[摘 要] 目的：探究错配修复蛋白2（MSH2）在胃癌中表达和其与患者临床特征的关系及其对胃癌细胞恶性生物学行为的作用及机制。方法：收集2020年5月至2022年7月期间在邢台市人民医院收治的40例胃癌患者的癌组织和配对癌旁组织及患者的一般临床资料。常规培养正常人胃黏膜上皮细胞GES-1和胃癌细胞AGS、MKN45和BGC-823，用转染试剂分别将sh-NC、shMSH2-1和shMSH2-2慢病毒载体转染至AGS和MKN45细胞中，实验分为sh-NC、shMSH2-1和shMSH2-2组。CCK-8法、克隆形成实验、EdU染色、Transwell小室实验分别检测各组AGS和MKN45细胞的增殖、迁移和侵袭能力。构建裸鼠MKN45细胞移植瘤模型，观察敲减MSH2对移植瘤生长的影响。WB法检测各组细胞中及移植瘤组织中 MSH2、PI3K/AKT/mTOR通路、上皮间质转化相关蛋白的表达。结果：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良均有关联（均P < 0.001）；在AGS和MKN45细胞中成功地敲减了MSH2的表达（P < 0.001）；敲减 MSH2均能显著抑制AGS和MKN45细胞的活力、EdU染色阳性率、克隆形成能力、迁移及侵袭能力和移植瘤的生长（均P < 0.001）；均能显著抑制AGS和MKN45细胞和MKN45移植瘤组织中MSH2蛋白、PI3K/AKT/mTOR通路相关蛋白、N-cadherin蛋白的表达（均P < 0.001），促进E-cadherin蛋白的表达（P < 0.001）。结论：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良有关联，敲减MSH2表达通过抑制PI3K/AKT/mTOR通路调控AGS和MKN45细胞的恶性生物学行为，MSH2可能是胃癌治疗的潜在靶点。

AIM: To evaluate the effect of capsular tension ring(CTR)on the stability and accuracy of Barrett universal Ⅱ intraocular lens(IOL)calculation formula in patients with high myopia and cataract.METHODS:Prospective study. A total of 40 cases(80 eyes)of high myopia and cataract that visited our hospital from January to June 2022 were selected. The patients were divided into CTR group and blank group by random number table method, with 40 eyes in each group. All patients were measured by IOL Master, and the actual implanted IOL power and predicted postoperative power were calculated according to Barrett universal Ⅱ formula. The uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA)at 6 mo after surgery were recorded, and the mean absolute error(MAE)was compared at 6 mo after surgery. Furthermore, the stability of postoperative refractive status and the relationship between the predicted postoperative diopter and CTR were evaluated.RESULTS:The UCVA and BCVA of the two groups were improved at 6 mo after operation(P>0.05), and there was no significant difference in UCVA and BCVA between the two groups at each time point(all P>0.05). After the implantation of IOL in 80 eyes based on the Barrett universal Ⅱ formula, the predicted postoperative diopter was -2.01±0.71 D, the actual postoperative diopter was -1.64±0.88 D, and the MAE was 0.37±0.98 D in the CTR group; in the blank group, the predicted diopter was -2.12±0.64 D, the actual diopter was -1.54±0.88 D, and the MAE was 0.58±0.31 D. The difference between the two groups was statistically significant(P<0.05). According to the axial length, CTR implantation can effectively reduce refractive error for any axial length(P>0.05). With the grouth of axial length, the MAE value increased. The postoperative MAE value of patients with axial length ≥30 mm was statistically different between the two groups(P<0.05).The proportion of hyperopic drift was 18%(7/40)in the CTR group and 30%(12/40)in the blank group, respectively, with a significant difference between the two groups(P<0.05).CONCLUSION: For patients with high myopia and cataract, the Barrett universal Ⅱ formula has high accuracy in predicting postoperative diopter. Intraoperative implantation of CTR can not only maintain the shape of the capsule bag, effectively prevent the intraoperative rupture of the suspensory ligament of the lens and make the IOL more neutral, but also is conducive to the early stability of postoperative diopter of cataract patients. It also provides more stable refractive results and reduces refractive drift. For myopic patients considering CTR implantation, it is recommended to increase the preoperative reserve diopter of -0.50 D to achieve the ideal refractive state.

