The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

In this single-arm prospective cohort study, the aim was to evaluate the antihypertensive efficacy and safety of the angiotensinⅡreceptor-neprilysin inhibitor sacubitril/valsartan in patients with refractory hypertension (RH) undergoing peritoneal dialysis. A total of 67 peritoneal dialysis patients with regular treatment for ≥ 3 months and confirmed RH were enrolled. Sacubitril/valsartan was added to the background antihypertensive therapy and titrated according to a standardized protocol for 6 months. Data on RH control, demographic and clinical characteristics, and adverse reactions were collected before and after intervention. The mean values of valid 24 h ambulatory blood pressure recordings, nocturnal systolic blood pressure (SBP) dipping percentage, blood pressure variability parameters, and the blood pressure control rate were compared before and after treatment. Laboratory and clinical data were also compared. After a median follow-up of 8.0 (4.0, 12.5) months, 50 patients completed the study. After treatment, all blood pressure parameters significantly decreased compared with baseline. The mean values of valid 24 h SBP decreased by 9.52 mmHg ( t=4.79, P<0.001) and the mean values of valid 24 h diastolic blood pressure (DBP) decreased by 7.55 mmHg ( t=5.90, P<0.001). Day-time SBP decreased by 10.82 mmHg ( t=5.22, P<0.001) and day-time DBP by 8.41 mmHg ( t=6.28, P<0.001). Night-time SBP decreased by 6.93 mmHg ( t=2.81, P=0.007) and night-time DBP by 4.95 mmHg ( t=3.12, P=0.003). The standard deviation (SD) of 24 h-SBP ( t=2.43, P=0.018), 24 h DBP-SD ( t=3.82, P<0.001), day-time DBP-SD ( t=2.80, P=0.007), and the coefficient of variation of 24 h-DBP ( t=2.04, P=0.046) were significantly reduced. The blood pressure control rate increased from 14.90% to 44.80% ( χ2=12.89, P<0.001). During follow-up, no patient experienced acute deterioration of renal function. One case of hyperkalemia returned to normal after appropriate treatment, and no serious adverse events occurred. These findings suggest that sacubitril/valsartan effectively lowers blood pressure and improves the blood pressure control rate in peritoneal dialysis patients with RH, with favorable safety and tolerability.

Objective To explore the perioperative therapeutic effects and follow-up manage-ment in 16 patients with left ventricular assist device(LVAD)implantation.Methods A retrospec-tive analysis was conducted in data of 16 patients who underwent LVAD implantation in the depart-ment of cardiovascular surgery.Data of 6-minute walk test(6MWT),European Quality of Life-5 Di-mension-5 Levels(EQ-5D-5L),New York Heart Association(NYHA)classification,echocardio-graphy,chest radiography,cardiothoracic ratio,and occurrence of complications(infection,bleed-ing,thrombosis,right heart failure,neurological issues)were collected via the electronic medical re-cord system before surgery and at 30,60,and 90 days postoperatively.Results All patients sur-vived with the pump at 90 days postoperatively.One patient with preoperative renal insufficiency un-derwent dialysis and received a heart transplant after 8 months.One patient developed a sterile granu-loma at the percutaneous lead site on the abdominal wall,which improved after treatment,no complica-tions occurred in other patients.At 90 days postoperatively,there was no statistically significant differ-ence in the right ventricular area change fraction and tricuspid annular plane systolic excursion com-pared with preoperative values(P＞0.05).The left ventricular ejection fraction,left ventricular end-diastolic diameter,and cardiothoracic ratio showed significant improvement compared with preoperative levels(P＜0.05).At 30 days postoperatively,30％of patients recovered to NYHA class Ⅰ and 70％to class Ⅱ;at 60 days,80％of patients to class Ⅰ and 20％to class Ⅱ;at 90 days,90％to classⅠ and 10％to class Ⅱ.The 6MWT and EQ-5D-5L scores of patients significantly increased within 90 days postoperatively(P＜0.01).Conclusion Through rigorous preoperative assessment by a multidisciplinary LVAD team,refinement of surgical techniques,and comprehensive management during hospitalization,self-management before discharge,daily follow-up after discharge,and fol-low-up management upon returning to the hospital for patients with LVAD implantation,the cardiac function and quality of life of patients are significantly improved at 90 days postoperatively.

