BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.

ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription （ZJTP） on human umbilical vein endothelial cells （HUVECs） damaged by high glucose combined with lipopolysaccharide （LPS）. MethodThe survival rate of cells was determined by cell counting kit-8 （CCK-8）， and the level of tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA） to determine the optimal injury concentration and action time of LPS， as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group， a model group， a ZJTP drug-containing serum group， and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 （ET-1）， nitric oxide （NO）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 （GPR43）， β-suppressor protein-2 （β-arrestin-2）， nuclear factor-κB suppressor α （IκBα）， and nuclear factor κB p65 （NF-κB p65）. The nucleation of NF-κB p65 was observed by immunofluorescence staining （IF）. The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid （siRNA）. The cells after intervention were divided into an empty carrier group， a ZJTP drug-containing serum group， a Si-GPR43 group， and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β， IL-6， and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65. ResultThe optimal molding condition was 1 mg·L^-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group， the content of ET-1 in the model group was significantly increased， and the content of NO was significantly decreased （P<0.01）. The levels of inflammatory factors were significantly increased （P<0.01）. The expressions of GPR43 and IκBα were significantly decreased， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased （P<0.01）. NF-κB p65 protein was transferred from the extranuclear to the intranuclear （P<0.01）. Compared with the model group， the content of ET-1 in the ZJTP drug-containing serum group was decreased， and the content of NO was increased （P<0.05）. The levels of inflammatory factors decreased （P<0.05）. The protein expressions of GPR43 and IκBα were increased， while the expressions of β-arrestin-2 and NF-κB p65 were decreased （P<0.05）. The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased （P<0.01）. The mechanism study showed that compared with the Si-GPR43 group， the content of IL-1β， IL-6， and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum （P<0.01）. The protein expressions of GPR43 and IκBα were significantly increased （P<0.01）， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased （P<0.01）. The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased （P<0.01）. ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury， which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Objective:To construct and validate a nomogram for prediction of in-hospital postoperative heart failure(PHF)in elderly patients with hip fracture.Methods:This was a retrospective cohort study.The patients aged ≥65 years undergoing hip fracture surgery in Peking University Third Hospital from July 2015 to December 2023 were enrolled.The patients admitted from July 2015 to December 2021 were divided into a development cohort,and the others admitted from January 2022 to December 2023 in to a validation cohort.The patients'clinical data were collected from the electronic medical record sys-tem.Univariate and multivariate Logistic regression were employed to screen the predictors for PHF in the patients.The R software was used to construct a nomogram.Internal and external validation were per-formed by the Bootstrap method.The discriminatory ability of the model was determined by the area un-der the receiver operating characteristic curve(AUC).The calibration was evaluated by the calibration plot and Hosmer-Lemeshow goodness-of-fit test.Decision curve analysis(DCA)was performed to assess the clinical utility.Results:In the study,944 patients were eventually enrolled in the development co-hort,and 469 were in the validation cohort.A total of 54(5.7％)patients developed PHF in the deve-lopment cohort,and 18(3.8％)patients had PHF in the validation cohort.Compared with those from non-PHF group,the patients from PHF group were older,had higher prevalence of heart disease,hyper-tension and pulmonary disease,had poorer American Society of Anesthesiologists(ASA)classification(Ⅲ-Ⅳ),presented with lower preoperative hemoglobin level,lower left ventricular ejection fraction,higher preoperative serum creatinine,received hip arthroplasty and general anesthesia more frequently.Multivariate Logistic regression analysis showed that age(OR=1.071,95％CI:1.019-1.127,P=0.008),history of heart disease(OR=5.360,95％CI:2.808-10.234,P＜0.001),preoperative he-moglobin level(OR=0.979,95％CI:0.960-0.999,P=0.041),preoperative serum creatinine(OR=1.007,95％CI:1.001-1.013,P=0.015),hip arthroplasty(OR=2.513,95％CI:1.259-5.019,P=0.009),and general anesthesia(OR=2.024,95％CI:1.053-3.890,P=0.034)were the independent predictors for PHF in elderly patients with hip fracture.Four preoperative predictors were incorporated to construct a preoperative nomogram for PHF in the patients.The AUC values of the nomo-gram in internal and external validation were 0.818(95％CI:0.768-0.868)and 0.873(95％CI:0.805-0.929),indicating its good accuracy.The calibration plots and Hosmer-Lemeshow goodness-of-fit test(internal validation:x2=9.958,P=0.354;external validation:x2=5.477,P=0.791)showed its satisfactory calibration.Clinical usefulness of the nomogram was confirmed by decision curve analysis.Conclusion:An easy-to-use nomogram for prediction of in-hospital PHF in elderly patients with hip fracture is well developed.This preoperative risk assessment tool can effectively identify patients at high risk of PHF and may be useful for perioperative management optimization.

