ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective:To evaluate the efficacy of robot-assisted Y-V plasty (RAYV) and laparoscopic Y-V plasty (LYV) in the treatment of refractory bladder neck contracture (BNC) after BPH surgery.Methods:A retrospective analysis was performed for the clinical data of 42 patients with refractory BNC after BPH surgery from January 2020 to July 2023, including 18 RAYV and 24 LYV. There were no significant differences between both groups( P>0.05) in term of median age [68(62, 81) years vs. 70(61, 76) years], median body mass index [20.7(17.6, 26.1) kg/m 2 vs. 19.8(16.3, 25.3) kg/m 2], median Q max [9.4(5.6, 13.2) ml/s vs. 8.9(6.2, 12.2)ml/s], median IPSS [20.5(15, 23) vs. 21.1(17, 23)], median QOL score [4.6 (4, 6) points vs. 4.8 (4, 6) points] and median postvoid residual volume [84.7(58, 125)ml vs. 78.3(50, 120)ml]. Preoperative examination of one patient in the RAYV group showed no contractile function of the external urethral sphincter.The surgical procedure was basically the same for both groups: entering into the retropubic space, and incision of the anterior wall of bladder and prostate urethra was performed in an inverted Y-shaped. After excising the scar around the anterior wall of bladder neck, the apex of inverted V-shaped bladder wall flap is brought to the base of the Y-shaped incision using two 3-0 running suture. The catheter was removed 2 weeks after surgery. Perioperative and follow-up data were compared between the two groups. Results:All surgeries were successfully completed without complications. The difference between RAYV and the LYV group in operation time [71.8(50, 98)min vs. 105.9(71, 143)min] and postoperative drainage removal time [2.7(2, 4)d vs. 4.5(3, 7)d] was statistically significant ( P<0.05). There was no significant difference between both groups in term of intraoperative blood loss [50.4(20, 100) ml vs. 60.8(40, 150) ml] and postoperative hospital stay [4.1(3, 5)d vs. 4.6(3, 7)d]( P>0.05). All patients were followed up with a median follow-up of 16.5(2, 41) months. There was no significant difference between RAYV and LYV in term of postoperative Q max [27.9(11.7, 37.6) ml/s vs. 22.4(12.3, 31.5)ml/s], IPSS[5.1(4, 9) points vs. 4.8(4, 10) points], QOL[1.6(1, 3) points vs. 1.5(1, 3) points] and postvoid residual volume [5.6(0, 15) ml vs. 7.2(5, 20) ml] ( P>0.05). The postoperative bladder neck patency rates in the RAYV group and the LYV group were 94.4%(17/18) and 95.8%(23/24), respectively, with no significant difference( P>0.05). In terms of urinary continence, 1 patient in the RAYV group had no contractile function of the external urethral sphincter before surgery, and none of the 41 patients with good preoperative continence had urinary incontinence after surgery. Conclusions:The effect of RAYV in the treatment of refractory BNC after BPH surgery is comparable to that of LYV, but RAYV can shorten the operation time and postoperative drainage time.

Ureteral stenosis and bladder contracture after radiotherapy for cervical cancer are challenging issues in urology. Ileal ureteroplasty combined with ileal bladder augmentation is a potential method to improve hydronephrosis and voiding function of patients, however, the surgical procedure is complex, with high surgical risks and numerous intraoperative and postoperative complications, which have hindered the widespread application of this surgical technique. This article introduces our hospital's experience through a typical surgical case. During the surgery, ileal substitution for bilateral ureters was performed in combination with ileal " N-shaped" augmentation. Two weeks after the surgery, the single-J stent was removed, and the urinary catheter was removed three weeks after the surgery. The patient achieved voluntary urination control with smooth voiding. Follow-up examinations at 3 months and 18 months postoperatively showed no hydronephrosis in the bilateral ureters, normal renal function, and a significantly expanded bladder capacity.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

AIM:To investigate the impact and regulatory mechanisms of zinc finger protein 36-like protein 1(ZFP36L1)on pancreatic carcinoma cell growth.METHODS:The ZFP36L1 expression in pancreatic carcinoma and its correlation with patient prognosis were analyzed using online databases UALCAN and GEPIA.Western blot was utilized to detect ZFP36L1 protein expression in pancreatic ductal cells(HPNE)and three different pancreatic carcinoma cell lines.CCK-8 and cell colony formation assays were performed to evaluate the effects of ZFP36L1 on pancreatic cancer cell prolif-eration.Wound healing and Transwell assays were used to assess the impact of ZFP36L1 expression changes on pancreatic carcinoma cell migration and invasion.Flow cytometry experiments were used to analyze the effect of ZFP36L1 on the pan-creatic carcinoma cell cycle process.Bioinformatics analysis was conducted to predict potential ZFP36L1 interacting pro-teins.Co-immunoprecipitation experiments were carried out to confirm the interaction between ZFP36L1 and mitogen-acti-vated protein kinase 14(MAPK14).Rescue experiments were performed to assess the function of MAPK14 in ZFP36L1-regulated pancreatic carcinoma cell growth.RESULTS:(1)ZFP36L1 is highly expressed in pancreatic carcinoma and is positively correlated with poor prognosis in pancreatic carcinoma patients.Compared to HPNE,ZFP36L1 is highly ex-pressed in MIA PaCa-2 and ASPC-1 cells,but relatively low in PANC-1 cells.(2)ZFP36L1 overexpression significantly increased the cell viability,colony formation,migration,and invasion abilities of PANC-1 and MIA PaCa-2 cells,while siRNA interference of ZFP36L1 led to opposite results.(3)ZFP36L1 promotes the entry of pancreatic carcinoma cells into the S phase of the cell cycle.(4)ZFP36L1 interacts with MAPK14 to regulate pancreatic cancer cell growth.MAPK14 overexpression reversed the cell viability and migration abilities of pancreatic carcinoma cells overexpressing ZFP36L1.Furthermore,it also decreased the cell viability and migration abilities of pancreatic carcinoma cells with ZFP36L1 inter-ference.CONCLUSION:ZFP36L1 is a potential oncogene in pancreatic carcinoma growth and may regulate pancreatic carcinoma cell growth through cell cycle modulation and interaction with MAPK14.