In this single-arm prospective cohort study, the aim was to evaluate the antihypertensive efficacy and safety of the angiotensinⅡreceptor-neprilysin inhibitor sacubitril/valsartan in patients with refractory hypertension (RH) undergoing peritoneal dialysis. A total of 67 peritoneal dialysis patients with regular treatment for ≥ 3 months and confirmed RH were enrolled. Sacubitril/valsartan was added to the background antihypertensive therapy and titrated according to a standardized protocol for 6 months. Data on RH control, demographic and clinical characteristics, and adverse reactions were collected before and after intervention. The mean values of valid 24 h ambulatory blood pressure recordings, nocturnal systolic blood pressure (SBP) dipping percentage, blood pressure variability parameters, and the blood pressure control rate were compared before and after treatment. Laboratory and clinical data were also compared. After a median follow-up of 8.0 (4.0, 12.5) months, 50 patients completed the study. After treatment, all blood pressure parameters significantly decreased compared with baseline. The mean values of valid 24 h SBP decreased by 9.52 mmHg ( t=4.79, P<0.001) and the mean values of valid 24 h diastolic blood pressure (DBP) decreased by 7.55 mmHg ( t=5.90, P<0.001). Day-time SBP decreased by 10.82 mmHg ( t=5.22, P<0.001) and day-time DBP by 8.41 mmHg ( t=6.28, P<0.001). Night-time SBP decreased by 6.93 mmHg ( t=2.81, P=0.007) and night-time DBP by 4.95 mmHg ( t=3.12, P=0.003). The standard deviation (SD) of 24 h-SBP ( t=2.43, P=0.018), 24 h DBP-SD ( t=3.82, P<0.001), day-time DBP-SD ( t=2.80, P=0.007), and the coefficient of variation of 24 h-DBP ( t=2.04, P=0.046) were significantly reduced. The blood pressure control rate increased from 14.90% to 44.80% ( χ2=12.89, P<0.001). During follow-up, no patient experienced acute deterioration of renal function. One case of hyperkalemia returned to normal after appropriate treatment, and no serious adverse events occurred. These findings suggest that sacubitril/valsartan effectively lowers blood pressure and improves the blood pressure control rate in peritoneal dialysis patients with RH, with favorable safety and tolerability.

ObjectiveTo improve the response capabilities to disasters and prevent major epidemics， it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises， to enhance the overall quality of the teams. MethodsFirst， a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification （IEC） standards of the national emergency medical rescue team. Then， based on the outcome based education （OBE） concept， we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally， an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023， as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators， the five core competencies in the evaluation system， including rescue skills， medical and health knowledge， disaster coping ability， team cooperation ability， and mental resilience training， were positively correlated with the cumulative number of trainings （r=0.71， r=0.76， r=0.81， r=0.84， r=0.96，all P<0.05）， indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.Thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

