NbCl5-catalyzed sulfa-Michael addition for constructing quaternary centers in enones.

A novel NbCl5-catalyzed sulfa-conjugate addition has been developed to construct quaternary centers in various enones. This new method enables a range of functionalized thiols to access different ß-sulfido carbonyl compounds bearing a quaternary center. 27 novel ß-sulfido ketones have been obtained with moderate to excellent yields. The preparative scale reactions also proceed well, showing no decrease in yield. We further studied the mechanism by DFT calculations. This methodology is significant in sulfur chemistry, especially in sulfa-conjugate addition, giving a new pathway to add thiols to tri-substituted enones.

Carbon dot decorated Co3O4 nanozymes responsive to the NIR-II window for mild photothermal-enhanced nanocatalytic therapy.

Although NIR-II laser-mediated photothermal therapy (PTT) is considered as an emerging strategy for tumor therapy, its therapeutic effects are still seriously hampered by low photothermal conversion efficacy, limited tissue penetration depth, and inevitable damage to adjoining healthy tissues. Herein, we report a mild second-near-infrared (NIR-II) photothermal-augmented nanocatalytic therapy (NCT) nanoplatform based on CD@Co3O4 heterojunctions by depositing NIR-II-responsive carbon dots (CDs) onto the surface of Co3O4 nanozymes. The as-prepared Co3O4 nanozymes possess multi-enzyme-mimicking catalytic activity including peroxidase, catalase, and glutathione-peroxidase to realize the cascade amplification of ROS levels owing to the presence of multivalent Co2+ and Co3+. CDs with a high NIR-II photothermal conversion efficiency (PCE) (51.1%) enable the realization of mild PTT (∼43 °C), which could not only avoid damage to adjoining healthy tissues but also enhance the multi-enzyme-mimic catalytic activity of Co3O4 nanozymes. More importantly, the NIR-II photothermal properties of CDs and the multi-enzyme-mimicking catalytic activity of Co3O4 nanozymes are greatly augmented by the fabrication of heterojunctions due to the induced localized surface plasmonic resonance (LSPR) and accelerated carrier transfer. On the basis of these advantages, satisfactory mild PTT-amplified NCT is accomplished. Our work presents a promising approach for mild NIR-II photothermal-amplified NCT based on semiconductor heterojunctions.

Robotic-assisted laparoscopic and thoracoscopic approach: a challenging multidisciplinary minimally invasive surgery of intravascular leiomyomatosis with intracardiac extension.

OBJECTIVE: To show a case of severe intravascular leiomyomatosis with intracardiac extension treated by a multidisciplinary minimally invasive surgery. DESIGN: Stepwise demonstration of the technique with a video. SETTING: General Hospital. PATIENT(S): A 40-year-old woman with palpitation and dyspnea. INTERVENTION(S): The patient was diagnosed with intravascular leiomyomatosis by computed tomography scan. She underwent a successful single-stage minimally invasive surgery with complete excision. MAIN OUTCOME MEASURE(S): The feasibility and safety of using this technique for intravascular leiomyomatosis with intracardiac extension. RESULT(S): A combined thoracoabdominal surgery was successfully performed. During the procedure, cardiopulmonary bypass was maintained for 72 minutes. The patient soon recovered and was discharged. CONCLUSION(S): Minimally invasive surgery is a possible choice for intravascular leiomyomatosis with intracardiac extension.

4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway.

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

Case Report and Review of Literature: Camrelizumab Combined with Fuzuloparib and Apatinib for Platinum-Resistant Recurrent Ovarian Cancer.

Background: The mortality rate of ovarian cancer (OC) ranks first among female genital tract malignant tumors, which seriously threatens women's life and health. Because of its insidious onset and poor prognosis, it has become a thorny problem in the clinic, especially for patients with platinum-resistant recurrent ovarian cancer (PROC). In recent years, the medical treatment of OC has made gratifying results, bringing hope to the patients. Case Description: A 54-year-old OC patient who has failed previous neoadjuvant chemotherapy, cytoreductive surgery, and postoperative chemotherapy was diagnosed with PROC. Then she received combination treatment of fuzuloparib (100mg PO BID), apatinib (250mg PO QD), and camrelizumab (200mg IV Q3W) for every 3-week cycle in a Phase II study for PROC patients. In the phase II study, her condition stabilized, responded well to treatment with a sharp decrease by 91.14% of target lesions and disappearances of non-target lesions, and continued to receive regular treatment with progression-free survival exceeding 15 months and no serious adverse events. Conclusion: The present case proves PROC patients might have a sustained response to triplet combination with camrelizumab, combined with fuzuloparib and apatinib.

Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE-/- mice.

Atherosclerosis (AS) is a serious threat to the health and life of humans worldwide. The mitigating effect of polyphenol compounds from peanut skin extract (PSE) on AS has attracted great research attention. However, the mechanism underlying this mitigating effect remains poorly understood. This study aims to investigate the preventive effect of PSE on high-fat diet-induced AS in mice and explore the underlying mechanisms. PSE treatment significantly reduced atherosclerotic plaques, particularly at high doses. Dietary PSE intervention obviously alleviated the lipid metabolism disorder in ApoE-/- mice by reducing the serum TC and LDL-C contents and increasing the HDL-C content. In addition, PSE intervention significantly decreased the level of pro-inflammatory cytokines TNF-α and IL-6 and increased that of anti-inflammatory IL-10, thus exhibiting a significant anti-inflammatory effect. More interestingly, analysis of the 16S rRNA gene sequence revealed that PSE could significantly alter the community composition of the gut microbiota. Specifically, PSE enhanced the abundance of Roseburia, Rothia, Parabacteroides and Akkermansia, and reduced that of Bilophila and Alistipes. Some of these intestinal bacteria exhibited good anti-inflammatory effects, which are related to the production of short chain fatty acids. Thus, the anti-atherosclerotic effect of PSE may be partly attributed to changes in the composition and function of gut microbiota, which may be closely associated with its anti-inflammatory effect. Moreover, untargeted metabolomics analysis indicated that PSE could regulate the levels of differential metabolites in the liver, serum and fecal samples.

Robotic-Assisted Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse: A Single Center Experience in China.

OBJECTIVE: The aim is to investigate the efficiency and outcome of robotic-assisted sacrocolpopexy (RASC) in a cohort of patients with pelvic organ prolapse (POP) in our Gynecology Department. METHODS: We performed a retrospective study of female patients who underwent RASC in Chinese PLA General Hospital from January 2013 to December 2020. Their clinical features included age, degree of prolapse, menopause time, body mass index, pregnancy, delivery, operation time, and bleeding volume. All patients were followed up for more than 6 months. POP-Q was recorded to evaluate the position of prolapsed organs. PFDI-20, PFIQ-7, and PGI-I were used to evaluate the life quality after surgery. RESULTS: Twenty-four patients with POP received RASC in our center. The intraoperative bleeding was 86.9 ± 98.3 ml (20-300 ml). The operation time was 143.5 ± 47.3 min (60-240 minutes). The hospitalization time was 10.4 ± 2.1 days (8-16 days). And the follow-up time was 40.8 ± 22.0 months (6-72 months). In the POP-Q follow-up, postoperative Aa, Ba, Ap, Bp, and C were significantly improved than those before surgery (P < 0.05). The objective and subjective cure rate was 100%. PGI-I score was very good in 9 (9/24), very good in 10 (10/24), and good in 3 (3/24). Postoperative PFDI-20 and PFIQ-7 were 2.78 ± 3.82 and 1.57 ± 3.86, which decreased dramatically after surgery (P < 0.05). Mesh exposure occurred in 4 cases (16.7%) at 2-12 months. The exposed diameters were less than 1 cm in 3 cases (2 A/T3/S1) and 1-2 cm in 1 case (3 B/T3/S1). These mesh exposures healed after conservative observation or mesh excision. CONCLUSION: RASC for POP has the advantage of less bleeding and hospitalization time. It is a minimally invasive option for pelvic organ prolapse.

Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network.

