Benchmarking State-of-the-Art Large Language Models for Migraine Patient Education: Performance Comparison of Responses to Common Queries.

This study assessed the potential of large language models (OpenAI's ChatGPT 3.5 and 4.0, Google Bard, Meta Llama2, and Anthropic Claude2) in addressing 30 common migraine-related queries, providing a foundation to advance artificial intelligence-assisted patient education and insights for a holistic approach to migraine management.

Activity-to-sedentary ratio provides novel insight into mortality reduction among male survivors of cardiovascular disease in the United States: national health and nutrition examination survey, 2007-2014.

BACKGROUND: Lower physical activity and sedentary behavior have been identified as modifiable risk factors for cardiovascular disease (CVD). However, the quantitative, dose-response association between activity-to-sedentary ratio (ASR) and mortality is unknown. METHODS: Prospective cohort studies with participants 50 to 80 years that reported the association between recreational physical activity, sedentary behavior, and all-cause mortality were included from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) and followed through December 31, 2015. Cox or Weibull regression models and restricted cubic splines were used to determine the association between ASR and all-cause mortality. RESULTS: Sixty deaths occurred among 498 CVD survivors, with a median of 56 months of follow-up. After accounting for all covariates, CVD survivors with an ASR between 0.21 and 0.57 (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and those with an ASR more than 0.57 (HR, 0.40; 95% CI, 0.20-0.81) were at significantly lower risk for mortality than participants with an ASR <  0.21. Moreover, a nonlinear negative association and an L-shaped association were observed for the level of ASR with risk of mortality among CVD survivors (P for nonlinearity = 0.004). What's more, adjusting for covariates, a statistically significant interaction (P for interaction = 0.016) between sex and ASR, an increase of ASR more than and equal to 0.18 was associated with a lower risk of mortality among males (HR, 0.23; 95% CI, 0.12-0.46). CONCLUSIONS: An negative correlation between ASR and mortality in CVD survivors, especially in males when ASR is more than 0.18. Our novel findings provide further insights into easing the global burden of deaths.

Lower uric acid level may be associated with hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND: Previous studies have shown that uric acid (UA) is a powerful water-soluble antioxidant and free radical scavenger for humans. However, the relationship between serum uric acid (SUA) and hemorrhagic transformation (HT) is still controversial. To address this challenge, we aimed to explore the association between serum UA and HT in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: A retrospective analysis was conducted in patients with anterior circulation AIS who underwent IVT at Affiliated Hospital of Qingdao University from 2016 to 2021. HT was evaluated by CT or MRI within 7 days after admission. Baseline demographic, clinical, and laboratory data were compared between the HT and non-HT groups, and between different types of HT groups which were documented according to the European Cooperative Acute Stroke Study III Classification (ECASS III). RESULTS: A total of 727 AIS patients were enrolled, including 112 patients who experienced HT (HT group) and 615 patients who did not experience HT (non-HT group). Patients with HT had significantly lower UA levels compared to those without HT (253.65 ± 97.75 vs 315.97 ± 96.42, p < 0.001); however, there was no significant difference for UA levels in different types of HT (p = 0.907). After adjusting confounders, patients in the fourth UA quartile showed a significant decrease in HT compared with those in the first quartile (OR 0.266, 95% CI 0.107-0.661, p = 0.006). The best cutoff value was identified as 218.5 µmol/L after analysis. CONCLUSIONS: These findings suggest that low levels of UA may be associated with HT after IVT.

Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424-5p/suppressor of zeste 12 pathway.

Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424-5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424-5p locus. Furthermore, miR-424-5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424-5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424-5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

A prospective randomized controlled trial comparing two different treatments of intrauterine adhesions.