Objective:To investigate the effect of high-dose vitamin D combined with insulin on serum homocysteine (HCY), glucose and lipid metabolism and pregnancy outcome in patients with gestational diabetes mellitus.Methods:From June 2020 to May 2023, 120 patients with gestational diabetes mellitus in Yan'an People's Hospital were selected as the research object, and they were randomly divided into observation group and control group with 60 cases in each group. The control group was treated with insulin aspart, while the observation group was treated with insulin aspart and large dose of vitamin D. The levels of serum HCY, glucose metabolism, serum 25-hydroxyvitamin D3 and blood lipid metabolism were compared between the two groups before and after treatment. The pregnancy outcomes of the two groups were compared and analyzed through follow-up.Independent sample t-test is used for comparison between two groups of econometric data that conform to normal distribution, while paired t-test is used for comparison within groups. The comparison between the groups was performed by χ2 test. Results:After treatment, fasting blood glucose ((4.67±0.52) mmol/L vs (5.46±0.68) mmol/L), 2-hour postprandial blood glucose ((6.67±0.56) mmol/L vs (8.42±0.78) mmol/L) and homeostasis model insulin resistance index (2.45±0.45 vs 3.87±0.34) in the observation group were significantly lower than those in the control group, and homeostasis model assessment of islets in pre diabetes patients β cell function index (HOMA-β) in the observation group was significantly higher than that in the control group (87.15±10.45 vs 75.92±10.06). The differences were statistically significant (t values were 7.15, 14.12, 19.50, and 6.00; all P<0.001). After treatment, the serum HCY level ((8.72±1.27) μmol/L vs (10.18±1.65) μmol/L), in the observation group was lower than that in the control group and the serum 25-OH-D3 level ((15.05±2.41) μg/L vs (11.25±2.37) μg/L) in the observation group was higher than that in the control group. The differences were statistically significant ( t=5.43, 8.71, P<0.001). After treatment, the serum triglyceride, total cholesterol and low density lipoprotein cholesterol (LDL-C) in the observation group were compared with those in the control group. LDL-C levels were lower than those in the control group ((2.15±0.15) mmol/L vs (3.23±0.18) mmol/L, (5.23±0.14) mmol/L vs (6.34±0.17) mmol/L, (1.53±0.21) mmol/L and (2.21±0.22) mmol/L), serum high density lipoprotein cholesterol (HDL-C), HDL-C levels were significantly higher than those in the control group ((1.18±0.11) mmol/L vs (0.98±0.12) mmol/L), and the differences were statistically significant (t-values were 35.70, 39.04, 17.32, and 9.52, respectively, all P<0.001). The incidence of adverse pregnancy outcome in the observation group was lower than that in the control group (10% (6/60) vs 40% (24/60)), and the difference was statistically significant ( χ2=14.28, P<0.001). Conclusion:High-dose vitamin D combined with insulin therapy can not only effectively improve glucose and lipid metabolism, but also reduce the HCY level and improve the adverse pregnancy outcome in patients with gestational diabetes mellitus.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignant tumor with unique geographical and ethnic distribution characteristics. NPC is mostly found in south China and Southeast Asia, and its treatment mainly depends on radiotherapy and chemotherapy. However, NPC is usually found in the late stage, and local recurrence and distant metastasis are common, leading to poor prognosis. The receptor tyrosine kinase AXL is up-regulated in various tumors and it is involved in tumor proliferation, migration, invasion, and other processes, which are associated with poor prognosis of tumors. This study aims to detect the expression of AXL in NPC cell lines and tissues, and to investigate its biological function of AXL and the underlying molecular mechanisms in regulation of NPC. METHODS: The expression levels of AXL in normal nasopharyngeal epithelial tissues and NPC tissues were analyzed by GSE68799, GSE12452, and GSE53819 data sets based on Gene Expression Omnibus (GEO) database. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between AXL and prognosis of head and neck squamous cell carcinoma (HNSC). The indicators of prognosis included overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). Western blotting assay was used to detect the AXL protein expression levels in normal nasopharyngeal epithelial cell line and NPC cell lines. Immunohistochemical method was used to detect AXL expression levels in normal nasopharyngeal epithelial tissues and NPC tissues. Cell lines with stable AXL knockdown were established by infecting 5-8F and Fadu cells with lentivirus interference vector, and cell lines with stable AXL overexpression were established by infecting C666-1 and HK-1 cells with lentivirus expression vector. Real-time PCR and Western blotting were used to detect the efficiency of knockdown and overexpression in stable cell lines. The effects of AXL knockdown or overexpression on proliferation, migration, and invasion of NPC cells were detected by CCK-8, plate colony formation, and Transwell assays, and the effect of AXL knockdown on tumor growth in nude mice was detected by subcutaneous tumor formation assay. The sequence of AXL upstream 2.0 kb promoter region was obtained by UCSC online database. The PROMO online database was used to predict AXL transcription factors with 0% fault tolerance, and the JASPAR online database was used to predict the binding sites of ETS1 to AXL. Real-time PCR and Western blotting were used to detect the effect of ETS1 on AXL protein and mRNA expression. The AXL upstream 2.0 kb promoter region was divided into 8 fragments, each of which was 250 bp in length. Primers were designed for 8 fragments. The binding of ETS1 to AXL promoter region was detected by chromatin immuno-precipitation (ChIP) assay to determine the direct regulatory relationship between ETS1 and AXL. Rescue assay was used to determine whether ETS1 affected the proliferation, migration, and invasion of NPC cells through AXL. RESULTS: Bioinformatics analysis showed that AXL was highly expressed in NPC tissues (P<0.05), and AXL expression was positively correlated with OS, DFI, DSS, and PFI in HNSC patients. Western blotting and immunohistochemical results showed that AXL was highly expressed in NPC cell lines and tissues compared with the normal nasopharyngeal epithelial cell line and tissues. Real-time PCR and Western blotting results showed that knockdown and overexpression efficiency in the stable cell lines met the requirements of subsequent experiments. The results of CCK-8, plate colony formation, Transwell assays and subcutaneous tumor formation in nude mice showed that down-regulation of AXL significantly inhibited the proliferation, migration, invasion of NPC cells and tumor growth (all P<0.05), and the up-regulation of AXL significantly promoted the proliferation, migration, and invasion of NPC cells (all P<0.05).As predicted by PROMO and JASPAR online databases, ETS1 was a transcription factor of AXL and had multiple binding sites in the AXL promoter region. Real-time PCR and Western blotting results showed that knockdown or overexpression of ETS1 down-regulated or up-regulated AXL protein and mRNA expression levels. ChIP assay result showed that ETS1 bound to AXL promoter region and directly regulate AXL expression. Rescue assay showed that AXL rescued the effects of ETS1 on proliferation, migration and invasion of NPC cells (P<0.05). CONCLUSIONS AXL is highly expressed in NPC cell lines and tissues, which can promote the malignant progression of NPC, and its expression is regulated by transcription factor ETS1.
Animals ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/metabolism* ; RNA, Messenger/genetics* ; Sincalide/metabolism* ; Transcription Factors/genetics*

