This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

OBJECTIVES: To investigate the expression of apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and its effects on proliferation and apoptosis of PTC cells. METHODS: The expression level of APOC1 in PTC and its impact on prognosis were analyzed using GEPIA 2 and Kaplan-Meier databases. Immunohistochemistry (IHC) and Western blotting were used to detect the expression of APOC1 in PTC and adjacent tissues and in 3 PTC cell lines and normal thyroid Nthyori 3-1 cells. In TPC-1 and BCPAP cells, the effect of Lipofectamine 2000-mediated transfection with APOC1 siRNA or an APOC1-overexpressing plasmid on cell growth and colony formation ability were examined by observing the growth curves and using colony-forming assay. The changes in cell cycle and apoptosis of the transfected cells were analyzed with flow cytometry. RT-qPCR and Western blotting were used to detect the changes in expressions of P21, P27, CDK4, cyclin D1, Bcl-2, Bax, caspase-3 and caspase-9 and the key proteins in the JAK2/STAT3 signaling pathway. RESULTS: APOC1 expression was significantly higher in PTC tissues and the 3 PTC cell lines than in the adjacent tissues and Nthyori 3-1 cells, respectively. In TPC-1 and BCPAP cells, APOC1 knockdown obviously reduced cell proliferative activity, increased the percentage of G0/G1 phase cells, lowered the percentages of S and G2 phase cells, promoted cell apoptosis, and downregulated mRNA and protein expression levels of CDK4, cyclin D1 and Bcl-2 and the protein levels of p-JAK2 and p-STAT3. APOC1 overexpression in the cells produced the opposite effects on cell proliferation, apoptosis, cell cycle and the mRNA and protein expressions. The application of AG490, a JAK2 inhibitor, strongly attenuated APOC1 overexpression-induced activation of the JAK2/STAT3 signaling pathway in BCPAP cells. CONCLUSIONS APOC1 overexpression promotes proliferation and inhibits apoptosis of PTC cells possibly by activating the JAK2/STAT3 signaling pathway and accelerating cell cycle progression.
Humans ; Apoptosis ; Cell Proliferation ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Janus Kinase 2/metabolism* ; Thyroid Neoplasms/pathology* ; Thyroid Cancer, Papillary ; Cell Line, Tumor ; Carcinoma, Papillary

Objective:There are significant differences in the distribution of gut microbiota among different populations in different regions.This study mainly explores the structure and distribution of gut microbiota between cow's milk protein allergy（CMPA）children and healthy children in Xiamen,Fujian,and further explores the correlation between gut microbiota and the occurrence and development of CMPA.Methods:Fecal samples have been collected from 30 children with CMPA diagnosed at Xiamen Children’s Hospital from June 2022 to March 2023,and fecal samples from 30 healthy children of the same age have also been collected.The structure and distribution of gut microbiota between the two groups were analyzed using 16S rDNA gene sequencing and bioinformatics analysis.Results:The structure and distribution of gut microbiota between CMPA children and healthy children were quite different.There were no significant differences in α diversity index between groups（ P>0.05）.The analysis of similarities test results showed that there was a significant difference in the distribution of gut microbiota between two groups（ R=0.037, P<0.05）.The β diversity index from PCA showed that there was a significant difference in bacterial community structure between two groups（ P<0.05）.Compared with healthy children,the abundance of Akkermansia in CMPA children was significantly decreased and the abundance of Corynebacterium was significantly increased in CMPA children.LEfSe showed that Proteobacteria were mainly enriched in CMPA children,while Lachnospiraceae were mainly enriched in healthy children.In addition,KEGG analysis showed that the top enrichment of 20 pathways,such as Fructose and mannose metabolism,was significantly decreased in CMPA children（ P<0.05）.COG analysis showed that the enrichment of pathways such as Galactose mutarotase and related enzymes was significantly decreased in CMPA children（ P<0.05）,while the enrichment of pathways including Predicted metal-sulfur cluster biosynthetic enzyme and other two pathways was significantly increased（ P<0.05）. Conclusion:There are significant differences in the structure and distribution of gut microbiota between CMPA children and healthy children,suggesting that a strong correlation between the occurrence and development of CMPA and the gut microbiota.