RESEARCH QUESTION: Intrauterine adhesions (IUA) are primarily caused by trauma to the endometrium, and hysteroscopy is presently the main treatment for IUA. However, high rates of post-operative adhesion re-formation remain a problem. In this study, the combination of an intrauterine device (IUD) with a Foley catheter and the balloon uterine stent were investigated to evaluate their efficacy in preventing adhesion re-formation and the subsequent reproductive outcomes in patients with moderate to severe adhesions. DESIGN: A prospective randomized controlled study was conducted in a university-affiliated hospital. A total of 171 women with Asherman's syndrome were initially recruited between August 2016 and December 2017 and were randomized to undergo either balloon uterine stent insertion or placement of a contraceptive IUD plus a Foley catheter after hysteroscopic adhesiolysis. Reduction of adhesion scores, incidence of adhesion re-formation, changes in menstrual flow and reproductive outcomes were analysed. RESULTS: A total of 118 participants were eligible for analysis. The American Fertility Society (AFS) scores were not significantly different between groups before hysteroscopic adhesiolysis. At the second-look hysteroscopy, the AFS scores and adhesion recurrence rates were significantly higher in the balloon uterine stent group compared with the combination group (P < 0.01 and P = 0.024, respectively). There were no statistically significant differences in pregnancy and live birth rates between the two groups. CONCLUSIONS: The combination of an IUD and a Foley balloon catheter had better efficacy in preventing adhesion re-formation than the balloon uterine stent alone; however, it did not produce better reproductive outcomes.

Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial.

BACKGROUND: Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. OBJECTIVE: The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. STUDY DESIGN: The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. RESULTS: Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). CONCLUSION: For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

Hesperetin ameliorates lipopolysaccharide-induced acute lung injury via the miR-410/SOX18 axis.

Hesperetin (Hesp), a dihydroflavone, has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and antitumor effects, as well as cardiovascular protection. It also has protective effects against acute lung injury (ALI); however, the exact mechanism remains unclear. In the present study, the protective effects and mechanism of Hesp in the lungs were investigated. Hematoxylin and eosin staining was used to examine pathological changes in the lungs. Enzyme-linked immunosorbent assay was used to detect proinflammatory cytokine levels. In addition, reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to observe the transcription and translation changes in the related genes, respectively. The results indicate that Hesp not only improves histopathological changes in the lungs but decreases the wet/dry ratio. In addition, total cell counts and the number of neutrophils and macrophages were lower in the bronchoalveolar fluid after Hesp treatment, consistent with the change in proinflammatory cytokine levels. MicroRNA-410 (miR-410) levels were significantly lower in the lung tissues of ALI mice and were reversed after Hesp treatment. Furthermore, miR-410 overexpression due to injection with agomiR-410 produced similar protective effects as Hesp. However, blocking miR-410 inhibited the protective effects of Hesp in the lungs of ALI mice. In addition, miR-410 has been shown to target the inhibition of sex determining region Y-box 18 (SOX18), indicating that Hesp might alleviate inflammatory secretion by blocking the miR-410/SOX18 axis. Thus, Hesp might be a potential agent for the treatment of ALI.

Comparison of laparoscopic and open radical hysterectomy in cervical cancer patients with tumor size ≤2 cm.