Objective:To systematically evaluate the impact of sexual health education on the sexual quality of life, sexual satisfaction, anxiety, depression and the quality of life in breast cancer patients.Methods:A comprehensive search was conducted in Cochrane Library, Embase, PubMed, CNKI, Wanfang Data, VIP, and SinoMed databases for randomized controlled trials (RCTs) exploring the effects of sexual health education on sexual quality of life, sexual satisfaction, anxiety, depression and quality of life in breast cancer patients. The search covered studies up until November 8, 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of the RCTs using the Cochrane Handbook 5.1.0 risk of bias tool. Meta-analysis was performed using RevMan 5.4 and R4.3.2 software.Results:A total of 17 articles with 1 695 patients were included. Sexual health education significantly improved sexual quality of life [ SMD=1.25, 95% CI (0.65, 1.84), P<0.05], sexual satisfaction [ SMD=0.85, 95% CI (0.53, 1.17), P<0.05], depression [ SMD=-1.16, 95% CI (-2.01, -0.30), P<0.05], and the quality of life [ SMD=1.53, 95% CI (0.09, 2.97), P<0.05] in breast cancer patients. However, the improvement in anxiety was not statistically significant [ SMD=-0.88, 95% CI (-2.06, 0.29), P<0.05] . Conclusions:Sexual health education can improve the sexual quality of life, sexual satisfaction, depression, and the quality of life in breast cancer patients. However, its impact on anxiety remains unclear, possibly due to the limited number of studies. Future RCTs should further explore the effect of sexual health education on anxiety in this population.

Objective To investigate the expression of serum CC chemokine ligand 2(CCL2),CX3C chemokine ligand 1(CX3CL1)and CXC chemokine ligand 10(CXCL10)in postmenopausal osteoporosis(PMOP)patients and the value of combination with fracture risk assessment tool(FRAX)in predicting fracture occurrence.Methods A total of 120 patients with PMOP admitted to Hainan West Central Hospital from January 2022 to June 2023 were selected,and they were divided into fracture group(n=52)and non-fracture group(n=68).According to the FRAX score examination,they were divided into a high-risk fracture group(n=73)and a low-risk fracture group(n=47).The levels of serum CCL2,CX3CL1 and CXCL10 in each group were compared.Multivariate Logistic regression was used to analyze the fracture risk factors in PMOP patients.ROC curve was drawn to analyze the value of CCL2,CX3CL1 and CXCL10 combined with FRAX score in predicting fracture of PMOP.Results The levels of serum CCL2(134.98±32.24 pg/ml),CX3CL1(186.25±41.60 pg/ml)and CXCL10(223.47±56.43 pg/ml)in the fracture group were higher than those in the non-fracture group(82.26±17.30 pg/ml,105.23±23.78 pg/ml,151.47±43.14 pg/ml),and the differences were statistically significant(t=11.503,13.452,7.923,all P＜0.001).The levels of serum CCL2(119.70±37.56 pg/ml),CX3CL1(161.43±53.79 pg/ml)and CXCL10(204.06±61.41pg/ml)in the high-risk group for fractures were higher than those in the low-risk group(82.43±17.23 pg/ml,107.55±24.75 pg/ml,149.45±42.50pg/ml),and the differences were statistically significant(t=6.377,6.436,5.327,all P＜0.001).Multivariate Logistic regression analysis showed that elevated levels of serum CCL2,CX3CL1 and CXCL10 were risk factors for fractures in PMOP patients.The ROC curve showed that the combination of CCL2,CX3CL1 and CXCL10 combined with FRAX scores predicted the highest AUC(95％CI)for PMOP fractures[0.951(0.892～0.993)],with sensitivity and specificity of 98.2％and 85.6％,respectively.Conclusion The increased levels of serum CCL2,CX3CL1 and CXCL10 are risk factors for fracture in PMOP patients,and the combination with FRAX score has a good predictive value for fracture.