OBJECTIVE To investigate the protective effect and mechanism of quercetin on the cardiac and renal functions of rats with cardiorenal syndrome （CRS） based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa- B （NF-κB） signaling pathway. METHODS CRS model of SD rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion. Model rats were randomly separated into model group， quercetin low-dose group （35 mg/kg）， quercetin high-dose group （70 mg/kg）， high-dose of quercetin+740Y-P group （70 mg/kg quercetin+3.5 mg/kg PI3K/Akt/ NF-κB signaling pathway activator 740Y-P）， with 12 rats in each group. Another 12 normal rats were selected as sham operation group. They were given relevant drugs， once a day， for 14 consecutive days. After administration， the cardiac function indexes [left ventricular ejection fraction （LVEF）， end-diastolic volume （EDV）， isovolumic relaxation time （IVRT）] and renal function indicators [blood urea nitrogen （BUN）， 24-hour urine protein， and serum creatinine （Scr）] were detected， and fibrosis in the cardiac and renal tissues was observed； the levels of inflammatory indexes [interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）] in the serum and cardiac and renal tissues as well as the expression of PI3K/Akt/NF-κB pathway-related proteins in the cardiac and renal tissues were detected. RESULTS Compared with sham operation group， the levels of BUN， 24-hour urine protein and Scr， collagen volume fraction of cardiac and renal tissues， the levels of IL-1β and TNF-α in serum and cardiac and renal tissues， and the phosphorylation of PI3K， Akt and NF-κB p65 protein in cardiac and renal tissues were increased significantly in model group （P＜0.05）； the levels of LVEF， IVRT and EDV were reduced significantly （P＜0.05）. Compared with the model group， the above indexes were reversed significantly in quercetin low-dose and high-dose groups （P＜0.05）， and the reversal effect was better in the high-dose group （P＜0.05）. 740Y-P restored the reverse effect of high-dose quercetin on the indexes （P＜0.05）. CONCLUSIONS Quercetin can alleviate cardiac and renal fibrosis and function injury， the mechanism of which may be 20232016） associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.

Objective To investigate the effects of fentanyl citrate on pain in aged rats with hip fracture and its underlying mechanisms. Methods Thirty aged rats with hip fracture were divided into model group (n=10), fentanyl citrate group (n=10), and fentanyl citrate + Sar-SP group (n=10). Additionally, healthy rats from the same period were included as normal group (n=10).Rats in the fentanyl citrate group received intravenous tail injection of 10 μg/kg fentanyl citrate, while those in the fentanyl citrate + Sar-SP group underwent intrathecal injection of 10 μL Sar-SP for fentanyl citrate intervention. Rats in the normal and model groups received intravenous tail injection of an equal volume of saline. Pain threshold, weight-bearing capacity, temperature, and dorsoventral thickness of the hind paws were measured before treatment (0 h) and at 1, 6, 24, and 168 h post-treatment. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and glutamic acid (Glu) in the spinal cord tissue of rats. Immunohistochemical staining was employed to observe the positive expression rates of ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), and substance P (SP) in the spinal cord tissue. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was conducted to detect the relative expression levels of SP and tachykinin receptor 1 (TACR1) mRNA in the hippocampus tissue of rats. Western blot analysis was performed to assess the relative expression levels of vimentin (VIM), nuclear receptor corepressor 1 (NOCR), ciliary neurotrophic factor receptor (CNTFR), and epidermal growth factor receptor (EGFR) proteins in the spinal cord tissue. Results Compared with the normal group, rats in the model group exhibited decreased pain threshold and weight-bearing capacity, increased hind paw temperature and dorsoventral thickness, as well as elevated levels of TNF-α, IL-6, IL-1β, and Glu, increased positive expression rates of Iba-1 and GFAP, heightened positive expression rate and relative mRNA expression levels of SP and TACR1, and augmented relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 0 h before treatment and at 1, 6, 24, and 168 h post-treatment (P < 0.05). Compared with the model group, rats in the fentanyl citrate group showed increased pain threshold and weight-bearing capacity, decreased hind paw temperature and dorsoventral thickness, as well as reduced levels of TNF-α, IL-6, IL-1β, and