OBJECTIVES: According to the World Health Organization (WHO), infertility rates have been steadily rising worldwide. Identifying risk factors for contrast agent reflux into the myometrium during hysterosalpingo-contrast sonography (HyCoSy) is of clinical significance in reducing this complication and improving infertility treatment. However, there is currently no standardized pre-evaluation method for predicting intra-myometrial contrast reflux, with clinical assessment often relying on physician experience and patient symptoms. This study aims to identify imaging risk factors for contrast agent reflux into the myometrium using four-dimensional (4D) HyCoSy and to construct a nomogram-based predictive model to assist in clinical decision-making. METHODS: A retrospective analysis was conducted on 1 274 infertile women who underwent 4D HyCoSy at the Women and Children's Hospital of Hunan and the the Third Xiangya Hospital of Central South University from January 1, 2020, to December 15, 2022. Patients were divided into a reflux group (n=234) and a non-reflux group (n=1 040) based on the presence of intra-myometrial contrast reflux. Univariate and multivariable Logistic regression analyses were used to identify significant predictors, which were then used to construct a nomogram model. Internal validation was performed using 500 bootstrap resamples. RESULTS: The age of the reflux group was significantly higher than that of the non-reflux group [(31.82±5.27) years vs (30.66±4.83) years, P=0.001 1]. Primary infertility was more common in the non-reflux group (50.96%), while secondary infertility dominated in the reflux group (76.50%), with 72.65% having a history of gynecological surgery (P<0.001). Abnormal menstrual volume and discomfort during the procedure were more common in the reflux group, while the non-reflux group tolerated higher contrast agent doses (P<0.001). Imaging differences included endometrial thickness, tubal wall smoothness, and peritoneal contrast dispersion, with the non-reflux group showing thicker endometrium and smoother, more patent tubes. The nomogram model yielded an area under the curve (AUC) of 0.854, indicating good predictive performance. The AUC of the decision curve analysis (DCA) for internal validation of the model was 0.737. When the threshold probability for contrast agent reflux into the myometrium ranged from 0.05 to 0.95, the maximum net benefit reached 0.18. The net benefit of applying the nomogram predictive model exceeded that of either full intervention or no intervention, indicating that the model demonstrates good clinical predictive performance. CONCLUSIONS The nomogram model, based on infertility type, endometrial thickness, contrast agent dose, and discomfort symptoms, effectively predicts intra-myometrial contrast agent reflux after 4D HyCoSy. It provides a valuable tool for clinicians to implement early preventive measures and reduce the risk of contrast leakage and associated complications.
Humans ; Female ; Nomograms ; Contrast Media/adverse effects* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Hysterosalpingography/methods* ; Infertility, Female/diagnostic imaging* ; Myometrium/diagnostic imaging* ; Risk Factors

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

OBJECTIVE: To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance. METHODS: Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC₅₀ value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot. RESULTS: The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001). CONCLUSION AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.
Cell Line ; Cytarabine/pharmacology* ; Drug Resistance ; Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Messenger/genetics* ; Sirtuin 1

Objective: To investigate the factors affecting postpartum stress urinary incontinence (PSUI) among lying-in women at ages of 35 years and older, so as to provide insights into PSUI prevention. Methods: Lying-in women at ages of 35 years and older receiving postpartum examinations were sampled using a convenient sampling method from Hangzhou Obstetrics and Gynecology Hospital during the period from January 2021 to April 2022. Participants' demographic data, type of delivery, birth weight, diastasis recti abdominis, pelvic floor muscle strength injury, pelvic floor muscle training were collected, and the development of PSUI was evaluated using the International Consultation on Incontinence modular questionnaire. The factors affecting the development of PSUI were identified among lying-in women at ages of 35 years and older using a multivariable logistic regression model. Results: A total of 230 questionnaires were allocated, and 226 valid questionnaires were recovered, with an effective recovery rate of 98.26%. The lying-in women had a mean age of (37.30±2.11) years, and 75.66% had a pre-pregnancy body mass index (BMI) of 18.5 to 24.0 kg/m2. There were 29 women with postpartum BMI of 24.0 kg/m2 and greater (12.83%), 201 women with gestational weeks of 37 weeks and greater at delivery (88.94%), 105 women with vaginal delivery (46.46%), 20 women with neonatal birth weights of 4 000 g and higher (8.85%), 149 women with diastasis recti abdominis (65.93%), 154 women with pelvic floor muscle strength injury (68.14%). The prevalence of PSUI was 25.22% among the study subjects. Multivariable logistic regression analysis showed that vaginal delivery (OR=4.061, 95%CI: 2.124-7.763), postpartum BMI of 24 kg/m2 and higher (OR=1.903, 95%CI: 1.275-3.288), neonatal birth weight of 4 000 g and higher (OR=2.108, 95%CI: 1.420-4.135), diastasis recti abdominis (OR=1.487, 95%CI: 1.110-2.169) and pelvic floor muscle strength injury (OR=2.924, 95%CI: 1.726-4.803) were risk factors for PSUI among lying-in women at ages of 35 years and older, and pelvic floor muscle training was a protective factor for PSUI among lying-in women at ages of 35 years and older (OR=0.410, 95%CI: 0.216-0.780). Conclusions The development of PSUI correlates with the type of delivery, postpartum BMI, neonatal birth weight, diastasis recti abdominis and pelvic floor muscle strength injury among lying-in women. Reasonable weight control and active pelvic floor muscle training may facilitate the prevention of PSUI.

