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

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To observe the different administration methods of methoxamine on the body temperature protection of patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The clinical data of 278 patients underwent OPCABG from January 2019 to December 2021 in Jinzhou Central Hospital were retrospectively analyzed, and the patients were used the methoxamine during the operation. Among them, 157 cases were given methoxamine by continuous intravenous infusion (continuous intravenous infusion group), and 121 cases were given methoxamine by fractional intravenous infusion in stages (fractional intravenous infusion group). The changes of mean arterial pressure (MAP) and heart rate during operation were recorded, and the fluctuation rate of MAP was calculated. The dosage of methoxamine, use time of variable temperature blanket, time from the end of operation to waking up and occurrence of adverse reactions such as hypothermia, rigors, coagulation disorders and renal insufficiency were recorded.Results:During anesthesia, the fluctuation rate of MAP in continuous intravenous infusion group was significantly lower than that in fractional intravenous infusion group: (16.62 ± 3.17)% vs. (23.53±3.69)%, and there was statistical difference ( P<0.05). The MAP and heart rate of continuous intravenous infusion group were more stable at each time point than that of fractional intravenous infusion group. The use time of variable temperature blanket, and incidences of hypothermia, rigors in continuous intravenous infusion group were significantly lower than those in fractional intravenous infusion group: (86.17 ± 19.66) min vs. (146.72 ± 29.37) min, 2.55% (4/157) vs. 9.92% (12/121) and 1.91% (3/157) vs. 8.26% (10/121), and there was statistical difference ( P<0.01 or <0.05); there were no statistical differences in dosage of methoxamine, time from the end of operation to waking up and incidence of coagulation disorders between two groups ( P>0.05); Renal insufficiency did not occur in both groups. Conclusions:Continuous intravenous pumping of methoxamine can obviously reduce the heat loss of human body, enhance the insulation effect of other insulation measures, and reduce the incidence of hypothermia in patients underwent OPCABG.

ObjectiveTo investigate the effect of chorionicity， gestational age at birth and birth weight discordance on neonatal outcomes in twin pregnancies. MethodsWe conducted a population-based retrospective study of monochorionic diamniotic （MCDA） twin pregnancies and dichorionic diamniotic （DCDA） twin pregnancies who were admitted in the First Affiliated Hospital， Sun Yat-sen University from January 2015 to December 2020. A total of 1504 live-born twins were included， with 386 cases in MCDA group and 1118 cases in DCDA groups， respectively. The comparison of neonatal outcomes between MCDA and DCDA twins was performed using t-test， Wilcoxon rank sum test， Chi-square test or Fisher’s exact test. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight discordance and sex on neonatal outcomes. There were 168 live-born twins affected by inter-twin birth weight discordance≥25%， with 96 cases in MCDA group and 72 cases in DCDA groups， respectively. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight light or heavy （small twin or large twin） of the twin and sex on neonatal outcomes. ResultsAmong the 1 504 newborns， gestational age at birth was lower in MCDA group compared with DCDA group （P = 0.000）， and the degree of birth weight discordance was higher in MCDA group than that of the DCDA group （P = 0.001）. Birth asphyxia， respiratory distress syndrome （RDS）， bronchopulmonary dysplasia （BPD）， and sepsis were more frequency in MCDA group compared with DCDA group （P = 0.000， P = 0.000， P = 0.000， P = 0.000）. Low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis， necrotizing enterocolitis （NEC）≥stageⅡ， acute kidney injury （AKI）， retinopathy of prematurity （ROP）， and neonatal death respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.011， P = 0.000， P = 0.000， P = 0.000）. High degree of birth weight discordance was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP respectively （P = 0.045， P = 0.000， P = 0.000， P = 0.004， P = 0.017 ）. Chorionicity was not an independent risk factor for neonatal morbidity and death （P > 0.05）. Among the 168 twins with birth weight discordance ≥25%， low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP， respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.000）； small twin was an independent risk factor for birth asphyxia and BPD， respectively （ P = 0.013， P = 0.001）； chorionicity was not an independent risk factor for neonatal morbidity （P > 0.05）. ConclusionChorionicity was not an independent risk factor for adverse neonatal outcome in twin births. Low gestational age at birth and high degree of birth weight discordance were independent risk factor for adverse neonatal outcome in twin births. Small twins had increased risk of adverse neonatal outcome in twins with birth weight discordance ≥25%.

Objective:To investigate the application value and effect of surgical removal and setons abscess drainage in moderate and severe acne inverse.Methods:A retrospective case study of 4 patients (3 males and 1 female with an average of onset of 28 years) with acne inverse at gluteal and perianal area in the Qixia Traditioal Chinese Medical Hospital of Shandong province between June 2016 and August 2020, The operative technique was based on the complete excision of the entire diseased skin and subcutaneous fatty tissue, down to the muscular fascia. The cavity was explored using a probe, two setons were placed in each of the fistula tracts, and the wound were covered with absorptive dressing.Results:All the wounds in 4 patients healed primarily and showed no recurrence after surgery, execpt for one patient who did not take supine position in time after operation which resulted in more bleeding in a short time. The other patients recovered well. The patients were followed up for 6 months without affecting the anal skin function, skin lesions and recurrence.Conclusions:The technique of wide surgical excision and setons abscess drainage is an effective method for moderate and severe acne inverse.

