BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

ObjectiveTo establish a high-performance liquid chromatography（HPLC） for the quantitative analysis of multiple components in Gegen Qinlian tablets， and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution（TOPSIS）， in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets. MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers， and taking the detection results as variables， SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis（CA）， principal component analysis（PCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） to identify key components affecting the quality. Then， TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method. ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation， the method was found to be stable and reliable， and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin， puerarin， 3′-methoxy puerarin， daidzein， coptisine hydrochloride， epiberberine， jatrorrhizine hydrochloride， berberine hydrochloride， palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35， 24.88-42.32， 4.20-9.36， 4.33-7.60， 2.52-6.44， 0.93-4.10， 0.58-3.05， 10.68-22.92， 0.82-4.82， 11.73-60.16 mg·g^-1， respectively. Among them， puerarin， berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories， PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%， and OPLS-DA screened out 4 differential markers with variable importance in the projection（VIP） values>1.0， namely baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride， which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index（C_i） values of different manufacturers were different. Among them， the C_i of manufacturer B was ranked higher， indicating potentially superior quality， while the C_i of manufacturer A was ranked lower， suggesting potentially inferior quality. ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets， and the content uniformity of the same manufacturer is good， while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis， it is found that the content differences of Gegen Qinlian tablets may be related to baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride.

OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

[摘 要] 目的：探讨X连锁锌指蛋白（ZFX）通过Nectin-4表达影响食管鳞状细胞癌（ESCC）进展的分子机制及其对PI3K/AKT信号通路的激活作用。方法：收集2022年8月至2023年7月在南充市中心医院手术切除的30对ESCC组织及癌旁组织标本。采用人食管上皮细胞HET-1A及ESCC细胞KYSE-30、KYSE-150、KYSE-410、KYSE-510和TE-1。基于2018年至2019年收集的6例ESCC配对标本转录组测序数据筛选Nectin-4，通过TIMER2.0数据库、RT-qPCR和WB法、免疫组织化学（IHC）检测ESCC组织及细胞中Nectin-4的表达水平。采用shRNA技术在KYSE-410和KYSE-510细胞中敲低Nectin-4，通过CCK-8、克隆形成、划痕愈合及Transwell实验检测敲低Nectin-4对细胞增殖、迁移和侵袭能力的影响，采用WB法检测敲低Nectin-4对细胞PI3K/AKT通路及EMT相关蛋白表达水平的影响。通过生物信息学预测并结合双萤光素酶报告基因实验，鉴定并验证ZFX作为Nectin-4的上游转录调控因子。结果：综合分析显示，ESCC组织及细胞系中Nectin-4表达显著高于癌旁组织及HET-1A细胞（均P < 0.01）。功能研究表明，敲低Nectin-4显著抑制KYSE-410和KYSE-510细胞的增殖活性、克隆形成能力，以及迁移和侵袭能力（均P < 0.01）。机制方面，敲低Nectin-4时细胞中E-cadherin表达上调、N-cadherin下调（均P < 0.01），并抑制PI3K/AKT通路相关蛋白的磷酸化水平（P < 0.01）。结论： ZFX通过上调Nectin-4表达激活PI3K/AKT信号通路促进ESCC进展，为ESCC的治疗提供了潜在的新靶点。

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

Objective:To observe the relationship between preoperative controlling nutritional status(CONUT)score and cognitive impairment,as well as short-term prognosis after intravenous thrombolysis(IVT)in patients with acute ischemic stroke(AIS).Methods:187 patients with AIS who were admitted to Shandong Provincial Third Hospital from January 2023 to May 2024 were selected,they were divided into non cognitive impairment group(n=106)and cognitive impairment group(n=81)based on whether cognitive impairment occurred,they were divided into poor prognosis group(n=58 cases)and good prognosis group(n=129 cases)according to the prognosis.Preoperative CONUT scores of patients with AIS for different cognitive impairments and prognoses were compared,correlation was analyzed by Spearman rank correlation,influencing factors were analyzed by multivariate logistic regression model.Results:Preoperative CONUT score in the cognitive impairment group was higher than that in the non cognitive impairment group(P＜0.05).Preoperative CONUT score in the poor prognosis group was higher than that in the good prognosis group(P＜0.05).Spearman rank correlation test results showed that,preoperative CONUT score was positively correlated with cognitive impairment and short-term prognosis after IVT(P＜0.05).Cognitive impairment were associated with age,concomitant hypertension,baseline national institutes of health stroke scale(NIHSS)score,and 25 hydroxyvitamin D3[25-(OH)2D3](P＜0.05).Age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase were risk factors for cognitive impairment in patients with AIS(P＜0.05).Conclusion:Preoperative CONUT score increase is positively correlated with cognitive impairment and short-term prognosis after IVT.Meanwhile,age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase are risk factors for cognitive impairment in patient with AIS.