PURPOSE: The etiology and pathophysiology of endometriosis remain unclear. Current research indicates long noncoding RNA (lncRNA) may play an important role in the pathogenesis and development of endometriosis. However, the molecular mechanism of lncRNA in endometriosis is far from clear. PATIENTS AND METHODS: The lncRNA and mRNA expression of 8 patients with ovarian endometriosis were determined by high-throughput RNA sequencing (8 ectopic endometria samples vs 8 eutopic endometria samples), and miRNA expression profiles were obtained from our previous study. Then a lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by combining the regulatory interaction and negative co-expression interaction between the differentially expressed lncRNAs/mRNAs and miRNAs by different rules. RESULTS: The constructed lncRNA-related ceRNA network was composed of two separate networks, network 1 including 14,137 dysregulated lncRNA-mRNA interactions, referring to 242 lncRNAs, 55 miRNAs and 1600 mRNAs, network 2 including 4459 dysregulated lncRNA-mRNA interactions, referring to 111 lncRNAs, 39 miRNAs and 1151 mRNAs. The top six hub lncRNAs (LINC01140, MSC-AS1, HAGLR, CKMT2-AS1, JAKMIP2-AS1, AL365361.1) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 1, and the top six hub lncRNAs (PAX8-AS1, MIR17HC, PART1, HOXA-AS3, PLAC4, LINC00511) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 2 were selected. Functional enrichment analysis of these lncRNA-related mRNAs indicated that the lncRNAs in network 1 mainly take part in positive regulation of phagocytosis, myeloid leukocyte activation, and tissue remodeling, while the lncRNAs in network 2 mainly take part in negative regulation of cell proliferation, blood vessel development and regulation of epithelial cell differentiation, which is consistent with the results obtained from the different rules to construct the networks. CONCLUSION: lncRNA-related ceRNA network analysis recognized key lncRNAs related to the development of endometriosis.

A Successful Pregnancy after Laparoscopic Surgery: Severe Recurrent Pelvic Arteriovenous Malformation Managed by Laparoscopic Internal Iliac Artery Ligation.

STUDY OBJECTIVE: To show a case of severe pelvic arteriovenous malformation (AVM) treated by laparoscopic internal iliac artery ligation after 2 uterine artery embolization (UAE) procedures, where successful pregnancy was achieved after surgery. DESIGN: Stepwise demonstration of the technique with a video. SETTING: Chinese PLA General Hospital. INTERVENTIONS: A 36-year-old woman with heavy menstrual bleeding was diagnosed with pelvic AVM by computed tomography scan. Before surgical intervention, she underwent 2 UAE procedures that temporarily reduced menstrual blood loss. Finally, we performed a laparoscopic internal iliac artery ligation on her. After the surgery, she conceived naturally. During the cesarean section, no AVMs were found. CONCLUSION: Laparoscopic internal iliac artery ligation can be a choice for patients who still have severe symptoms of AVM after UAE.

Robotic CSP Resection and Hysterotomy Repair.

STUDY OBJECTIVE: To demonstrate a technique for the robot-assisted laparoscopic surgical management of cesarean section scar ectopic pregnancy (CSP) and hysterotomy repair. DESIGN: Step-by-step presentation of the procedure using video. SETTING: CSP is a rare form of ectopic pregnancy. The incidence of CSP has been increasing with rising cesarean deliveries and is estimated to range from 1 of 1800 to 1 of 2500 of all pregnancies. Various management of CSP have been used such as systemic or local methotrexate, surgical resection, and uterine artery chemoembolization. Exogenic or deep CSP occurs when the gestational sac is deeply embedded in the scar and the surrounding myometrium and grows toward the bladder. Surgical resection of this type of CSP seemed reasonable, which could shorten hospitalization and follow-up time and reduce the failure rate of treatment. For its magnification of the 3-dimensional laparoscope, flexibility endo-wrist, and stabilization of instruments within the surgical field, robot-assisted laparoscopic resection can be performed to manage this type of complex procedure. INTERVENTIONS: In this video, we describe our technique for robot-assisted laparoscopic management of a CSP and a hysterotomy repair. We present the case of a 34-year-old gravida 2 para 1 woman with the finding of a 7-week pregnancy embedded in the cesarean section scar. The patient had undergone 1 previous uncomplicated cesarean section at term. On presentation, her ß-human chorionic gonadotropin level was 9212 IU/L. In this case, the gestational sac was deeply embedded in the scar and the surrounding myometrium and was growing toward the bladder. A decision was made to proceed with surgical treatment in the form of a robot-assisted laparoscopic resection of the ectopic pregnancy and the hysterotomy repair. The surgery was uneventful, and the patient was discharged home within 48 hours of her procedure. No residual scar defect was visible on follow-up ultrasonography 1 month after surgery. Forty days after surgery, the patient had resumed normal menstruation and was followed up for 3 years with regular menstruation and no abnormal uterine bleeding. CONCLUSION: Robot-assisted laparoscopic excision of CSP and hysterotomy repair is an effective procedure for the management of this increasingly more common condition. The use of a cervix dilator and robot-assisted laparoscopic suturing can prevent hemorrhage and peripheral tissue damage and allow for the safe removal of the ectopic pregnancy with multilayer repair of the uterine defect.

