AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Objective To investigate the value of serum cell cycle protein-dependent kinase 1(CDK1)and aurora kinase A(AURKA)in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 50 HBV-HCC patients,50 patients with hepatitis B virus-related liver cirrhosis(HBV-LC),and 50 chronic hepatitis B(CHB)patients who were hospitalized in Department of Gastroenterology,Gansu Provincial Hospital,from June 2022 to December 2023 were enrolled,and 50 healthy individuals,matched for age and sex,who received physical examination at Physical Examination Center during the same period of time were enrolled as control group.Related data were recorded for all patients,including age,sex,complications,and the results of routine blood test,liver function,and coagulation for the first time after admission.ELISA was used to measure the serum levels of CDK1 and AURKA.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA,and the receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC.Results There were significant differences in liver function parameters between the HBV-HCC patients and the control group(all P<0.05);there were significant differences between the CHB group and the HBV-HCC group in albumin,Glb,direct bilirubin,aspartate aminotransferase(AST),gamma-glutamyl transpeptidase(GGT),and alkaline phosphatase(all P<0.05);there were significant differences between the HBV-LC group and the HBV-HCC group in Glb,AST,and GGT(all P<0.05).The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group,the CHB group,and the control group(all P<0.05).There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients(r=0.526 6 and 0.815 2,P<0.001).With the control group as reference,CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC,with a sensitivity of 92.86%and a specificity of 75%,and AURKA had an AUC of 0.886 6 in the diagnosis of HCC,with a sensitivity of 95.80%and a specificity of 74%.With the CHB group as reference,CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC,with a sensitivity of 93.75%and a specificity of 75%,and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 91.67%.With the HBV-LC group as reference,CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC,with a sensitivity of 66.67%and a specificity of 54.17%,and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 47.92%.Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease,and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

ObjectiveTo demonstrate the long-term effect of Yishi Therapy for primary tinnitus and analyze the factors affecting the effectiveness. MethodsWe conducted long-term follow-ups of primary tinnitus cases treated with Yishi Therapy during 1 January 2017 to 30 June 2023 by face-to-face， online and telephone between 1 July 2023 and 31 January 2024， to understand the final regression of primary tinnitus and lifestyle changes. We retrospectively analysed the basic data of patients before treatment， and statistically analysed the recovery rate and overall effective rate of tinnitus treated by the Yishi Therapy， and the factors affecting the effectiveness such as lifestyle， age， duration of disease， gender， tinnitus location， severity of tinnitus， accompanying symptoms and complications on the overall effective rate. ResultsA total of 496 cases of primary tinnitus completed follow-ups successfully， and the total Tinnitus Evaluation Questionnaire （TEQ） at follow-up was significantly lower than that before treatment （P＜0.001）. Among the 496 cases， 101 （20.36%） cases cured， 189 （38.10%） cases showed significant improvement， 116 （23.39%） cases were effective， 90 （18.15%） cases were ineffective， and the overall effect rate was 81.85% （406/496）. At follow-up， the score of lifestyle was higher than that before treatment （P＜0.001）. Grouped by the score of lifestyle at follow-up， the effective rates of better lifestyle group and poor lifestyle group were 97.53% （237/243） and 66.80% （169/253）， respectively， with statistical significance （P＜0.001）. Grouped by the mean value of the difference in lifestyle scores before and after treatment， the effective rates of the group with greater lifestyle adjustment and the group with smaller adjustment were 97.55% （239/245） and 66.53% （167/251）， respectively， and the differences were statistically significant （P＜0.001）. Binary logistic regression showed that the better lifestyle， the greater lifestyle adjustment and the severity of tinnitus were positively correlated with the total effective rate of tinnitus （P＜0.001）， while older and hearing loss were negatively correlated with the total effective rate of tinnitus （P＜0.05）. ConclusionYishi Therapy on primary tinnitus shows good long-term effect， lifestyle， severity of tinnitus， hearing loss or not， age are the relevant factors affecting the efficacy of tinnitus， lifestyle is the main factor affecting clinical efficacy.

