OBJECTIVE To analyze the influential factors for potentially inappropriate medication （PIM） in elderly cancer patients. METHODS The data of elderly cancer patients hospitalized in a hospital from January to December 2021 were collected. According to the Beers standard of the American Geriatrics Society in 2019 （hereinafter referred to as the “2019 version of Beers standard”） and Criteria for Potentially Inappropriate Drug Use in Chinese Elderly （2017 version） （hereinafter referred to as the “Chinese PIM standard”）， the PIM status of elderly cancer patients was retrospectively analyzed. Multivariate Logistic regression analysis was used to identify influential factors for PIM. RESULTS A total of 293 patients were included in the study. According to the 2019 version of Beers standard， 211 patients （72.01%） had PIM， of which 204 （69.62%） had PIM related to drugs， 6 （2.05%） had PIM related to diseases or symptoms， 46 （15.70%） had PIM that should be used with caution， 32 （10.92%） had PIM with drug-drug interaction that should be avoided， and 11 （3.75%） had PIM based on renal function； the top 5 drugs in the list of incidence were proton pump inhibitors， metoclopramide， the first-generation antihistamines as promethazine， analgesics as ibuprofen and megestrol. According to the Chinese PIM standard， there were 132 patients （45.05%） with PIM， of which 119 （40.61%） had PIM related to drugs， involving 25 drugs （included 7 high-risk drugs and 18 low-risk drugs）， and 24 （8.19%） with PIM in disease status； top 4 drugs in the list of incidence were promethazine， megestrol， ibuprofen and cimetidine. Multivariate Logistic regression analysis showed that compared with patients with hospital stay≤10 days， patients with hospital 20054） stay between 11 and 30 days had a higher risk of PIM [odds ratio （OR）＝8.836 8， 95% confidence interval （CI） （3.217 8， 31.940 9）， P＝0.000 1]； compared with the patients with the 65895198。E-mail：fjman@cmpt.ac.cn number of clinical disease diagnosed≤5， patients with the number of clinical disease diagnosed≥11 had a higher risk of PIM [OR＝10.930 1， 95%CI （3.000 9， 70.922 9）， P＝0.001 8]； compared with surgical treatment， patients receiving antineoplastic drugs had a higher risk of PIM [OR＝2.209 5， 95%CI （1.180 2， 4.176 9）， P＝0.013 6]. CONCLUSIONS Elderly cancer patients have multiple diseases， complicated medication， and a high incidence of PIM. The length of hospital stay （11-30 d）， the number of clinical disease diagnosed （≥11） and anti-tumor drugs are main influential factors for PIM in patients.

Objective : To investigate the impact of dexmedetomidine on the oncological behavior of hepatocellular carcinoma and explore the role of NF-E2-related factor 2 (Nrf2) at both in vitro and in vivo levels． Methods : In vivo experiment，Male C57BL/6J mice were randomly divided into a control group ( Ctrl group) ，a hepatocellular carcinoma group ( HCC group) ，and a hepatocellular carcinoma + dexmedetomidine group ( HCC + Dex group) . Hepatocellular carcinoma was induced in mice by combining N-Nitrosodiethylamine ( DEN) / carbon tetrachloride ( CCl4 ) ，followed by daily intraperitoneal injection of 10% dexmedetomidine for two weeks．After feeding the mice for one month，the mice were assessed for the quantity and size of liver tumors．The proliferation ability of liver cancer was evaluated using Ki67 immunohistochemistry．Additionally，the expression level of Nrf2 protein in tumor tissue was measured through immunofluorescence．In vitro experiment，Hepa1-6 cells were incubated with different concentrations of dexmedetomidine (0. 1，1，5 nmol /L) for 48 hours to examine their effects．The proliferation， migration and invasion abilities of Hepa1-6 cells were evaluated using the MTT and Transwell methods．The expres- sion level of Nrf2 protein in the Hepa1-6 cells was measured using Western blot and immunofluorescence．Addition- ally，the proliferation ，migration and invasion abilities of cells were assessed after Nrf2 knockdown via si-RNA transfection，in combination with incubation with 1 nmol /L dexmedetomidine for 48 hours. Results : ompared to the HCC group，the anatomical examination results revealed an increase in the number of liver tumors and the lon- gest diameter in the HCC + Dex group (P ＜0. 05) ． Ki67 immunohistochemistry results indicated the number of Ki67 positive cells in liver cancer tissue increased in the HCC + Dex group (P＜0. 01) ．The immunofluorescence assay demonstrated an upregulation of Nrf2 expression level in the HCC + Dex group (P ＜0. 05 ) ． MTT results showed that 1 nmol /L of dexmedetomidine increased the cell viability of Hepa1-6 cells (P＜0. 05) ．Transwell re- sults indicated that 0. 1 ，1 ，and 5 nmol /L of dexmedetomidine enhanced the invasive ability of Hepa1-6 cells， while 0. 1 and 1 nmol /L of dexmedetomidine enhanced the migration ability (P＜0. 05) ．Western blot and immu- nofluorescence results showed an upregulation of Nrf2 expression level in cells after treatment with 1 nmol /L dexme- detomidine (P＜0. 01) ．The Nrf2 expression level of cells was reduced using si-RNA，followed by treatment with 1 nmol /L dexmedetomidine．The results from MTT and Transwell assays revealed a decrease in the viability，invasion and migration ability of Hepa1-6 cells (P＜0. 01) ． Conclusion Dexmedetomidine may enhance the proliferation， invasion and migration capacity of hepatocellular carcinoma by upregulating the expression of Nrf2 .

