[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。

OBJECTIVE: To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery (MD+S) and surgery alone in the treatment of testicular torsion, and to provide some new evidence for the timely diagnosis and treatment of the disease. METHODS: We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022. We statistically analyzed the age distribution, and duration and degrees of testicular torsion, followed by comparison between the two groups. RESULTS: In the 134 cases, the median age of onset was 15 (13－19) years old, the median onset-to-visit time was 15 (8－25) hours, and the median degree of torsion was 360° (180°－1080°). Of the total number of patients, 21 underwent testicular excision and the other 113 were treated with the testis preserved, with no statistically significant difference in age distribution between the two groups (P>0.05), and a higher rate of testis resection in those with longer duration and greater angle of torsion (P<0.05). Totally, 33 of the patients were assigned to the MD+S group and 101 to the surgery alone group. According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °, 28 of the patients underwent ultrasound-guided MD+S (with 1 case of testis resection, 3.6%), and 68 received surgery alone (with 7 cases of testis resection, 10.3%). The rate of testis resection was higher in the surgery alone than that in the MD+S group, but with no statistically significant difference between the two groups (P>0.05), which was considered to be related to the small sample size in this study. CONCLUSION The popularization of testicular torsion knowledge can shorten the onset-to-visit time, and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.
Humans ; Male ; Spermatic Cord Torsion/therapy* ; Retrospective Studies ; Adolescent ; Young Adult ; Ultrasonography ; Testis/surgery* ; Adult

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 comprehensively explore the serological characteristics of anti-PP1P^k and potential therapeutic strategies for recurrent miscarriage in p-blood type pregnant women. 【Methods】 Neutralization with pigeon egg white and human plasma, disruption of IgM antibodies by 2-mercaptoethanol reagent, and complement adding were conducted. Anti-PP1P^k titers under different processing conditions, media and temperatures were determined, and neutralizing effect of human plasma on anti-PP1P^k and its sensitization complement ability were analyzed. 【Results】 The titers of anti-PP1P^k in saline and column agglutination were 4 and 8, respectively. Low temperature increased titers, while β-mercaptoethanol treatment significantly reduced them. Pigeon egg white partially neutralized anti-PP1P^k antibodies. Human plasma was also capable of reducing anti-PP1P^k titers with neutralization capability surpassing that of pigeon egg white, and there were individual differences in neutralization capability. 【Conclusion】 The anti-PP1P^k was a blend of antibodies encompassing both IgM and IgG types, exhibiting cold reactivity, and having the potential for complement activation. Human plasma emerges as an effective modulator for diminishing the efficacy of anti-PP1P^k. Plasma transfusion holds promise as a therapeutic avenue for addressing recurrent miscarriages in pregnant individuals with the p phenotype.

OBJECTIVE: To construct a risk prediction model for elderly severe patients with pneumonia infection, and analyze the prevention effect of 1M3S nursing plan under early warning mode. METHODS: Firstly, 180 elderly severe patients admitted to the department of intensive care unit (ICU) of the Second Affiliated Hospital of Xingtai Medical College from September 2020 to September 2021 were enrolled. Their clinical data were collected and retrospectively analyzed, and they were divided into infected group and non-infected group according to whether they developed severe pneumonia. The risk factors affecting severe pneumonia in elderly severe patients were screened by univariate and multifactorial analysis methods, and the risk prediction model was constructed. The predictive efficiency of the model was analyzed by receiver operator characteristic curve (ROC curve). Then the risk prediction model was applied to prospectively include 60 high-risk elderly patients with severe pneumonia admitted from December 2021 to August 2022. The patients were randomly divided into study group and control group by envelope method, with 30 cases in each group. Both groups were given routine nursing. On this basis, the study group adopted 1M3S nursing scheme [standardized nursing management (1M), improving nursing skills (S1), optimizing nursing service (S2), ensuring nursing safety (S3)] in the early warning mode for intervention. Acute physiology and chronic health evaluation II (APACHE II) and Murray lung injury score were compared between the two groups before intervention and 7 days after intervention. RESULTS: Among 180 elderly severe patients, 34 cases were infected with pneumonia (18.89%). The proportion of patients with Glasgow coma scale (GCS) ≤ 8, duration of mechanical ventilation > 7 days, use of antibiotics, poor oral hygiene, hospital stay > 15 days and albumin ≤ 30 g/L in the infected group were significantly higher than those in the non-infected group. Multivariate Logistic regression analysis showed that duration of mechanical ventilation > 7 days, use of antibiotics, GCS score≤ 8, hospital stay > 15 days, albumin ≤ 30 g/L and poor oral hygiene were all independent risk factors for severe pneumonia in elderly severe patients. The odds ratio (OR) values were 3.180, 3.394, 1.108, 1.881, 1.517 and 2.512 (all P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of the prediction model to predict severe pneumonia in elderly severe patients was 0.838, 95% confidence interval was 0.748-0.927, sensitivity and specificity were 81.25% and 72.57%, respectively, and the Youden index was 0.538. (2) There was no significantly difference in general data between the study group and the control group, which was comparable. After intervention, the APACHE II score and Murray lung injury score of the two groups were significantly decreased, and the APACHE II score and Murray lung injury score of the study group were significantly lower than those of the control group (APACHE II score: 3.15±1.02 vs. 3.81±0.25, Murray lung injury score: 5.01±1.12 vs. 6.55±0.21, both P < 0.01). CONCLUSIONS There are many risk factors affecting the development of severe pneumonia in elderly severe patients. The risk prediction model based on duration of mechanical ventilation > 7 days, hospital stay > 15 days, GCS score≤ 8, albumin ≤ 30 g/L, poor oral hygiene and history of combined antibacterial use has high predictive efficacy. The intervention of 1M3S nursing scheme in the early warning mode can effectively reduce the risk of severe pneumonia in elderly severe patients, and significantly improve the pathophysiological status.
Humans ; Pneumonia/diagnosis* ; Aged ; Risk Factors ; Retrospective Studies ; Intensive Care Units ; Female ; Male ; ROC Curve ; Risk Assessment/methods*

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 To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia- inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜ 0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）. CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.

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