OBJECTIVE: There is recent evidence that demonstrates worse oncologic outcomes associated with minimally invasive radical hysterectomy when compared with open radical hysterectomy, particularly in patients with tumors >2 cm. The aim of our study was to retrospectively evaluate the oncological outcomes between laparoscopic and open radical hysterectomy in International Federation of Gynecology and Obstetrics(FIGO) 2009 stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm. METHODS: A retrospective review of medical records was performed to identify patients who underwent either laparoscopic or open radical hysterectomy during January 2010 and December 2018. Inclusion criteria were: (1) histologically confirmed cervical cancer including all histological types; (2) FIGO 2009 stage IB1; (3) tumor size ≤2 cm (determined by pelvic examination, magnetic resonance imaging or transvaginal ultrasound); (4) had undergone radical hysterectomy (type II or III) with pelvic and/or para-aortic lymphadenectomy as primary surgical treatment; (5) had follow-up information. Patients with FIGO 2009 stage IA1 or IA2, tumor size >2 cm, or who received neo-adjuvant chemotherapy before surgery, those with cervical cancer incidentally found after simple hysterectomy, or with insufficient data were excluded. Concurrent comparison between the laparoscopic and open cohorts was made for disease-free survival and overall survival. RESULTS: A total of 325 cervical cancer patients were included; of these, 129 patients underwent laparoscopic surgery and 196 patients had open surgery. The median follow-up times were 51.8 months (range 2-115) for laparoscopic surgery and 49.5 months (range 3-108) for open surgery. Patients in the laparoscopic group had significantly worse 5 year disease-free survival than those in the open group (90.4% vs 97.7%; p=0.02). There was no significant difference in 5 year overall survival between groups (96.9% vs 99.4%, p=0.33). The Cox proportional hazards regression analysis indicated that laparoscopic surgery was associated with lower disease-free survival compared with open surgery (adjusted hazard ratio 4.64, 95% CI 1.26 to 17.06; p=0.02). In patients with non-squamous cell carcinoma or with grade II-III, laparoscopic surgery had a significantly worse 5 year disease-free survival compared with the open surgery group (74% vs 100%, p=0.01, and 88.8% vs 98.0%, p=0.02, respectively). CONCLUSION: Laparoscopic radical hysterectomy was associated with worse disease-free survival for stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm compared with open radical hysterectomy. Further studies may shed additional light on the impact of minimally invasive surgery in this low-risk patient population.

Involvement of miR-200b-PKCα signalling in pulmonary hypertension in cor pulmonale model.

The right ventricle (RV) enlargement and pulmonary fibrosis are involved in cor pulmonale. The role of miR-200b in cor pulmonale is less well understood. This study was designed to evaluate the regulatory roles of miR-200b in cor pulmonale. Cor pulmonary mouse model was built via monocrotaline injection of monocrotaline (MCT). The expression of miR-200b in the lungs, RV and left ventricle (LV) are using real-time polymerase chain reaction. The transthoracic echocardiography was employed to determine the effects of miR-200b mimics and Gö6976 injection on MCT mice. The protein levels of protein kinase C α (PKCα), collagen, and fibronectin in the lung, RV, and LV in the mice with and without miR-200b mimics and Gö6976 injection were evaluated using western blot. The expression of miR-200b decreased in MCT mice, while there was no difference in LV. Both the miR-200b mimics and Gö6976 injection reversed the muscularization in the pulmonary artery, reversed RV hypertrophy, reduced RV systolic pressure, wall thickness and pulmonary fibrosis. The injection of miR-200b can reduce the PKCα expression in the lung, RV, and LV. This study confirmed the down-regulation of miR-200b in cor pulmonale. The reverse effects of miR-200b in the present study may provide a potential tool for cor pulmonary treatment.

Making Choices: Ethical Decisions in a Global Context.

The changing milieu of research--increasingly global, interdisciplinary and collaborative--prompts greater emphasis on cultural context and upon partnership with international scholars and diverse community groups. Ethics training, however, tends to ignore the cross-cultural challenges of making ethical choices. This paper confronts those challenges by presenting a new curricular model developed by an international team. It examines ethics across a very broad range of situations, using case studies and employing the perspectives of social science, humanities and the sciences. The course has been developed and taught in a highly collaborative way, involving researchers and students at Zhejiang University, the Indian Institute of Technology, Bombay and Brown University. The article presents the curricular modules of the course, learning outcomes, an assessment framework developed for the project, and a discussion of evaluation findings.

Cushing's syndrome secondary to ectopic ACTH secretion from carcinoid tumor within an ovarian mature teratoma: a case report and review of the literature.