Objective : High performance liquid chromatography⁃mass spectrometry (LC⁃MS/MS) system was used to accurately determine 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice , and a LC⁃MS/ MS method was established for efficient detection and analysis of bile acids in serum , liver, amniotic fluid and placenta of mice. Methods : Pregnant mice serum , liver, amniotic fluid and placenta samples were processed , with 0. 1% glacial acetic acid in 4 mmol/L ammonium acetate aqueous solution as mobile phase A and pure methanol as mobile phase B , the flow rate was 0. 4 ml/min , a gradient elution program was used to elute with Phenomenex Gemini 3 μm NX⁃C18 110A ( 100 mm × 2. 0 mm) chromatographic column elution , and mass spectrometry detection system used an electrospray ion source for negative ion multiple reaction monitoring. Results : The linear relationship of 22 bile acids in the quantitative range was good. The RSD of inter⁃day and intra⁃day precision at low , medium and high concentrations was 0. 5% - 7. 4% , the matrix effect was 88% - 110% , and the extraction recovery was 84% - 108% . Conclusion In this experiment , LC⁃MS/MS was established to detect 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice. The method not only has high sensitivity and selectivity , but also can stably detect a large number of samples.

Cardiovascular disease is the leading cause of death in China. Due to its great individual differences in genetic background, pathogenesis and disease development trend, the survival risk rate after standardized western medicine treatment under the guidance of the current guidelines remains high. Traditional Chinese medicine(TCM) has unique multiple-target, multiple-pathway and multiple-layer advantages, which can effectively make up for shortcomings of western medicine. Therefore, it has been widely used in the treatment of cardiovascular diseases. Oxidative stress is one of the important causes of cardiovascular diseases. Nuclear factor erythroid-2-related factor 2(Nrf2) is the central regulator of this reaction. When being activated, it can transfer to the nucleus and initiate signaling in the downstream pathway, thus playing an anti-oxidative stress role. As one of the most important endogenous protection systems in the body, the Nrf2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway is the most classical approach for Nrf2 in playing roles. There have been certain achievements in studying and clarifying TCM by regulating this pathway to treat cardiovascular diseases using modern molecular biology and other methods. Based on this, this paper summarized the relationship between Nrf2/HO-1 signaling pathway and cardiovascular diseases, then concluded and analyzed the mechanism and pharmacological effects of TCM and its active ingredients in Nrf2/HO-1 signaling pathway on different cardiovascular diseases, involving active ingredients of TCM, TCM pairs active ingredients, TCM extracts and TCM formula. This paper provides a theoretical reference for the development and utilization of anti-cardiovascular drugs.

Objective To investigate the effect of pericapsular nerve group(PENG)block with wound infiltration(WI)on postoperative analgesia after total hip arthroplasty(THA).Methods A total of seventy-eight patients who were scheduled to undergo THA in the Third Affiliated Hospital of Anhui Medical University from December 2021 to October 2022 were selected.According to random number table method,they were divided into PENG block group and PENG block +WI group,39 cases in each group.Numerical rating scale(NRS)score of postoperative rest and exercise,incidence of postoperative movement block,first walking time,incidence of rescue analgesia and adverse reactions were compared between two groups.Results At 6h and 12h after surgery,NRS scores at rest in PENG block +WI group were significantly lower than those in PENG block group(P<0.05),and at 6h,12h and 24h after surgery,NRS scores at exercise in PENG block +WI group were significantly lower than those in PENG block group(P<0.05).The first walking time of patients in PENG block +WI group was significantly shorter than that in PENG block group[(22.48±4.00)h vs.(24.73±1.94)h,t=3.150,P=0.003].There were no significant differences in incidence of rescue analgesia,movement block at different time points,nausea and vomiting,and postoperative agitation between two groups(P>0.05).Conclusion PENG block +WI can reduce the postoperative pain of THA patients,and is conducive to early activity,which is in line with the concept of enhanced recovery after surgery.