Healing effects of a protein scaffold loaded with adipose-derived mesenchymal stem cells on radiation-induced vaginal injury in rats.

OBJECTIVES: Cervical cancer, the most common female cancer after breast cancer, is typically treated using radiotherapy. However, pelvic radiotherapy can cause irreversible damage to the vagina, seriously affecting patients' quality of life. In this study, protein scaffolds loaded with rat adipose-derived mesenchymal stem cells (ADSCs) were implanted into irradiated tissue to assess their healing potential. METHODS: We established a rat model of radiation-induced vaginal injury. Complexes (consisting of protein scaffolds loaded with ADSCs) were implanted into injury sites. Histological analysis were used to assess regeneration of the vaginal epithelium. RNA sequencing was used to study the therapeutic mechanism of the complexes. RESULTS: The complexes promoted vaginal epithelial cell regeneration, vaginal tissue repair and improved vaginal stenosis and contracture. Compared with rats transplanted with ADSCs, rats transplanted with complexes achieved better therapeutic effects. CONCLUSIONS: Protein scaffold-ADSC complexes had a beneficial therapeutic effect on radiation-induced vaginal injury in rats and may serve as the basis of a novel therapeutic approach for radiation dermatitis.

Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis.

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study.

PURPOSE: The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development. METHODS: Real-Time qPCR was used to detect Casein kinase 2 interacting protein-1 (CKIP-1) and Nuclear factor E2-related factor 2 (Nrf2) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP-1 and Nrf2. Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2. RESULTS: CKIP-1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1ß) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP-1 and aggravated by knocking down CKIP-1. Of note, we found that overexpressed CKIP-1 activated Nrf2/ARE signaling pathway and increased its downstream targets including HO-1, NQO-1, γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP-1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2/ARE signaling pathway. CONCLUSION: We concluded that overexpressed CKIP-1 alleviated DR progression by activating Nrf2/ARE signaling pathway.

Cervical cancer evaluated with integrated 18F-FDG PET/MR.

The current study aimed to evaluate the correlation between maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin) of cervical cancer using an integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance (PET/MR) imaging system, and to determine the association with pathological prognostic factors. A total of 46 patients were pathologically diagnosed with cervical cancer and underwent PET/MR prior to surgery, including total hysterectomy, bilateral pelvic lymph node dissection or paraaortic lymph node dissection. The imaging biomarkers included the SUVmax and ADCmin. The pathological prognostic factors were as follows: Tumor size, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. Pearson's correlation analysis was used to evaluate the correlation between imaging biomarkers and the tumor size and the Mann-Whitney U test analysis was used to evaluate the association between imaging biomarkers and pathological factors. The mean SUVmax was 11.1±8.7 (range, 3.16-51.6) and the mean ADCmin was 0.76±0.15×10-3 mm2/s (range, 0.47-1.04×10-3 mm2/s). The SUVmax had a significant negative correlation with the ADCmin (r=-0.700; P<0.001). The SUVmax was significantly increased in patients with poorly differentiated tumors (P=0.001), patients with FIGO stage IIB (P=0.005) and the patients with lymph node metastasis (P=0.040). The ADCmin was significantly decreased in patients with poorly differentiated tumors (P<0.001) and patients with FIGO stage IIB (P=0.017). Statistical analysis revealed no significant correlation between the tumor size and the SUVmax (r=0.286;P=0.054), or between the tumor size and the ADCmin (r=-0.231; P=0.122). Area under the curve (AUC) analysis revealed that SUVmax had a higher diagnostic value for lymph node metastasis (AUC=0.681) and FIGO staging (AUC=0.837) compared with ADCmin, whereas ADCmin had a higher diagnostic value for the grade of pathological differentiation (AUC=0.816) compared with SUVmax (AUC=0.788). The results of the current study demonstrated that there was a significant negative correlation between SUVmax and ADCmin, which were associated with prognostic factors.