Objective:To study the changing trend of brucellosis epidemic in Taiyuan City, Shanxi Province from 2004 to 2022, and to provide reference for formulating brucellosis prevention and control policies.Methods:Through the China Disease Prevention and Control Information System, the epidemic data of human brucellosis with the onset time from January 1, 2004 to December 31, 2022 and the current address in Taiyuan City were collected. Descriptive epidemiological methods were used to analyze the temporal, regional, and population distribution characteristics of brucellosis.Results:From 2004 to 2022, a total of 1 834 cases of brucellosis were reported in Taiyuan City, with an average annual incidence rate of 2.25/100 000. The incidence rate of brucellosis in each year showed a fluctuating upward trend (χ 2trend = 428.04, P < 0.001). The onset time was mainly concentrated from February to August, accounting for 76.94% (1 411/1 834) of the total cases, with May being the peak month (283 cases). The incidence rate of brucellosis in all counties (cities and districts) ranged from 0 to 38.37/100 000, with the highest incidence rate in Loufan County in 2021. There were 1 470 males and 364 females, with a male-to-female ratio of 4.04 ∶ 1.00. The age range was 1 to 95 years old, among which the 1 - 29 age group accounted for 14.29% (262/1 834), the 30 - 39 age group accounted for 13.14% (241/1 834), the 40 - 49 age group accounted for 21.05% (386/1 834), the 50 - 59 age group accounted for 27.54% (505/1 834), and the 60 - 95 age group accounted for 23.99% (440/1 834). The main occupation was farmers and herdsmen, accounting for 67.23% (1 233/1 834). Conclusion:From 2004 to 2022, the epidemic of brucellosis in Taiyuan City shows a fluctuating upward trend, with males, middle-aged and elderly people, and farmers and herdsmen as the main affected population.

Objective:To explore the impact of artificial intelligence compressed sensing technology (CS-AI) on image quality in three-dimensional proton density weighted imaging (3D PDWI) of the unilateral hip joint.Methods:High-resolution unilateral hip imaging was conducted on 67 healthy volunteers at West China Hospital of Sichuan University from January to July 2023. Imaging was performed by using CS-AI 3D PDWI sequence with acceleration factors (AF) of 4, 6, 8, and 10, respectively. According to the AF, all subjects were divided into 4 groups: CS-AI 4, CS-AI 6, CS-AI 8 and CS-AI 10, with CS-AI 4 serving as a reference. Recording the scan time, the signal and noise intensity of the femoral head, muscle, and subcutaneous fat were measured by a senior radiologist and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were then calculated. Additionally, two observers provided ratings for overall image quality and artifacts in the 4 groups, and statistical analysis was performed using the Friedman rank-sum test.Results:The acquisition times for CS-AI 4, CS-AI 6, CS-AI 8, and CS-AI 10 were 5 min 49 s, 3 min 54 s, 2 min 56 s and 2 min 22 s, respectively. Compared to CS-AI 4, the scanning time for CS-AI 6, CS-AI 8, CS-AI 10 were reduced by 32.95%, 50.14%, 59.31%, respectively. The objective evaluation revealed that the SNR and CNR of the femoral head and muscle in groups CS-AI 6, CS-AI 8, and CS-AI 10 were slightly lower than those in group CS-AI 4 ( P<0.05), and the differences were statistically significant. However, no statistically significant differences were found among the 3 groups ( P>0.05). The subjective evaluation indicated that the overall image quality scores of group CS-AI 8 [3 (3,4)] did not significantly differ from those of group CS-AI 4 and CS-AI 6( P>0.05); The mean scores of group CS-AI 4 and CS-AI 6 were 4 (4, 4); Scores of group CS-AI 10 was 3(3, 3), which statistically significant differ from those of the other groups ( P<0.05). The artifacts rating for groups CS-AI 4, CS-AI 6, CS-AI 8 and CS-AI 10 were 4 (4, 4), 4 (4, 4), 3 (3, 4), and 2 (2, 3) respectively. When AF was set to 10, the images exhibited the most severe artifacts ( P<0.05). For other AF values, artifact ratings did not differ significantly ( P>0.05). Conclusion:The CS-AI 3D-PDWI sequence with acceleration factor 8 can acquire high-resolution images of the unilateral hip joint that meet clinical diagnostic requirements while reducing scanning time.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200～220 g)were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCαinhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8)and propofol+gap junction inhibitor metoclopramide sodium(Movens)group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE)and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42％in the superior mesenteric artery(SMA,P＜0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57％(P＜0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95％and 88.63％(P＜0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79％and 169.90％(P＜0.05),separately,while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups.Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats,which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.