Objective:To summarize the clinical characteristics、diagnosis and treatment experience of children with reobstruction after pyeloplasty.Methods:A retrospective analysis was conducted on patients admitted to the Department of Urology, Beijing Children's Hospital from January 2015 to April 2022. Due to the unrelieved hydronephroplasty after the primary pyeloplasty, the anterior and posterior diameter of the pelvis was larger than that before the primary operation. Intravenous pyelography and diuretic renal radionuclide scanning confirmed the diagnosis of ureteropelvic reobstruction. Or underwent reoperation after undergoing puncture angiography for reobstruction. Fifty-four children were included in the study, 47 males (87.03%) and 7 females (12.96%), with a median age of 51.67(21.30, 117.24)month, and, 38 cases (70.37%) on the left side and 16 cases (29.63%) on the right side. The primary operation was open pyeloplasty (POP) in 20 cases and laparoscopic pyeloplasty (PLP) in 34 cases. 45 patients underwent primary operation in our hospital, and 9 patients were referred from other hospitals after primary operation. The interval between reoperation and initial operation was 7.25(6.15, 15.40)month. There were 28 cases with clinical symptoms before operation, and 26 cases without symptoms but reobstruction on imaging. 21 cases presented with recurrent abdominal pain, nausea and vomiting, and 7 cases presented with recurrent fever and urinary tract infection. All 54 patients underwent re-pyeloplasty after definite diagnosis of re-obstruction. In order to further study the feasibility of RLP, patients in the two groups were divided into RLP and ROP groups according to different surgical procedures. In the RLP group, there were 8 males (72.72%) and 3 females (27.28%). The median age was 82.21(49.83, 114.05) months, and obstruction was located on the left side in 8 cases (72.72%) and the right side in 3 cases (27.28%). There were 3 cases (27.28%) with POP and 8 cases (72.72%) with PLP. The time between the second operation and the primary operation was 12.83 (6.34, 16.86) months. APD before operation was 5.18 (4.25, 6.14) cm. There were 43 cases in the ROP group, including 38 males (88.37%) and 5 females (12.63%). The median age was 52.32 (26.62, 77.35) months; Obstruction was located on the left side in 31 cases (72.09%) and the right side in 12 cases (27.91%). The primary operation was performed in 19 cases (44.19%) with POP and 24 cases (55.81%) with PLP. The time between the second operation and the primary operation was 10.02 (8.03, 15.51) months. Preoperative APD was 5.42 (5.14, 5.90) cm. The causes of obstruction were found in the second operation: there were 28 causes (51.85%) of scar hyperplastic anastomotic stenosis, 7 cases (12.96%) of residual ectopic vascular compression, 8 cases (14.81%) of high ureteral anastomosis, 7 cases (12.96%) of ureteral adhesion distortion, and 4 cases (7.41%) of other causes (1 case of medical glue shell compression, 1 case of luminal polypoid hyperplasia, and 2 cases of complete luminal occlusion). Operation time, postoperative complications, APD, APD improvement rate (PI-APD), renal parenchyma thickness (PT), anteroposterior pelvis diameter/renal parenchyma thickness (APD/PT) at 3 and 6 months after operation were compared between RLP and ROP groups.Results:In this study, 54 patients were followed up with an average follow-up time of (34.41±20.20)month. APD of 3 months after pyeloplasty was 3.29(3.03, 3.52) cm, which was statistically significant compared with 5.45(5.13, 5.77)cm before pyeloplasty ( P=0.02). APD/PT changed from preoperative 21.71(21.08, 31.77)to 5.40(4.79, 6.79)3 months after surgery, and the difference was statistically significant ( P=0.03). The APD improvement rate was 37%(33%, 42%) 3 months after surgery and 49%(44%, 54%) 6 months after surgery. Among the 54 patients, 3 had lumbago and fever after clamping the nephrostomy tube, and 3(5.55%) had sinus angiography indicating that obstruction still existed and required reoperation. Therefore, the success rate of repyeloplasty in this group was 94.45%. Comparing RLP group and ROP group, operation time in RLP group was longer than that in ROP group [169.13(113.45, 210.66)]min vs. 106.83(103.14, 155.32)min, P=0.02]. The length of hospitalization in RLP group was shorter than that in ROP group [7.45(5.62, 9.28)d vs.11.64(10.45, 15.66)d, P=0.03], and the difference was statistically significant. The improvement rate of APD 3 months after surgery was compared between the two groups [30.48%(19.81%, 41.16%) vs.39.96%(35.16%, 47.76%), P=0.15], and the improvement rate of APD 6 months after surgery was compared between the two groups [48.00%(27.19%, 48.81%) vs.52.27%(46.95%, 56.76%), P=0.05], there was no significant difference in the success rate of operation between the two groups (90.90% vs. 95.34%, P=0.63). Conclusions:The common cause of reobstruction after pyeloplasty is cicatricial adhesion stenosis. The operation is challenging, but repyeloplasty can effectively relieve the obstruction and the overall success rate is 94.45%. RLP is a safe and effective surgical method for the treatment of reobstruction, which can achieve comparable surgical results with ROP.