Establishment of the PDTX model of gynecological tumors.

OBJECTIVE: Fresh tumor tissues from patients with gynecological tumors were obtained by surgery or biopsy, and transplanted into NOD-Prkdcem26ll2rgem26Nju (NCG) mice to establish a patient-derived tumor xenograft (PDTX). MATERIALS AND METHODS: A total of 15 patients with gynecologic tumors were enrolled into the present study. Among these patients, 12 patients had epithelial fallopian tube/ovarian/peritoneal cancer, one patient had metastatic ovarian cancer, and two patients had cervical cancer. Furthermore, among these patients, three patients were treated with puncture or microscopy biopsy, six patients underwent laparoscopic surgery, and six patients underwent robotic surgery. The tumor formation latency, tumor formation rate, tumor volume, tumor invasion and metastasis of the transplanted tumor were observed, the consistency of the PDTX model tumor tissue and patient's primary tumor tissue was compared by pathological H&E staining, and pharmacodynamics testing was performed. RESULTS: Seven of 15 PDTX models were successfully established, with a success rate of 46.7%. The tumor formation time ranged within 21-130 days, with a median tumor formation time of 73 days. The PDTX model maintained the differentiation, morphological and structural characteristics of tumor cells, and the pharmacodynamic test was completed in five patients. CONCLUSION: The PDTX model is highly consistent with the pathology of the patient's tumor, and can be used as a substitute for clinical patients to guide the accurate treatment and scientific research of gynecological tumors.

Comparison of integrated PET/MRI with PET/CT in evaluation of endometrial cancer: a retrospective analysis of 81 cases.

BACKGROUND: The objective of this study was to compare the diagnostic value of integrated PET/MRI with PET/CT for assessment of regional lymph node metastasis and deep myometrial invasion detection of endometrial cancer. METHODS: Eighty-one patients with biopsy-proven endometrial cancer underwent preoperative PET/CT (n = 37) and integrated PET/MRI (n = 44) for initial staging. The diagnostic performance of PET/CT and integrated PET/MRI for assessing the extent of the primary tumor and metastasis to the regional lymph nodes was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar's test was employed for statistical analysis. RESULTS: Integrated PET/MRI and PET/CT both detected 100% of the primary tumors. Integrated PET/MRI proved significantly more sensitivity and specificity than PET/CT in regional lymph node metastasis detection (P = 0.015 and P < 0.001, respectively). The overall accuracy of myometrial invasion detection for PET/CT and Integrated PET/MRI was 45.9% and 81.8%, respectively. Integrated PET/MRI proved significantly more accurate than PET/CT (P < 0.001). CONCLUSION: Integrated PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for the assessment of the lymph node metastasis and myometrial invasion in patients with endometrial cancer.

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China.

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.

Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling.