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.
Antineoplastic Agents/pharmacology* ; Asclepias/chemistry* ; Cardenolides/pharmacology* ; Glycosides/pharmacology* ; Humans ; Seeds

ObjectiveThe aspartate aminotransferase-to-platelet ratio index （APRI） and liver fibrosis-4 index （FIB-4） have been used for noninvasive prediction of liver fibrosis and cirrhosis and both indexes exhibit a high degree of accuracy in the the prediction of the prognosis of hepatocellular carcinoma（HCC）patients after hepatectomy.. This study aims to explore the predictive values of APRI and FIB-4 in the occurrence of posthepatectomy liver failure （PHLF） in HCC patients. MethodsThe clinical data of 426 patients with HCC who underwent hepatectomy in our hospital were retrospectively analyzed. Laboratory data were collected from patients within 2 weeks prior to hepatectomy. APRI， FIB-4 and Child-Pugh scores were calculated. Receiver operating characteristic （ROC） curves were used to determine the AUC values and optimal cut-off values of APRI， FIB-4 and Child-Pugh scores. Univariate and multivariate logistic regression analyses were employed to identify the independent risk factors for PHLF， and the predictive values of APRI and FIB-4 on PHLF were compared. ResultsA total of 48 patients （11.3%） developed PHLF. Multivariate analysis showed that major hepatectomy （≥3 segments resection）， blood loss >400 mL， total bilirubin （TBIL）， platelet （PLT）， fibrinogen （Fib）， APRI and FIB-4 were independent risk factors for PHLF. ROC curve analysis revealed that APRI （AUC = 0.816） and FIB-4 （AUC = 0.728） had better ability to predict PHLF than Child-Pugh score （AUC = 0.566； P<0.001）. ConclusionsPreoperative APRI and FIB-4 are independent predictors of PHLF in HCC patients after hepatectomy and have good predictive values.

ObjectiveThe purpose of this study was to analyze the correlation between SUVmax on primary prostate lesion of two-phase ⁶⁸Ga-PSMA-11 PET/CT and the clinicopathological features of patients with preliminary diagnosis of prostate cancer. MethodsPET/CT images of 19 patients with prostate cancer first diagnosed in our hospital from November 2017 to September 2020， aged 69.0±7.4 years， were collected. All patients underwent ⁶⁸Ga-PSMA-11 PET/CT dual-phase examination， and radical resection of prostate cancer was performed within two weeks. Semi-quantitative parameters of ⁶⁸Ga-PSMA-11 PET/CT on primary prostate cancer， SUVmax1 in the standard phase imaging， SUVmax2 in the delayed phase imaging and SUVmax3 （difference between SUVmax2 and SUVmax1）， were measured by automatic segmentation algorithm method. Clinical and pathological data of each patient were collected. Mann-Whitney U test and ROC curve analysis were used to compare SUVmax and the clinicopathological characteristics of patients in two independent samples. P<0.05 was considered as statistically significant difference. ResultsThe differences of SUVmax1， SUVmax2 and SUVmax3 between GS≤7 group and >7 group were statistically significant（P＜0.05）， and the areas under the ROC curves were 0.845， 0.845 and 0.893， respectively. SUVmax1， SUVmax2 and SUVmax3 were significantly different between ISUP grade ≤2 group and >2 group （P<0.05）， and the areas under the ROC curve were 0.773， 0.784 and 0.852， respectively. The difference of SUVmax3 between T stage ≤T2 group and >T2 group was statistically significant （P<0.05）， while the difference of SUVmax1 and SUVmax2 between T stage ≤T2 group and >T2 group was not statistically significant （P>0.05）. The difference of SUVmax3 between D’ Amico low-medium-risk group and high-risk group was statistically significant （P<0.05）， while the difference of SUVmax1 and SUVmax2 between D’ Amico low-medium-risk group and high-risk group was not statistically significant （P>0.05）. There was no significant difference in SUVmax1， SUVmax2 and SUVmax3 between total PSA ≤20 ng/mL group and >20 ng/mL group （P>0.05）. SUVmax1， SUVmax2 and SUVmax3 were significantly different between positive nerve invasion group and negative group （P<0.05）， and the areas under the ROC curves were 0.872， 0.923 and 0.974， respectively. ConclusionsSUVmax2 and SUVmax3 were positively correlated with multiple clinical and pathological features of prostate cancer. Compared with standard phase imaging， dual-phase imaging of ⁶⁸Ga-PSMA-11 PET/CT may provide more favorable value in predicting the clinical and pathological features of prostate cancer patients before surgery.

ObjectiveThe aspartate aminotransferase-to-platelet ratio index （APRI） and liver fibrosis-4 index （FIB-4） have been used for noninvasive prediction of liver fibrosis and cirrhosis and both indexes exhibit a high degree of accuracy in the the prediction of the prognosis of hepatocellular carcinoma（HCC）patients after hepatectomy.. This study aims to explore the predictive values of APRI and FIB-4 in the occurrence of posthepatectomy liver failure （PHLF） in HCC patients. MethodsThe clinical data of 426 patients with HCC who underwent hepatectomy in our hospital were retrospectively analyzed. Laboratory data were collected from patients within 2 weeks prior to hepatectomy. APRI， FIB-4 and Child-Pugh scores were calculated. Receiver operating characteristic （ROC） curves were used to determine the AUC values and optimal cut-off values of APRI， FIB-4 and Child-Pugh scores. Univariate and multivariate logistic regression analyses were employed to identify the independent risk factors for PHLF， and the predictive values of APRI and FIB-4 on PHLF were compared. ResultsA total of 48 patients （11.3%） developed PHLF. Multivariate analysis showed that major hepatectomy （≥3 segments resection）， blood loss >400 mL， total bilirubin （TBIL）， platelet （PLT）， fibrinogen （Fib）， APRI and FIB-4 were independent risk factors for PHLF. ROC curve analysis revealed that APRI （AUC = 0.816） and FIB-4 （AUC = 0.728） had better ability to predict PHLF than Child-Pugh score （AUC = 0.566； P<0.001）. ConclusionsPreoperative APRI and FIB-4 are independent predictors of PHLF in HCC patients after hepatectomy and have good predictive values.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*