Purpose: This study aims to elucidate the longitudinal alterations in frailty and health-related quality of life experienced by elderly patients undergoing surgical treatment for esophageal cancer. Additionally, it seeks to ascertain the impact of preoperative frailty on postoperative health-related quality of life over time. Methods: 131 patients were included in the prospective study. Patients' frailty and health-related quality-of-life were assessed utilizing the Tilburg and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at preoperative, 1 week, 1 month, and 3 months, postoperatively. Statistical analyses were performed using generalized estimating equations, repeated-measures analysis of variance, and linear mixed models (LMMs). Results: Out of 131 patients, 28.2% had frailty before surgery, and the prevalence of frailty consistently higher after surgery compared with baseline (67.9%, 51.9%, and 39.7%). There was no significant change in frailty scores in preoperative frail patients within 3 months following surgery (p = .496, p < .999, p < .999); whereas in preoperative non-frail patients, the frailty scores increased at 1 week (p < .001) and then decreased at 1 month (p = .014), followed by no change at 3 months. In addition, preoperative frail patients had significantly worse global quality-of-life (β = −4.24 (−8.31; −.18), p = .041), physical functioning (β = −9.87 (−14.59; −5.16), p < .001), role functioning (β = −10.04 (−15.76; −4.33), p = .001), and social functioning (β = −8.58 (−15.49; −1.68), p = .015), compared with non-frail patients. Conclusions A significant proportion of participants exhibited a high prevalence of preoperative frailty. These patients, who were preoperatively frail, exhibited a marked reduction in health-related quality-of-life, a more gradual recovery across various functional domains, and an increased symptom burden during the follow-up period. Therefore, it is crucial to meticulously identify and closely monitor patients with preoperative frailty for any changes in their postoperative physiology, role, and social functioning.

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
Animals ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species ; Tumor Suppressor Protein p53/genetics* ; Signal Transduction ; Liver ; Aging ; Cell Cycle Proteins ; Interleukin-6

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Objective:To understand the clinical application of diet management evidence during dialysis in maintenance hemodialysis (MHD) patients, analyze facilitators/barriers and develop intervention strategies, so as to provide reference for the conversion of evidence-based evidence into clinical practice.Methods:From January to February 2022, 131 persons related to diet management of MHD patients during dialysis were selected from Suzhou Hospital Affiliated to Nanjing Medical University (Suzhou Municipal Hospital) by convenience sampling, including 3 hemodialysis doctors, 7 hemodialysis nurses, and 121 MHD patients. We introduced 7 pieces of evidence of diet management for MHD patients during dialysis, developed 17 review indicators based on the evidence, and conducted a clinical status review. Based on the review results, we conducted an analysis of facilitators and barriers.Results:The clinical compliance rate of 17 review indicators ranged from 0 to 71.29%. The standardized scores of patients' diet management knowledge, beliefs, and behaviors were 26.00%, 61.88%, and 67.82%, respectively, while the standardized scores of medical and nursing diet management knowledge, beliefs, and behaviors were 42.20%, 68.00%, and 64.00%, respectively. The facilitators included the high validation importance and feasibility of each item in the evidence, the willingness of medical and nursing staff and patients to learn about diet management knowledge, the availability of ordering services in the cafeteria, the availability of a hemodialysis information system, and the pre dialysis evaluation and post dialysis evaluation stages. Barriers mainly included unclear explanation of evidence items, lack of practical details, lack of ways to learn diet management knowledge, single form of education channels, conflicts with patients' traditional dietary habits, difficulty in obtaining food that met the requirements of the conditions, lack of a comprehensive diet management process, lack of diet management teams, and lack of evaluation standards for diet management and lack of practical guidance.Conclusions:The evidence of diet management during dialysis in MHD patients has not yet been effectively translated into clinical practice. An evidence-based practice plan should be constructed based on the analysis of facilitators/barriers and intervention strategies to shorten the gap between clinical practice and evidence.

