ObjectiveTo investigate the mechanism by which Shenqi Yiliu prescription reverses cisplatin resistance in ovarian cancer cells by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway-mediated glycolysis. MethodsThe human ovarian cancer A2780 cell line was intervened with progressively increasing doses of cisplatin （1 g·L^-1） to establish the cisplatin-resistant cell line A2780cisR， and the cell sensitivity to cisplatin was examined by the cell counting kit-8 （CCK-8） assay. High， medium， and low （39.9， 19.95， 9.98 g·kg^-1） doses of Shenqi Yiliu prescription-containing sera were used to treat A2780cisR cells for 48 h. Glucose consumption and lactate production were measured by the cuvette assay. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the activities of glucose transporter （GLUT）， phosphofructokinase （PFK）， and pyruvate kinase （PK）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect apoptosis. Western blot was employed to quantify the protein levels of phosphorylated （p）-PI3K， p-Akt， p-mTOR， hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， B-cell lymphoblastoma-2 （Bcl-2）， Bcl-2-associated X-protein （Bax）， and B-lymphoblastoma-2 gene-related promoter （Bad）. Real-time PCR was conducted to determine the mRNA levels of HK2， PKM2， Bax， Bcl-2， and Bad. ResultsThe median inhibitory concentration （IC₅₀） of cisplatin on A2780cisR cells was nearly 3 times that on A2780P cells. Compared with A2780P cells， A2780cisR cells showed increased glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax （P<0.05）， and decreased apoptosis rate and Bcl-2 expression （P<0.05）. Compared with A2780cisR cells， medium- and high-dose Shenqi Yiliu prescription reduced the glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax， and Bad （P<0.05）， while increasing the apoptosis rate and Bcl-2 expression （P<0.05）. ConclusionShenqi Yiliu prescription can inhibit glycolysis mediated by the PI3K/Akt/mTOR pathway to promote apoptosis， thereby reversing cisplatin resistance in ovarian cancer cells.

[摘 要] 目的：探讨胃肝样腺癌（HAS）的临床病理特征与免疫微环境异质性，筛选预后标志物，阐释其高侵袭性与疗效差的机制，为精准诊疗策略提供理论依据。方法:​​ 回顾性收集2013年1月至2025年5月期间海军军医大学第一附属医院与第二附属医院收治的65例HAS患者的临床信息及病理资料。采用免疫组织化学技术检测HAS​​肝样分化标志物、神经内分泌标志物​​等分子表达情况，通过Kaplan-Meier生存分析法明确与预后相关的靶点。利用多色免疫荧光技术鉴定肿瘤区域内免疫细胞亚群分布情况，以阐明其免疫微环境特征。结果：65例患者中，男性54例（83.1%），女性11例（16.9%），中位年龄68岁。肿瘤好发于贲门（40%），其次为胃窦（32.3%）和胃体（27.7%）。中位随访时间23.18个月，15例患者死亡，46例生存，4例失访。HAS的胃镜及手术标本大体观呈灰白色实性质硬肿物，镜下可见中低分化胃腺癌与肝细胞癌（HCC）样分化区交错分布。表达神经内分泌相关分子的HAS患者呈现出更多的淋巴结转移数量及更短的总生存期。免疫微环境解析显示，HAS总体缺乏免疫细胞浸润，呈现“冷肿瘤”特征；免疫细胞主要聚集于胃癌腺体周围区域，而在HCC样分化区域罕见淋巴细胞浸润。结论：HAS侵袭性强，根治性手术是主要治疗手段；神经内分泌转化提示不良预后，是个体化治疗的关键标志；免疫细胞浸润缺乏，可能是其免疫治疗响应不佳的原因。