This paper discusses the theoretical basis of traditional Chinese medicine （TCM） for the treatment of cancer-related fatigue （CRF） based on the principle of treating overstrain with warming in the Huangdi's Internal Classic 《黄帝内经》 and the role of hypothalamic-pituitary-adrenal （HPA） axis dysregulation in CRF， aiming to provide new ideas for the clinical treatment of CRF. In the pulsatile regulation of the HPA axis， cortisol， which is synthesized and released by the adrenal cortex， plays an essential role in the life activities. The abnormal circadian rhythm and reduced serum level of cortisol are major factors leading to CRF. Therefore， increasing the serum level and stimulating the biological activity of cortisol and restoring the normal function of HPA axis are important targets for the treatment of CRF and also the key to the TCM treatment of this disease. According to the TCM principle of treating overstrain with warming， we interpreted the etiology and clinical manifestations of overstrain and further explored the causes of CRF. It is believed that the depletion of Qi and blood， Yin and Yang， and fluid in the kidney， spleen， and liver is the key of the disease， which results in symptoms such as fatigue. Further， we elaborated on the theoretical connotation of warming and summarized the two main treatment principles of tonifying with warm-natured herbs and relieving fever with sweet- and warm-natured herbs. According to the different characteristics of the organs affected by pathogen， we proposed the treatment method of warming kidney to cultivate essence， warming stomach and nourishing spleen to replenish Qi， nourishing liver and tonifying blood to promote Qi movement， and relieving fever with sweet- and warm-natured herbs to alleviate fatigue. The warming method can elevate the serum level and invigorate the biological functions of cortisol in CRF patients， which provides a new theoretical basis for alleviating the symptoms and improving the quality of life of cancer patients in clinical practice.

Gingival recessions (GRs) result in root hypersensitivity, root surface caries, and esthetic problems. Various root coverage surgeries are being developed for periodontal plastic therapy. The tunnel technique (TUN) is one of the most widely applied surgeries due to its features of being minimally invasive, practical, excellent outcomes and long-term stability; however, there are still some limitations of this technique. The history and evolution from the envelope flap to TUN, including its efficiency when compared with coronally advanced flaps with a connective tissue graft (CTG), are reviewed in this paper. The limitations of TUN are discussed in consideration of our clinical experience; for example, there is high technique sensitivity when TUN is applied in GR>5 mm because of the great difficulty in covering the grafts. The advantages of surgical access, including vertical incisions in the vestibule, “W” type and pinhole access, are discussed for different situations. Mattress sutures and sling sutures in a single tooth or multiple teeth are applied in TUN. The different types of grafts, such as CTG, platelet-rich plasma, articular dermal matrix and xenogeneic collagen matrix, are described. Mechanical, chemical and biological conditioning of the root surface are recommended during surgery. Protecting the surgical area and taking antibiotics postoperatively are also very important. Finally, the modifications when TUN is applied with other kinds of techniques are discussed, including lateral closed TUN, laterally positioned flaps, double papilla flaps and frenuloplasty. Minimally invasive, esthetic, long-term stability and simplified techniques are the development trends of TUN in the future.