Objective:To investigate the incidence, risk factors and early prognosis of acute kidney injury (AKI) after heart valve surgery in adults, and to provide evidence for the early prevention and treatment of AKI after heart valve surgery.Methods:Clinical data of patients undergoing heart valve surgery from January 2016 to March 2017 were collected retrospectively. Early postoperative AKI was diagnosed and staged according to Kidney Disease Improving Global Outcomes (KDIGO) clinical guidelines for AKI. Patients were divided into AKI group and non-AKI group according to whether AKI occurred within 48 hours after surgery, and the differences in clinical indexes between the two groups were compared and analyzed. Influencing factors for early postoperative AKI were screened by stepwise multivariate logistic regression.Results:A total of 600 patients were enrolled, including 197 patients in the AKI group and 403 patients in the non-AKI group. The incidence of AKI was 32.83%. In the non-AKI and AKI groups, proportion of renal replacement therapy (RRT) during hospitalization, mechanical ventilation time, intensive care unit (ICU) time and proportion of hospital mortality were different (all P<0.001). In the AKI group, 160 patients (81.22%) were in stage I, 33 patients (16.75%) were in stage Ⅱ, and 4 patients (2.03%) were in stage Ⅲ. The proportion of patients receiving RRT, mechanical ventilation time, ICU time, hospital mortality were also different in patients with AKI of different stages (all P<0.05). Logistic regression analysis results showed that males, body mass index≥24.0 kg/m 2, previous history of cardiac surgery, baseline serum creatinine >115 mmol/L, albumin<35 g/L, aortic occlusion time (AOT)>90 min, blood glucose in ICU after operation>11.1 mmol/L, the difference between the highest blood glucose within 48 hours after the operation and the blood glucose at 0 h after the operation≥2 mmol/L, blood lactic acid in ICU after operation>4 mmol/L and maximum vasoactive drug score within 48 hours after surgery>9 were independent influencing factors for early AKI (all P<0.05). Conclusions:The incidence of AKI within 48 hours after heart valve surgery is over 30%. The independent influencing factors include male, overweight/obesity, previous cardiac surgery, preoperative renal insufficiency, hypoproteinemia, long duration of AOT, post-operative stress hyperglycemia, fluctuating blood glucose levels wildly, hyperlactacidemia, and using more vasoactive drugs. AKI after cardiac surgery affects the early prognosis of patients, the later of the stage leads to the worse prognosis.

OBJECTIVE: To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model. METHODS: Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay. RESULTS: Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01). CONCLUSIONS decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; Liver ; drug effects ; pathology ; Liver Neoplasms ; drug therapy ; immunology ; metabolism ; pathology ; Mice ; Necrosis ; Neoplasm Proteins ; metabolism ; Random Allocation ; Up-Regulation

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

To determine the contents of salvianolic acid B and borneol in compound Danshen tablet (composed of Salviae Miltiorrhizae Radix et Rhizome, Notoginseng Radix et Rhizome and Borneolum Syntheticum) by near-infrared spectroscopy (NIR) and to establish a dependency model for rapid quantitative analysis. NIR data of 74 batches of compound Danshen tablet from different companies were collected; the contents of salvianolic acid B and borneol were determined by using high performanceliquid chromatography (HPLC) and gas chromatography (GC) respectively to establish the dependency model for salvianolic acid B and borneol. The results showed that the best waveband for salvianolic acid B was 10 846.2-10 013, 9 195.3-8 362.2, 6 719.1-4 242.8 cm⁻¹; root-mean-squares error of cross-validation (RMSECV), coefficient of determination ² and regression point displacement (RPD) of salvianolic acid B were 1.72 mg·g⁻¹, 91.05% and 7.93 mg·g⁻¹, respectively. While the best wavebands, RMSECV, ² and RPD of borneol were 10 846.2-5 060.5 cm⁻¹, 1.2 mg·g⁻¹, 96.11% and 6.71 mg·g⁻¹，respectively. The relative error of the established model as validation results for validation set samples was 2.67% and 4.64%， respectively.With the good predictability, the models can be applied to the real time monitoring and quality control of compound Danshen tablet.