To study the effect of Huangqin Qingre Chubi Capsules containing serum on the protein expressions of AMPK and FoxO3 a in peripheral blood mononuclear cells of patients with rheumatoid arthritis(RA), in order to explore the mechanism of anti-oxidation. Peripheral anticoagulant was collected from patients and normal people. Monocytes(PBMC) were isolated through density gradient centrifugation, and the logarithmic phase cells were cultured. Drug containing serum was prepared through intragastric admini-stration to SD rats. The rats were divided into five groups, namely normal group, model group, AMPK blocker group(compound C 10 μmol·L~(-1)), medium-dose HQC+AMPK blocker group, and middle-dose HQC group. The cell inhibition rate was calculated by MTT method. The levels of IL-1β, IL-4, LPO, MDA, SOD and TAOC were detected by ELISA. The expressions of AMPK, p-AMPK, p-FoxO3 a and FoxO3 a were detected by Western blot. The HQC containing serum had an inhibitory effect on human monocytes in peripheral blood. The best concentration was observed in middle-dose HQC, and the best time was 24 hours. Middle-dose HQC group was better than model group, AMPK blocker group and middle-dose HQC + AMPK blocker group in terms of increase of SOD, p-AMPK, p-FoxO3 a and decrease of LPO. It was better than model group and AMPK blocker group in terms of increase of IL-4, TAOC, AMPK, FoxO3 a and decrease of IL-1β, MDA. The differences were statistically significant(P<0.05 or P<0.01). The HQC containing serum may increase the levels of TAOC and SOD, decrease the level of MDA and LPO, activate AMPK, directly phosphorylate FOXO3 a, enhance its transcriptional activity, and improve the state of oxidative stress in RA patients.
AMP-Activated Protein Kinases ; Animals ; Arthritis, Rheumatoid ; Capsules ; Forkhead Box Protein O3 ; Humans ; Leukocytes, Mononuclear ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Scutellaria baicalensis

ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg^-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg^-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E₂ （PGE₂） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE₂ contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.

ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β₁-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L^-1 TGF-β₁. MGC-803 cells were classified into blank group， model group， 0.1 g·L^-1 XXXT group， 0.2 g·L^-1 XXXT group， and 0.4 g·L^-1 XXXT group. For further clarifying the key role of Wnt5a/Ca²⁺/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L^-1） group， and Wnt5a-OE + XXXT （0.4 g·L^-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca²⁺/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca²⁺ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca²⁺/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L^-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca²⁺ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca²⁺/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β₁. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer cells.

OBJECTIVE To investigate the effects of 0.2% chloroprocaine combined with ropivacaine on epidural labor analgesia and median effective concentration （EC50） of ropivacaine. METHODS Totally 67 parturients who scheduled for vaginal delivery and required epidural labor analgesia were collected from our hospital from July to October 2023 and randomly divided into RL group （33 cases） and R group （34 cases）. The concentration of ropivacaine was determined by modified Dixon sequential method. RL group was given 0.2% Chloroprocaine hydrochloride injection+Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection； R group was given Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection. EC50 of ropivacaine， analgesic effect during delivery， total dosage of analgesic drugs， analgesic satisfaction score， the incidence of adverse reactions， delivery status， and Apgar score of newborns were observed in two groups. RESULTS EC50 of ropivacaine， onset time， remedial analgesia rate， the incidence of perineal distension and breakthrough pain and total dosage of analgesic drugs of RL group were significantly lower than R group， and analgesic satisfaction score was significantly higher than R group （P＜0.05）. There was no statistical significance in the incidence of adverse reactions such as numbness， weakness， and chills in the lower limbs， or the duration of labor， amount of bleeding， mode of delivery， and Apgar score of newborns between 2 groups （P＞0.05）. CONCLUSIONS For epidural labor analgesia， 0.2% chloroprocaine combined with ropivacaine can reduce EC50 of ropivacaine， improve analgesia effect and have good safety.

Objective:This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-β₁（TGF-β₁），and to explore the mechanism of regulating Wnt5a/Ca²⁺/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells. Method:TGF-β₁（10 μg·L^-1）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca²⁺/NFAT signaling pathway， and intracellular Ca²⁺ concentration. Result:Compared with the blank group， TGF-β₁ could significantly enhance the invasion and migration ability of MGC-803 cells（P<0.01）， down-regulate the level of E-cadherin（P<0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（P<0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca²⁺（P<0.01）. Compared with the TGF-β₁ group， modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） could significantly inhibit this phenomenon，and 40 mg·L^-1 had the best effect（P<0.05，P<0.01）.The specific inhibitors of Wnt5a/Ca²⁺/NFAT signaling pathway （R）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L^-1） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-β₁， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca²⁺（P<0.05，P<0.01）.Moreover， （R）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L^-1） had stronger inhibitory effect（P<0.05，P<0.01）. Conclusion:These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-β₁ via Wnt5a/Ca²⁺/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.