Objective To construct a quality evaluation index system for non-medical technical services in public hospitals,aiming to provide a more scientific and feasible basis for evaluating patient service quality.Methods Based on literature research,the SERVQUAL theory was used to preliminarily formulate a comprehensive and full-cycle evaluation index for patient service quality.The final evaluation index system was determined through expert consultation,and the Analytic Hierarchy Process was used to determine the weights of the evaluation indices.Results The questionnaire response rates for the two rounds of expert consultation were both 100％.The authority coefficients of the experts were 0.82 and 0.80,respectively,indicating a high level of expert authority.The Kendall's W coefficient increased from 0.088 to 0.107 between the two rounds,and the difference was statistically significant (P<0.001),indicating good consistency of expert opinions.The consistency results of each judgment matrix were less than 0.1,passing the consistency test.The final evaluation index system consisted of six primary indicators (tangibility,reliability,responsiveness,assurance,empathy,and continuity) and 33 secondary indicators.Conclusion The selection of evaluation indicators revolves around the core service processes of outpatient,inpatient,and other hospital services,focusing on key elements at various critical junctures that influence patient experience.The evaluation indicators aim to guide hospitals to improve not only essential needs but also desired improvements in service quality,thus promoting the continuous enhancement of hospital services.

Objective:To observe the relationship between preoperative controlling nutritional status(CONUT)score and cognitive impairment,as well as short-term prognosis after intravenous thrombolysis(IVT)in patients with acute ischemic stroke(AIS).Methods:187 patients with AIS who were admitted to Shandong Provincial Third Hospital from January 2023 to May 2024 were selected,they were divided into non cognitive impairment group(n=106)and cognitive impairment group(n=81)based on whether cognitive impairment occurred,they were divided into poor prognosis group(n=58 cases)and good prognosis group(n=129 cases)according to the prognosis.Preoperative CONUT scores of patients with AIS for different cognitive impairments and prognoses were compared,correlation was analyzed by Spearman rank correlation,influencing factors were analyzed by multivariate logistic regression model.Results:Preoperative CONUT score in the cognitive impairment group was higher than that in the non cognitive impairment group(P＜0.05).Preoperative CONUT score in the poor prognosis group was higher than that in the good prognosis group(P＜0.05).Spearman rank correlation test results showed that,preoperative CONUT score was positively correlated with cognitive impairment and short-term prognosis after IVT(P＜0.05).Cognitive impairment were associated with age,concomitant hypertension,baseline national institutes of health stroke scale(NIHSS)score,and 25 hydroxyvitamin D3[25-(OH)2D3](P＜0.05).Age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase were risk factors for cognitive impairment in patients with AIS(P＜0.05).Conclusion:Preoperative CONUT score increase is positively correlated with cognitive impairment and short-term prognosis after IVT.Meanwhile,age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase are risk factors for cognitive impairment in patient with AIS.

Tovorafenib has been approved by the U.S.Food and Drug Administration(FDA)for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma(LGGs)harboring the serine threonine kinae v-RAF murine sarcoma viral oncogene homologue B1(BRAF)fusion or rearrangement,or BRAV600E mutation.Tovorafenib is an oral,greater brain-penetrant,selective,type Ⅱ RAF inhibitor which has potent activity against both oncogenic BRAF fusions and BRAFV600E mutations.Most tumors have been showed some degree of shrinkage.The mechanism of action,pharmacodynamics,pharmacokinetics,clinical study and safety were introduced.