Objective To investigate the current status of cytotoxicity and mechanical properties of the prosthetic liner on the market in China.Methods Six kinds of liner were collected, namely domestic 6 mm thick foam liner (A), domestic 5 mm thick EVA foam liner (B), German 5 mm thick EVA foam liner (C), Germany 12 mm thick PE foam liner (D), Iceland 3 mm thick silicone liner (E) and Germany 4 mm thick gel liner (F). Microscopic observation and thiazole blue colorimetry were used to detect the cytotoxicity. The content of small organic molecules was determined by the consumption of potassium permanganate. The tensile strength, elongation at break (%), and 100% tensile strength of the prosthetic liner were tested by material mechanics testing machine. The hardness was tested using the Shore hardness tester oo type.Results The cytotoxicity was grade 2 for prosthetic liners A, B, C and D, and was grade 0 for E and F. The redox substance content of prosthetic liners A、B、C exceeded 150 mg/kg. Except the prosthetic liner C, the hardness of the other products were all ≤ 70 HA. Except prosthetic liner D, the tensile strengths were > 1 MPa, breaking elongations were > 120.0%, 100% tensile strengths were > 0.9 MPa for other products.Conclusion Due to materials and production processes, the cytotoxicity and mechanical properties of the six samples are quite different.

ObjectiveTo investigate the tongue movement of swallowing food with different volumes and viscosities in healthy adults by B/M ultrasound. MethodsFrom November 1, 2021 to April 15, 2022, 61 healthy adults were recruited from those who underwent ultrasound examination in Beijing Bo'ai Hospital. The objects were ask to swallow 5 mL water, 15 mL water, 5 mL semi-liquid yogurt and 5 mL solid yogurt. Then B/M ultrasound was used to record the phase I time, phase II time, maximum amplitude and maximum velocity of tongue movement. ResultsThe phase I time was the least as swallowing 5 mL water (|Z| > 3.871, P < 0.001). The phase II time was less asswallowing 5 mL water than that of swallowing 15 mL water and 5 mL semi-liquid yogurt (|Z| > 2.61, P < 0.001). The maximum amplitude of tongue movement was the most as swallowing 15 mL water (|Z| > 8.888, P < 0.001). There was no significant difference in the maximum velocity of tongue movement among the four swallowing tasks (χ² = 0.833, P > 0.05). ConclusionFood of different viscosities and different volumes can affect tongue movement. The use of B/M ultrasound is an easy, radiation-free and cost-effective method for the assessment of swallowing.

Objective:To make Excel spreadsheet of arterial blood gas analysis to judge the types of acid-base imbalance quickly and accurately, and guide the clinical treatment of acid-base disorders.Methods:According to the Henderson-Hasselbalch equation, the compensation formula of acid-base imbalance prediction, the theory of acid-base balance and the related research progress, the analysis process of acid-base balance disorder was settled, and the IF function in Microsoft Office Excel 2003 was used to edit the formula to make Excel spreadsheet for arterial blood gas analysis.Once the pH value, artery blood carbon dioxide pressure (PaCO 2), actual bicarbonate (HCO 3-), sodiumion (Na + ), chlorineion (Cl -) and compensatory time-limited parameters were input, the types of acid-base imbalance can be shown.Arterial blood gas analysis of 185 cases from intensive care unit at Xuzhou Central Hospital was determined by Excel spreadsheet group and manual group respectively, the results and time of judging the type of acid-base imbalance were compared between two groups for statistical analysis. Results:The results of acid-base imbalance between two groups were compared, and 42 cases were normal and simple acid-base and the consistent rate was 100%, double acid-base imbalances of 107 cases with the consistent rate of 97.20%, triple acid-base imbalances of 36 cases with the consistent rate of 91.67%.After Kappa consistency test (Kappa value=0.944) and Pair chi-square Test (McNemar-Bowker Test)( P=0.223), the results of two groups were consistent.It took less time to judge the results of normal or simple acid-base imbalance[(32.32±4.26)s vs.(75.88±19.22)s], double acid-base imbalance[(31.28±5.31)s vs.(137.56±37.64)s] and triple acid-base imbalance[(32.98±4.23)s vs.(315.09±89.37)s] by the Excel spreadsheet group compared with the manual group, and the differences were statistically significant ( P<0.01). Conclusion:The automatic judging of Excel spreadsheet for arterial blood gas analysis can quickly and accurately determine the types of acid-base imbalance in arterial blood gas analysis and has more advantages for triple acid and base imbalance especially with simple interface and simple operation.And it can avoid the missing judgment of acid and base imbalance when pH is 7.35 to 7.45.