgroup analysis was conducted to explore the source of study heterogeneity. The funnel plot method was used to test publication bias. Results A total of 55 articles were included, involving 2 436 pneumoconiosis patients in the experimental group and 2 405 pneumoconiosis patients in the control group. The result of random or fixed effect model showed that the six minutes walking distance, the total score of Short from Health Survey-36, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁/FVC, arterial partial pressure of oxygen of pneumoconiosis patients increased after respiratory rehabilitation therapy (all P<0.05), while the total score of the St. George's Respiratory Questionnaire and arterial partial pressure of carbon dioxide decreased compared with the conventional treatment (all P<0.05). The result of subgroup analysis showed that the total score of the St. George's Respiratory Questionnaire, FEV₁, and the index of arterial partial pressure of oxygen of pneumoconiosis patients was better in the rehabilitation treatment for ≥six months compared with those

Objective:To investigate the relationship between three-dimensional choroidal vascularity index (3D CVI) and the severity of diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA).Methods:A cross-sectional study was conducted.A total of 139 eyes of 139 subjects, including 115 eyes with diabetes mellitus and 24 control eyes without diabetes, were enrolled in the Second People's Hospital of Hefei from March to December 2022.DR was graded according to the standard seven-field ETDRS color fundus photographs.Eyes with diabetes mellitus were divided into non-DR (NDR) group (34 eyes), non-proliferative DR (NPDR) group (42 eyes), NPDR with diabetic macular edema (DME) group (21 eyes) and PDR group (18 eyes).3D CVI in central fovea 1 mm (C1) and parafoveal 3 mm (C3), choroidal vascular volume (CVV), and choroidal thickness were measured by SS-OCTA in the area of 3 mm×3 mm centered on the fovea using the built-in automated quantification software.Parafoveal region was divided into superior, inferior, temporal and nasal quadrants, and 3D CVI of the different quadrants was detected.3D CVI was defined as the ratio of CVV to total choroidal volume.The monocular data were analyzed to compare 3D CVI among the five groups, and multiple linear regression analysis was used to evaluate the influencing factors.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University (No.2022064).All subjects were aware of the study purpose and agreed to participate the study.Results:There were significant differences in 3D CVI-C1 and 3D CVI-C3 among all groups ( F=3.103, 3.036, both at P<0.05).In PDR group, 3D CVI-C1 was lower than in non-DR group, and 3D CVI-C3 was lower than in control group and non-DR group, with statistically significant differences (all at P<0.05).There were significant differences in 3D CVI in the inferior and nasal quadrants among all groups ( F=2.714, 4.020, both at P<0.05).In PDR group, 3D CVI in the inferior quadrant was lower than that in non-DR group, and 3D CVI in nasal quadrant in PDR group was lower than that in control group, non-DR group, NPDR group and NPDR with DME group, with statistically significant differences (all at P<0.05).Multiple linear regression showed that after controlling for age, course of disease and glycosylated hemoglobin, the severity of DR was the influencing factor of 3D CVI in fovea and parafovea.PDR eyes had the greatest impact on 3D CVI in fovea and parafovea.Compared with non-DR eyes, there was a -0.019(95% CI: -0.031--0.007, P=0.003) decrease in central foveal 3D CVI and a -0.019(95% CI: -0.030--0.008, P=0.001) decrease in parafoveal 3D CVI in PDR eyes, followed by a 0.014(95% CI: -0.027-0.000, P=0.044) decrease in central foveal 3D CVI in NPDR with DME eyes. Conclusions:Macular foveal 3D CVI correlates with DR severity, and a decrease in 3D CVI of large vessels in the macular choroid may be a sensitive indicator of DR exacerbation.

ObjectiveTo investigate protective effect of Arctium lappa root aqueous extract （ALR-AE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats based on protein kinase B/nuclear transcription factor-κB （Akt/NF-κB） signaling pathway. MethodRats were randomly divided into 5 groups， namely normal group， model group， ranitidine group （35 mg·kg^-1）， ALR-AE low dose group （50 mg·kg^-1， ALR-AE-L group） and ALR-AE high dose group （100 mg·kg^-1， ALR-AE-H group）. Different doses of ALR-AE were orally administered twice daily for three consecutive days before the animals were subjected to HCl/EtOH （60% ethanol in 150 mmol·L^-1 HCl） to induce acute gastric ulcer. For the gastric tissue samples， the ulcer surface was recorded by electronic imaging technique， and then the ulcer inhibition rate was calculated using ImageJ 1.8.0， hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological changes and mucoprotein distribution， respectively. The levels of oxidative stress factors of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in rat gastric tissues were determined by colorimetric method， the levels of pro-inflammatory mediators of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β were determined by enzyme linked immunosorbent assay （ELISA）， protein levels of phosphorylation and non-phosphorylation of Akt， NF-κB p65， NF-κB inhibitor protein α （IκBα） and IκB kinase α （IKKα） were evaluated by Western blot. ResultCompared with the normal group， the gastric tissue of the model group was severely damaged， and the area of gastric ulcer were significantly enlarged （P<0.01）， the levels of MDA， TNF-α， IL-6 and IL-1β in gastric tissue were significantly increased （P<0.01）， levels of GSH-Px and SOD were significantly decreased （P<0.01）， and phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα in gastric tissue were significantly increased （P<0.01）. Compared with the model group， ALR-AE significantly attenuated HCl/EtOH-induced gastric tissue damage， significantly increased ulcer inhibition rate （P<0.01）， and dose-dependently reduced the levels of MDA， TNF-α， IL-6 and IL-1β （P<0.05， P<0.01）， and elevated GSH-Px and SOD levels （P<0.01）， ALR-AE-L group could significantly inhibit the phosphorylation levels of Akt （P<0.05）， and ALR-AE-H group could significantly inhibit phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα （P<0.05， P<0.01）. ConclusionALR-AE has a significant protective effect on HCl/EtOH-induced acute gastric ulcers in rats， and its mechanism may be related to the inhibition of inflammatory mediator expression and reduction of oxidative stress levels mediated by Akt/NF-κB signaling pathway.