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

ObjectiveTo focused on patients with unexplained repeated implantation failure （URIF） and compare the clinical efficacy of different administration routes of granulocyte colony-stimulating factor （G-CSF） in patients undergoing frozen-thawed embryo transfer cycles. MethodsA retrospective case-control study was conducted. A total of 187 patients with URIF who received medical treatment were enrolled in this study. According to whether G-CSF was used on the day of endometrial transformation and its administration route in frozen-thawed embryo transfer cycles， the patients were divided into three groups： control group （without G-CSF， n=71）， subcutaneous injection group （subcutaneous G-CSF， n=72）， and intrauterine infusion group （intrauterine G-CSF infusion， n=44）. The pregnancy outcomes among the three groups were compared， and Logistic regression analysis was performed. ResultsThere were significant differences in biochemical pregnancy rates among the three groups （P<0.05）， indicating statistical significance in the overall comparison. In terms of numerical trend， the biochemical pregnancy rate was in the order： subcutaneous injection group > intrauterine infusion group > control group. Further pairwise comparison showed that only the difference between the subcutaneous injection group and the control group was statistically significant （P<0.017）， while no significant differences were found between the other groups （P>0.017）. The overall comparison of early miscarriage rates among the three groups also showed a significant difference （P<0.05）， indicating a statistically significant difference in the distribution among the groups. The numerical trend was： intrauterine perfusion group > subcutaneous injection group > control group. Pairwise comparison results showed that only the difference between the intrauterine perfusion group and the control group was statistically significant （P<0.017）， while there was no statistically significant difference between any other two groups （P>0.017）.Multivariate Logistic regression analysis showed that endometrial thickness on the day of transformation， number of transferred embryos， and subcutaneous G-CSF injection were independent factors associated with an increased biochemical pregnancy rate， where as age was an independent factor for a decreased biochemical pregnancy rate. For clinical pregnancy outcome， endometrial thickness on the day of transformation， number of transferred embryos， and subcutaneous G-CSF injection were also independent factors for an increased clinical pregnancy rate， while BMI was an independent factor for a decreased clinical pregnancy rate. ConclusionSubcutaneous injection of G-CSF only improved the biochemical pregnancy rate in URIF patients. Multivariate Logistic regression analysis showed that subcutaneous G-CSF injection was a favorable factor for clinical pregnancy rate in URIF patients； however， no significant improvement in clinical pregnancy rate was observed among the three groups. Both the comparison of pregnancy outcomes and the results of multivariate logistic regression analysis indicates that intrauterine perfusion of G-CSF has no significant therapeutic effect in the treatment of patients with URIF.

Objective To identify the impact of glucose variability(GV)on the development of gestational hyper-tension(GH)in patients with gestational diabetes mellitus(GDM),and to find the differences between various GV metrics as well as to evaluate their predictive value in management strategy development.Methods A total of 127 pregnant women diagnosed with GDM were included in this study.After the diagnosis of GDM,continuous glu-cose monitoring(CGM)and blood pressure measurements were performed,and the occurrence of gestational hyper-tensive disorders was recorded.Indices of glucose variability were calculated using an automated software EasyGV version 9.0.Results The results revealed an association between gestational hypertension and glucose variability in GDM patients.Among the study participants,2 cases(1.6％)were diagnosed with preeclampsia and 9 cases(7.1％)were diagnosed with gestational hypertension.TBR％(time below range)showed a significantly negative correlation with diastolic blood pressure at 29-32 weeks of gestation and with both diastolic and systolic blood pres-sure during delivery.TIR％(time in range)showed a negative correlation with the rate of change in systolic blood pressure between two prenatal visits.CONGA(continuous overlapping net glycemic action)emerged as an inde-pendent predictor of gestational hypertension(OR:3.648;95％CI:1.046,12.721;P=0.042).When CONGA exceeded 4.856,the risk of gestational hypertension in GDM patients increased.Conclusions Blood glucose varia-tion is an independent factor affecting the occurrence of pregnancy-induced hypertension in GDM women.This study suggests new targets for the use and management of CGM in pregnant women with GDM.For GDM patients at high risk of hypertensive disease during pregnancy,blood glucose should be kept at a reasonable and stable level.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