Oxidative stress serves a vital function in the pathogenesis of age­related macular degeneration (AMD); genipin (GP) possesses antioxidative properties. The present study aimed to investigate the effects of GP on retinal pigment epithelial (RPE) cells induced by H2O2 and the underlying mechanism. ARPE­19 cells were subjected to H2O2 treatment to induce oxidative damage. Cell viability was determined via an MTT assay. Reactive oxygen species (ROS) levels and cell apoptosis were detected by flow cytometry. Nuclear factor­erythroid 2­related factor­2 (Nrf2) signaling­associated and the expression of apoptosis­associated factors were measured using reverse transcription­quantitative polymerase chain reaction assay and western blotting. The results revealed that 200 µM H2O2 and 30 µM GP were determined to be the optimal concentrations for subsequent experimentation. GP reversed the inhibitory effects of H2O2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increased the expression of Nrf2, heme oxygenase­1 (HO­1) and NAD(P)H: Quinine oxidoreductase 1 (NQO1); Nrf2 silencing inhibited HO­1 and NQO1 expression. In addition, Nrf2 silencing enhanced the effects of H2O2 by promoting ROS production and cell apoptosis. Compared with H2O2, Nrf2 silencing further decreased the expression levels of B­cell lymphoma­2 (Bcl­2), but increased that of Bcl­2­associated X protein and cleaved­caspase­3. The results of the present study revealed that Nrf2 silencing attenuated the protective effects of GP on H2O2­induced injury in ARPE­19 cells by promoting apoptosis and oxidation. Collectively, GP attenuated oxidative damage induced by H2O2 in ARPE­19 cells. Furthermore, the molecular mechanism may be associated with the Nrf2 signaling pathway. The findings of the present study nay provide insight into a potential therapeutic agent for the treatment of AMD.

Tear Luminex Analysis in Dry Eye Patients.

BACKGROUND The purpose of this study was to analyze tear inflammatory cytokines of different subclasses of dry eye disease (DED) patients using Luminex technology. MATERIAL AND METHODS Forty-five DED patients including 20 Sjogren syndrome aqueous tear deficiency (SS-ATD) patients, 20 non-Sjogren syndrome aqueous tear deficiency (NSS-ATD) patients, 15 meibomian gland dysfunction (MGD) patients, and 15 normal participants were enrolled in this study. Concentrations of 11 inflammatory cytokines in tear samples of study participants were measured by Luminex assay; ELISA assay was further applied for validation. RESULTS The levels of cytokines were mostly increased (TNF-α, IL-1α, IL-1ß, IL-6, IL-8, IL-12 P70, IL-13, IFN-γ, and MIP-1α) in DED patients compared with normal participants. And the levels of TNF-α, IL-6, IL-8, and IL-12P70 were significantly elevated in tears of the patient groups compared to tears of participants in the normal group (P<0.05). Statistical differences were also observed among the patient groups (SS-ATD, NSS-ATD, and MGD) for the level of IL-8 and TNF-α. The results of ELISA assay demonstrated the consistence with Luminex assay, confirming the practicality of Luminex technology for the analysis of multiple cytokines in DED patient tears. CONCLUSIONS The levels of inflammatory cytokines were mostly elevated in DED patients, and statistical differences of some cytokines were also found between SS-ATD, NSS-ATD, and MGD groups, suggesting that inflammatory cytokines could be potential supplements for the diagnosis of DED subclasses and therapeutic targets for DED patients.

Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers.

The goal of this work was to investigate the tumor mutational burden (TMB) in Chinese patients with gynecologic cancer. In total, 117 patients with gynecologic cancers were included in this study. Both tumor DNA and paired blood cell genomic DNA were isolated from formalin-fixed paraffin-embedded (FFPE) specimens and blood samples, and next-generation sequencing was performed to identify somatic mutations. TP53, PTEN, ARID1A, and PIK3CA alterations were significantly different in various types of gynecologic cancers (p = 0.001, 1.15E-07, 0.004, and 0.009, respectively). The median TMB of all 117 gynecologic tumor specimens was 0.37 mutations/Mb, with a range of 0-41.45 mutations/Mb. Despite the lack of significant difference, endometrial cancer cases had a higher median TMB than cervical and ovarian cancer cases. Younger gynecologic cancer patients (age <40 years) had a significantly lower TMB than older patients (age ≥40 years) (p = 0.04). In addition, TMB was significantly increased with increasing clinical stage of disease (p = 0.001). PTEN alterations were commonly observed in patients with a moderate to high TMB (n = 8, 38.10%, p = 9.95E-04). Although limited by sample size, all of the patients with TSC2 (n = 3, p = 3.83E-11) or POLE (n = 2, p = 0.005) mutations had a moderate to high TMB. Further large-scale, prospective studies are needed to validate our findings.