Glu, decreased positive expression rates of Iba-1 and GFAP, lowered positive expression rate and relative mRNA expression levels of SP and TACR1, and decreased relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 1, 6, 24, and 168 h post-treatment(P < 0.05). Compared with the fentanyl citrate group, rats in the fentanyl citrate+Sar-SP group demonstrated decreased pain threshold and weight-bearing capacity, increased hind paw temperature and dorsoventral thickness, elevated levels of TNF-α, IL-6, IL-1β, and Glu, increased positive expression rates of Iba-1 and GFAP, heightened positive expression rate and relative mRNA expression levels of SP and TACR1, and elevated relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 1, 6, 24, and 168 h post-treatment(P < 0.05). Conclusion The improvement in pain in aged rats with hip fracture by fentanyl citrate may be associated with the reduction of SP expression in the spinal cord that inhibits glial cell activation and exhibits anti-inflammatory effects.

【Objective】 To conduct the laboratory quality assessment between 12 blood stations in Hebei province, analyze the results and explore the accuracy and comparability of testing, so as to improve the level of testing ability and quality management. 【Methods】 With reference to the external quality assessment rules of National Center for Clinical Laboratories and combined with the instructions of quality assessment samples, daily testing process of the laboratories were assessed. The quality indicators include blood cell count (WBC, RBC, Hb, HCT, MCV, MCH, MCHC and PLT), biochemical items (TP) and coagulation parameters (FIB and FⅧ). 【Results】 There are still problems in laboratories in terms of personnel operation, instrument maintenance and the impact of different reagent batches, especially in biochemical items and coagulation parameters. The pass rate of biochemical items was the lowest, only 72.75%, and that of blood cell count was the highest, reaching 98.75%. 【Conclusion】 With the progress of the project, the quality monitoring level of daily blood sampling tests in the quality control laboratory of each blood station has been improved. However, it is still necessary for each laboratory to improve the testing ability and quality management to a higher level in Hebei.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To analyze the flow field characteristics of the upper airway in patients with different adenoid hypertrophy using computational fluid dynamics (CFD). Methods: From November 2020 to November 2021, the cone-beam CT (CBCT) data of 4 patients [2 males and 2 females,age range 5-7 years, mean (6.0±1.2) years] with adenoid hypertrophy who were hospitalized in the Department of Orthodontics and the Department of Otolaryngology at Hebei Eye Hospital were selected. The degree of adenoid hypertrophy in the 4 patients was divided into normal S1 (A/N<0.6), mild hypertrophy S2 (0.6≤A/N<0.7), moderate hypertrophy S3 (0.7≤A/N<0.9) and severe hypertrophy S4 (A/N≥0.9) according to the ratio of adenoid thickness to the width of nasopharyngeal cavity (A/N). The CFD model of the upper airway was established using ANSYS 2019 R1 software, and the internal flow field of the CFD model was numerically simulated. Eight sections were selected as observation and measurement planes for flow field information. Relevant flow field information includes airflow distribution, velocity variation, and pressure variation. Results: In the S1 model, the maximum pressure difference occurred in the 4th and 5th observation planes (ΔP=27.98). The lowest pressures and the maximum flow rates of S2 and S3 were located in the 6th observation plane. The airflow in S1 and S2 models completely passed through the nasal cavity. In the S3 model, the mouth-to-nasal airflow ratio was close to 2∶1. In S4 model, the airflow completely passed through the mouth; in the S1 and S2 models, hard palates were subjected to a downward positive pressure with a pressure difference of 38.34 and 23.31 Pa, respectively. The hard palates in S3 and S4 models were subjected to a downward negative pressure with a pressure difference of -2.95 and -21.81 Pa, respectively. Conclusions: The CFD model can objectively and quantitatively describe the upper airway airflow field information in patients with adenoid hypertrophy. With the increasing degree of adenoid hypertrophy, the nasal ventilation volume gradually decreased, whereas the oral space ventilation volume gradually increased, and the pressure difference between the upper and lower surfaces of the palate gradually decreased until the pressure became negative.