ObjectiveTo investigate the mechanism of protective effect of ethanol extracts of Hemsleya chinensis （HC-EE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats. MethodLipopolysaccharide （LPS）-induced RAW264.7 cells were used to evaluate inhibitory effect of HC-EE on the production of inflammatory mediators in vitro. A rat acute gastric ulcer model induced by HCl/EtOH （60% ethanol in 150 mmol·L^-1 HCl） was used to evaluate protective effect of HC-EE on acute gastric ulcer. Rats were divided into five groups， including normal group， model group， HC-EE low dose （HC-EE 30， 30 mg·kg^-1） group， HC-EE high dose （HC-EE 60， 60 mg·kg^-1） group and ranitidine （35 mg·kg^-1） group. For model and drug-treated groups， vehicle solvent or drugs were orally administered twice daily for 7 consecutive days before the rats were subjected to HCl/EtOH to induce acute gastric ulcer. After being anesthetized， ulcer surface of each rat was obtained and recorded using electronic imaging technology， and the ulcer inhibition rate was calculated by ImageJ 1.8.0. Hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological histological changes in rats. Content of nitric oxide （NO） in cell culture medium was measured by the Griess method. The levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-6， vascular cell adhesion molecule-1 （VCAM-1） and prostaglandin E₂ （PGE₂） in rat serum （or cell culture medium） were determined by enzyme linked immunosorbent assay （ELISA）. The protein expressions of phosphorylation （p）-p38 mitogen activated protein kinase （MAPK）/p38 MAPK and p-nuclear transcription factor-κB （NF-κB） p65/NF-κB p65 in rat gastric tissue were detected by Western blot. ResultIn vitro assay showed HC-EE could significantly down-regulate the expressions of NO， TNF-α， IL-1β， IL-6 and VCAM-1 in LPS-induced cells （P<0.05， P<0.01）. In vivo experimental results showed that， compared with the normal group， gastric tissue of the model group was severely damaged， and the area of gastric ulcer was significantly enlarged， levels of TNF-α， IL-6 were significantly increased （P<0.01）， and the level of PGE₂ was significantly decreased （P<0.01）， the phosphorylation levels of of p38 MAPK， NF-κB p65 in gastric tissue were significantly increased （P<0.01）. Compared with the model group， HC-EE dose-dependently improved HCl/EtOH-induced gastric tissue injury and inflammatory cell infiltration， and it could increase ulcer inhibition rate， significantly decreased the release of TNF-α and IL-6 （P<0.01）， HC-EE 60 group could increase the content of PGE₂ （P<0.05）， and significantly inhibit the phosphorylation levels of p38 MAPK and NF-κB p65 （P<0.05， P<0.01）. ConclusionHC-EE can exert protective effect on HCl/EtOH-induced acute gastric ulcer in rats， and its mechanism may be related to the inhibition of expression of inflammatory mediators mediated by p38 MAPK/NF-κB signaling pathway.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Objective:To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence.Methods:After excluding individuals with missing educational levels and cancer information at baseline, 446?772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer.Results:During a median follow-up of 7.13 years, 1?994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer ( HR=0.88, 95% CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self‐report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95% CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with β coefficients (95% CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score ( β=0.042, 95% CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95% CI: 31.802%-51.659%) and 1.784% (95% CI: 0.405%-3.713%), respectively. Conclusion:Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

Necrotizing pneumonia(NP)is a serious pulmonary complication of community acquired pneumonia(CAP), and can occur in adults and children.NP was first reported in adults, and in recent years the incidence of NP in children is growing.Until now, there is little description compare the etiology, clinical manifestation, auxiliary examination, risk factors, treatment and prognosis in children and adults with necrotizing pneumonia.This article systematically reviews several aspects of NP between children and adults, which would be helpful for diagnosing and treating NP in different age groups.