Objective To investigate the impact of permissive low-calorie feeding on nutritional status and prognosis in patients with severe pneumonia in the intensive care unit(ICU).Methods A total of 100 patients with severe pneumonia in ICU were selected and divided into low-calorie feeding group and adequate feeding group using a random number table method,with 50 patients in each group.The low-calorie feeding group received permissive low-calorie feeding,and the adequate feeding group received adequate feeding,both conducting for a duration of one week.Clinical indicators,nutri-tional indicators,inflammatory indicators,respiratory function indicators,and intestinal mucosal barrier function indicators were compared between the two groups before treatment and one week after treatment.The incidence of hospital-acquired pneumonia(HAP)and complications(including septic shock,pul-monary edema,bronchiectasis,etc.)were also compared between the two groups.Results The fever clearance time,mechanical ventilation time,and ICU stay duration were shorter in the low-calo-rie feeding group compared to the adequate feeding group(P＜0.05).There was no statistically sig-nificant difference in 28-day mortality between the two groups(P＞0.05).After treatment,there were no statistically significant differences in serum total protein(TP),prealbumin(PA),hemoglobin(HGB),and albumin(ALB)levels between the low-calorie feeding group and the adequate feeding group(P＞0.05).The levels of procalcitonin(PCT)and high-sensitivity C-reactive protein(hs-CRP)were lower in the low-calorie feeding group compared to the adequate feeding group(P＜0.05).The oxygenation index,ventilation volume,mean arterial pressure,and central arterial pressure were lower in the low-calorie feeding group compared to the adequate feeding group(P＜0.05).The levels of D-lactic acid and diamine oxidase(DAO)were also lower in the low-calorie feeding group compared to the adequate feeding group(P＜0.05).The incidence of HAP and complica-tions was 4.00％and 10.00％in the low-calorie feeding group and 14.00％and 18.00％in the adequate feeding group,respectively,with no statistically significant differences(P＞0.05).Con-clusion Permissive low-calorie feeding has a positive effect on the early recovery of ICU patients with severe pneumonia,which can improve respiratory function and intestinal mucosal barrier func-tion and reduce inflammatory levels.

Objective To establish educational milestones for nursing students at different educational stages and compare their distinctions and interrelationships.Methods Methodologies including literature review,role analysis,brainstorming,and the Delphi expert consultation method were used to determine the competency level classification framework and the target competency levels for different categories of students,thereby to formulate the educational milestones.Results A competency classification framework comprising 7 levels was developed.This culminated in an educational milestone system for nursing students,which includes 7 first-level competency indicators,17 second-level competency indicators,61 third-level indicators,and their correspondig target proficiency levels.Conclusion The milestone system can delineate the training objectives for various core competency dimensions among different student categories and illustrate their distinctions and connections.This system is conducive to enhancing the specificity,differentiation,and systematicity of nursing education.

Objective:To explore the implementation method of the "daily-monthly-quarterly" quality control model based on total quality management (TQM) theory in nursing quality management, and evaluate its application effectiveness.Methods:A quasi-experimental research method was used. The quarterly quality control model employed at Shanxi Medical University Second Hospital from 2018 to 2019 was set as the control group, and the"day-month-quarter" quality control model based on TQM implemented from 2020 to 2022 was set as the observation group. The nurse practice environment assessment scores from 2018 to 2022 were analyzed; the nursing quality-sensitive indicators between the two groups were compared, including the incidence rate of overall adverse event, falls among hospitalized patients, pressure ulcers of stage 2 and above, unplanned extubations, and catheter-related infections (central venous catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections).Results:The nurse practice environment assessment scores from 2018 to 2022 were (69.11 ± 19.66), (75.20 ± 18.70), (77.60 ± 17.65), (82.45 ± 16.44), and (88.00 ± 15.06). The differences compared to the previous year were statistically significant ( t=3.63-9.24, all P<0.05).After the intervention, the incidence rates of overall adverse events, falls among hospitalized patients, unplanned extubation, central venous catheter-related bloodstream infections, and ventilator-associated pneumonia in the control group were 0.385% (499/129 678), 0.072% (94/129 678), 0.051% (66/129 678), 0.037% (23/62 390), and 0.746% (43/5 761). Compared to 0.258% (551/213 851), 0.048% (103/213 851), 0.033% (71/213 851), 0.019% (19/98 642), and 0.444% (88/19 826) in the observation group. The differences were statistically significant ( χ2values were 3.89-42.83, all P<0.05). There were no statistically significant differences in the incidence rates of pressure ulcers of stage 2 and above and catheter-associated urinary tract infections (both P>0.05). Conclusions:The "daily-monthly-quarterly" quality control model based on TQM is beneficial in improving nursing quality and ensuring patient safety.