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

Objective To investigate the relationship between the G894T polymorphism of the endothelial nitric oxide synthase (eNOS) gene and the lipid metabolism in patients with irypertensive disorder complicating pregnancy (HDCP). Methods The 528 cases of HDCP patients admitted to the Xingtai Third Hospital from January 2016 to January 2020 were selected as the research objects, and 128 normal pregnant women during the same period were selected as the control group. The fasting peripheral venous blood of all stud)' subjects in the early morning was collected, and blood lipid indexes, cystatin C (CysC) and uric acid levels and other biochemical index levels were measured. According to the blood lipid level, it was divided into normal blood lipid group and dyslipidemia group. The dyslipidemia group included 4 subgroups [ hyper triglyceride (TG) blood group (T G ^ 1. 70 mmol/L), low high-density lipoprotein cholesterol (HDL-C)] Iryper lipidemia group (HDL-C< 1. 04 mmol/L), high total cholesterol (TC) group (TC ^ 5 . 18 mmol/L), mixed hyperlipidemia group (TG ^ 1. 70 mmol/L, TC ^ 5.18 mmol/L)]. In addition, polymerase chain reaction-restriction endonuclease length fragment polymorphism (PCR-RFLP) was used to perform genotyping analysis on the G894T locus of the eNOS gene, which was divided into TT, GT and GG genotypes. The distribution of gene polymorphisms in people with different blood lipid levels was compared, and Logistic regression was used to analyze the influencing factors of dyslipidemia and the relationship between NOS gene G894T polymorphism and dyslipidemia. Results The expected and observed genotypes of GG, GT, TT, eNOS gene G894T locus in the stud)' group and the control group conformed to the Hardy-Weinberg equilibrium law (X' = 0. 651, P = 0. 722 •X' =i. 845, P = 0. 398), and the GG type gene frequency and G allele frequency of the stud)' group were higher than those of the control group, and the TT type gene frequency and T allele frequency of the stud)' group were lower than those of the control group (P < 0. 05); homocysteine (Hey), uric acid, C-reactive protein (CRP).The urine microalbumin to creatinine ratio (UACR) level and body mass index(BMI) were higher than those in the normal blood lipid group, and the rate of taking antihypertensive drugs was lower (P < 0 . 05). Dyslipidemia group eNOS gene (G894T) gene GG gene frequency and G allele were higher than normal blood lipid group, TT gene frequency and T allele were lower than normal blood lipid group (P<0.001). The BMI of patients in the low HDL-C group, hyper TG group and mixed hyperlipidemia group was higher than that of the normal blood lipid group (P< 0. 05); The Hey level of the mixed hyperlipidemia group was higher than that of the normal blood lipid group (P<0. 05). The TT gene frequency and T allele frequency of the low HDL-C group and the mixed hyperlipidemia group were significantly lower than those of the normal blood lipid group, and the GG gene frequency and G allele frequency were higher than the normal blood lipid group (P<0. 05). Logistic regression analysis showed that genotype TT was a protective factor for dyslipidemia in patients with HDCP, and genotype GG, high BMI and high Hey levels were independent risk factors for dyslipidemia. Conclusion There is a significant correlation between the G894T polymorphism of the eNOS gene and dyslipidemia among patients with hypertension in pregnancy. The genotype TT is a protective factor, and the genotype GG/GT is an independent risk factor; at the same time, BMI and Hey will also affect dyslipidemia.