ObjectiveTo develop a two-dimensional high-performance liquid chromatography （2D-HPLC） for simultaneous determination of the contents of four kinds of Uncaria alkaloids： rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine. MethodsThe 2D-HPLC apparatus was comprised of a first chromatographic column in version Aston SC2 （3.5 mm×25 mm， 5 μm）， an intermediate column in version Aston SH C₁₈ （3.5 mm×10 mm， 5 μm）， and an analytical column in version Aston SCB （4.6 mm×125 mm， 5 μm）. The mobile phase of the first and second liquid chromatography system were CAA-1 and mixed mobile phase （V _{BPI-1 basic mobile phase} ∶ V _{MPI-1 mobile phase} ∶ V _{OPI-1 organic mobile phase} = 45∶14∶41）. The chromatographic parameters included a flow rate of 1.0 mL/min， a column temperature of 40℃， a wavelength of 254 nm， an injection volume of 500 μL and a detection time of 9.5 min. ResultsThe linear ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 9.77~10 000.00 ng/mL （r=0.999 6）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL（r=0.999 6）， respectively. The relative standard deviation （RSD） of precision， stability and repeatability were all less than 5.00%. The accuracy was 95.20%~104.01%， and the recovery rate was 93.63%~101.38%. ConclusionThe 2D-HPLC developed for simultaneous determination of four kinds of alkaloids in Uncaria is simple and accurate， which can be used as a new method for quality control of Uncaria.

ObjectiveTo determine the contents of four kinds of indole alkaloids （rhynchophylline， isorhynchophylline， corynoxeine， isocorynoxeine） in Uncaria by high-performance liquid chromatography-mass spectrometry-automatic internal standard （HPLC-MS-AIS）. MethodsChromatographic separation was performed using C₁₈ column （3.0 mm×50 mm， 3.3 μm）， and the mobile phase， comprising 0.1% formic acid aqueous solution-acetonitrile （82∶18， V/V）， was eluted at a flow rate of 0.5 mL/min and column temperature of 30℃. Mass spectrometric detection was performed using an electrospray ionization source and positive multiple-reaction monitoring mode at a voltage capillary of 4 000 V. The mass-to-charge ratio （m/z） transition was 385.25/160.10 for rhynchophylline， 385.30/160.10 for isorhynchophylline， 383.25/160.15 for corynoxeine and 383.25/160.15 for isocorynoxeine， respectively. The injection volume was kept constant at 2 μL. ResultsThe linear concentration ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 2.30~600.00 ng/mL （r=0.999 3）， 2.30~600.00 ng/mL （r=0.999 2）， 2.47~650.00 ng/mL （r=0.999 4） and 2.47~650.00 ng/mL （r=0.999 2）， respectively. The relative standard deviation （RSD） of precision and stability were all lower than 5.00%， the accuracy ranged from 92.40% to 104.10%， and the average recovery was 95.90%~104.60%. ConclusionHPLC-MS-AIS method is simple and accurate for the determination of four kinds of alkaloids in Uncaria， and can be used as a new method for quality control of Uncaria.