Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.

Objective To compare the clinical efficacy and pregnancy outcomes of CO2 laser and loop electrosurgical excision procedure(LEEP)surgery in the treatment of cervical high-grade squamous intraepithelial lesion(HSIL)in women of childbearing age.Methods Patients with cervical HSIL of appropriate reproductive age(20-34 years old)who underwent satisfied colposcope,subsequently treated with laser or LEEP between Jan 2019 and Dec 2021 in Obstetrics and Gynecology Hospital,Fudan University were collected.All the patients were interpreted as transformation zone(TZ)type 1/2,and colposcopy biopsy diagnosed as cervical high-grade squamous intraepithelial lesion(HSIL)and received laser or LEEP according to the physician's advice and the patient's wishes.The effectiveness of the two surgeries was evaluated,and postoperative cytology,HPV result,and colposcopic pathology were compared.We monitored the surgical pregnancy rate,pregnancy complications,and pregnancy results after the surgery.Results A total of 566 cases,including 233 laser cases and 333 LEEP cases,were enrolled.There was no significant difference between the two groups in terms of preoperative cytology,HPV distribution,or the length of cervical canal.After 6 months of surgery,91.5%of patients who underwent laser therapy and 86.9%of those who underwent LEEP had normal cytology.The histology cure rate was 91.5%and the HPV conversion rate was 74.6%in both groups.The results of cytology,HPV,and colposcopic pathology had no significant difference between the two groups.The length of postoperative cervical canal was significantly longer in laser group than that in LEEP group[(29.09±3.15)mm vs.(27.05±3.84)mm,P<0.001].There was no statistically significant difference in postoperative pregnancy rate and pregnancy outcome between the two groups.Conclusion Laser ablation and LEEP produce comparable effects pregnancy outcomes in cervical HSIL patients with TZ types 1 and 2,while LEEP has pathologic feedback,so its misdiagnosis of invasive cancer reduce.

italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.

【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8⁺ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56^dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.
Aged ; Aged, 80 and over ; Bundle of His ; Cardiac Pacing, Artificial/methods* ; Electrocardiography/methods* ; Fluoroscopy ; Humans ; Male ; Retrospective Studies ; Stroke Volume ; Transcatheter Aortic Valve Replacement/adverse effects* ; Treatment Outcome ; Ventricular Function, Left

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.
Anastomotic Leak/surgery* ; Humans ; Intestinal Obstruction/surgery* ; Laparoscopy ; Postoperative Complications/surgery* ; Prospective Studies ; Rectal Diseases/surgery* ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Syndrome ; Treatment Outcome

Objective: To study the effects of exosome secreted by ovarian cancer (OC) cell on the differentiation and metastasis of normal fibroblasts (NFs). Methods: NFs were collected from patients who underwent hysteromyoma resection in the Affiliated Hospital of Qingdao University from May to December 2019. Exosome was extracted from the culture supernatant of SKOV3 cells by using ultra-high-speed centrifugation. The NFs were co-cultured with condition medium (CM), exosome of SKOV3 (SKOV3-exo) and control medium. The expression levels of fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA) were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. The metastatic ability of NFs was detected by Transwell array. Results: Under the transmission electron microscope, the extracellular vesicles extracted from the culture supernatant of SKOV3 were 30-100 nm in diameter with cup holder-like bilayer membrane structure, and the protein expression levels of TSG101 and HSP27 in exosomes (1.00±0.05 and 1.12±0.13) were higher than those of ovarian cancer SKOV3 cells (0.22±0.21 and 0.36±0.14, respectively, P<0.05). PKH67 fluorescently labeled exosomes could be taken up by NFs. The expression levels of α-SMA and FAP mRNA in CM group(2.91±0.15 and 3.21±0.33)and SKOV3-exo group (3.50±0.21 and 4.63±0.24, respectively) were higher than that in blank group (1.00±0.06 and 1.00±0.13, P<0.05). The protein expression levels of α-SMA and FAP in CM group and SKOV3-exo group (0.89±0.11 and 1.25±0.09, 0.81±0.09 and 1.20±0.12) were higher than those in the blank group (0.12±0.31 and 0.11±0.19, respectively, P<0.05). The migrated numbers of cells in the CM group and SKOV3-exo group [(215.01±14.80) and (389.72±19.43), respectively] were higher than that in the blank group [(113.73±4.70), P<0.05]. Conclusion: The exosome secreted by SKOV3 cells can be taken up by NFs, which makes it to differentiate into cancer associated fibroblasts (CAFs) and significantly enhances its metastatic ability, indicating that OC cells may promote the transformation of normal ovarian mesenchymal fibroblasts to CAFs through exosome pathways, and then promote the development of ovarian cancer.
Carcinoma, Ovarian Epithelial ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Exosomes ; Female ; Fibroblasts ; Humans ; Ovarian Neoplasms/metabolism*

In order to better control the quality of Flos Puerariae(FP),qualitative and quantitative analyses were initially performed by using chemical fingerprint and chemometrics methods in this study.First,the fingerprint of FP was developed by HPLC and the chemical markers were screened out by similarity analysis(SA),hierarchical clustering analysis(HCA),principal components analysis(PCA),and orthogonal partial least squares discriminant analysis(OPLS-DA).Next,the chemical constituents in FP were profiled and identified by HPLC coupled to Fourier transform ion cyclotron resonance mass spectrometry(HPLC-FT-ICR MS).Then,the characteristic constituents in FP were quantitatively analyzed by HPLC.As a result,31 common peaks were assigned in the fingerprint and 6 of them were considered as qualitative markers.A total of 35 chemical constituents were detected by HPLC-FT-ICR MS and 16 of them were unambiguously identified by comparing retention time,UV absorption wavelength,accurate mass,and MS/MS data with those of reference standards.Subsequently,the contents of glycitin,genistin,tectoridin,glycitein,genistein,and tectorigenin in 13 batches of FP were detected,ranging from 0.4438 to 11.06 mg/g,0.955 to 1.726 mg/g,9.81 to 57.22 mg/g,3.349 to 41.60 mg/g,0.3576 to 0.989 mg/g,and 2.126 to 9.99 mg/g,respectively.In conclusion,fingerprint analysis in combination with chemometrics methods could discover chemical markers for improving the quality control standard of FP.It is expected that the strategy applied in this study will be valuable for further quality control of other traditional Chinese medicines.