OBJECTIVES: To construct a quantitative index system with the integrated medical and nursing care assessment for the elderly service needs, this system can assess the cost of medical and care services accurately and objectively, so as to provide scientific basis for the allocation of old-age service resources in China. METHODS: Based on the survival needs of the Existence, Relation and Growth theory, an index system is constructed through literature analysis, group discussion, and expert correspondence. Analytic hierarchy process was used to determine the weights of indicators at all levels. The 3-grades service items corresponding to each index were quantified through the measurement of working hours, and the medical and nursing care needs of 624 disabled/demented elderly people over 60 years old in Changsha were investigated to evaluate their reliability and validity. RESULTS: The authoritative coefficients of the 2 rounds of expert correspondence were 88.5% and 88.6%, respectively, and the opinion coordination coefficients were 0.159 and 0.167, respectively. The final quantitative evaluation index system included 4 first-level indicators, 17 second-level indicators, and 105 third-level indicators. The service time of doctor ranged from 6.01 to 22.64 min, the service time of nurses ranged from 0.77 to 24.79 min, and the service time of caregiver ranged from 0.12 to 51.88 min. The Cronbach's αcoefficient was 0.73, the split-half reliability was 0.74, the content validity was 0.93, and the calibration validity was 0.781. CONCLUSIONS The quantitative evaluation index system of medical and nursing service need for the elderly can be used to accurately evaluate the medical and nursing service need.
Humans ; Aged ; Middle Aged ; Reproducibility of Results ; Surveys and Questionnaires ; Delphi Technique ; Nursing Care ; China

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells， unbalanced production and degradation of extracellular matrix proteins， and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma， becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years， which mainly involves abnormal iron metabolism， lipid peroxide accumulation， and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety， wide therapeutic effects， and easy access compared with Western medicine. Therefore， The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis， providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.

BACKGROUND: SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare primary lung malignancy. These diseases are not listed separately in the 2021 World Health Organization (WHO) classification of lung neoplasms, but they have special morphological, immunophenotypic and molecular genetic characteristics. This study aims to improve understanding of SMARCA4-dNSCLC by discussing the clinicopathological features, diagonosis and differential diagnosis of the disease. METHODS: The clinical and imaging data of 9 cases of SMARCA4-dNSCLC diagnosed in Shanghai Changhai Hospital from January 2020 to March 2022 were collected. The clinicopathological features were analyzed by histological and immunohistochemical staining, and the literature was reviewed. RESULTS: The median age of 9 patients was 65 years old. Six men were smokers. The average maximum diameter of tumor was 3.3 cm. Six cases had been metastasized. The imaging showed that it was an infiltrating mass with unclear boundary and 3 cases invaded the pleura. Nine cases were diagnosed as SMARCA4-dNSCLC, which mainly showed three pathological forms including classic lung adenocarcinoma, mucinous adenocarcinoma and poorly differentiated carcinoma. Poorly differentiated tumor cells are epithelioid, syncytial or rhabdomyoid, the cytoplasm was rich, the cytoplasm could be completely transparent to eosinophilic, eosinophilic globules or small abscesses could be seen, showing solid flakes, with more inflammatory cells and flake necrosis in the stroma. Immunohistochemistry showed that SMARCA4 was negative in all cases and eight cases demonstrated cytokeratin 5.2 (CAM5.2) and cytokeratin 7 (CK7) was diffusely strongly positive, p40 was negative, thyroid transcription factor-1 (TTF-1) was negative in 6 cases, partially positive in 2 cases and diffusely positive in 1 case. CONCLUSIONS SMARCA4-dNSCLC is a rare subtype of lung cancer with complex and diverse pathological morphology. The characteristic of immunohistochemical phenotype can assist in the diagnosis.
Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; China ; DNA Helicases/genetics* ; Humans ; Lung Neoplasms/pathology* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Objective: To analyze the possible responses of parents of young children to Child sexual assault (CSA) and the potential influencing factors, so as to provide evidence for prevention programs of CSA. Methods: Part of the data from "2016-2020 Child Injury Prevention Project" was used to analyze responses to CSA among parents of children younger than 3rd grade in primary school by chi square test and Logistic regression analysis. Results: A total of 4 072 parents were included in the analysis. Among them, 86.8% of parents chose "to solve problems together", 51.0% of parents taking children to a "psychologist", 4.9% of parents "scolding children for being too careless", 2.9% of parents "letting child not disclose abuse" and 6.5% of parents chose "other" coping methods. Parents with foreign nationality [OR(95%CI)=2.58(1.25-5.15)] and lower education level (OR=0.26-0.64) tend to "blame" their children. Mothers [(OR(95%CI)=0.54(0.33-0.90)], higher parental education level (OR=0.27-0.72) were more reluctant to encourage their children to keep quiet. Mothers [OR(95%CI)=1.73(1.32-2.27)], older children (OR=1.33-1.78) and parents with higher education level (OR=1.65-2.99) tend to "accompany". Parents aged 30 or more, and from high school/technical school/technical secondary school tend to take their children to see a "psychologist" [OR(95%CI)=1.39(1.14-1.71), 1.79(1.26-2.53)]. Conclusion Parents universally pay attention to the physical and mental health of children after CSA, but some parents still take negative coping methods, e.g. "blame" and "not disclose". Parenting educational level, duration of parent-child communication and age of children are primary factors associated with parental responses to child sexual assault. This study suggests that prevention secondary injury following child sexual assault should be farther strengthened, while fully considering the characteristics of the educated objects.