A 46-year-old woman with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion caused by primary ovarian mature teratoma with carcinoid components was presented in our case. The patient manifested sustained hypercortisolemia without circadian rhythm and a lack of suppression of either low-dose dexamethasone suppression test (LDDST) or high-dose dexamethasone suppression test (HDDST). There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumors led to sharp reduction of serum ACTH and cortisol concentrations. Immunohistochemistry showed positivity in CgA, Syn, CK, NSE. To the best of our knowledge, there are rare reports of an ACTH-secreting carcinoid components located in an ovarian mature teratoma, and bilateral ovarian mature teratoma makes it rarer.

Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype.

JOURNAL/nrgr/04.03/01300535-202419110-00029/figure1/v/2024-03-08T184507Z/r/image-tiff Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE-/- mice. However, little is known about the role of lnc_000048 in classically activated macrophage (M1) polarization. In this study, we established THP-1-derived testing state macrophages (M0), M1 macrophages, and alternately activated macrophages (M2). Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages. Flow cytometry was used to detect phenotypic proteins (CD11b, CD38, CD80). We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048. Flow cytometry, western blot, and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response, while over-expression of lnc_000048 led to the opposite effect. Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization. Moreover, catRAPID prediction, RNA-pull down, and mass spectrometry were used to identify and screen the protein kinase RNA-activated (PKR), then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR. Immunofluorescence (IF)-RNA fluorescence in situ hybridization (FISH) double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage. We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation, leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression. Taken together, these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

Embolic stroke of undetermined source: Focusing on atrial cardiopathy and patent foramen ovale.

BACKGROUND: Atrial cardiopathy(AC) and patent foramen ovale (PFO) are two etiologies of embolic strokes of undetermined source (ESUS). We aimed to explore the relationship between them in ESUS. METHODS: A total of 1146 participants were included from January 2019 to June 2022, which included the ESUS group and non-embolic stroke which includes LAA(large arterial atherosclerosis) + SAO(small artery occlusion) group. AC was defined as the presence of at least one of the following: PTFV1(P-wave terminal force in lead V1) > 4000 µV*ms in the electrocardiograms, NT-proBNP(N-terminal probrain natriuretic peptide) > 250 pg/mL in laboratory tests or LAD(left atrial diameter) > 3.8 cm for women and > 4.0 cm for men in cardiac ultrasound. The presence of PFO was assessed by transthoracic echocardiography, transcranial Doppler ultrasound, transesophageal echocardiography or cardiac MRI. PFO was considered pathogenic if the RoPE score was 7 to 10. RESULTS: The prevalence of AC and PFO was higher in the ESUS group than the LAA + SAO group. The prevalence of AC was lower in ESUS patients with pathogenic PFO (37.9%) than those without PFO (68.4%) and with incidental PFO (64.0%) (p = 0.006). The prevalence of pathogenic PFO was lower in ESUS patients with AC than those without AC (6.0% vs. 17.8%, p = 0.006). The AUC(area under the curve) of PTFV1 for predicting ESUS was 0.724 [95%CI (0.686-0.762), p < 0.05)], indicating that PTFV1 the most valuable AC biomarker. CONCLUSIONS: The prevalence of AC is inversely related to the prevalence of pathogenic PFO in ESUS patients. PTFV1 was the most valuable index to predict ESUS among the AC biomarkers.

Survivin status affects prognosis and chemosensitivity in epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to explore the clinical significance of survivin expression in epithelial ovarian cancer (EOC) and the effect of survivin small hairpin RNA (shRNA) on survivin expression, apoptosis, and chemosensitivity in the human ovarian cancer cell line OVCAR3. METHODS: A retrospective review of 90 consecutive EOC patients with a median follow-up time of 51 months was conducted. Survivin expression was examined by immunohistochemistry. OVCAR3 cells were transfected in vitro with survivin shRNA. Survivin mRNA expression levels were detected using reverse transcription-polymerase chain reaction. Flow cytometry was applied to determine survivin protein expression levels and cell apoptotic rates. The MTT method was used to examine the effects of survivin shRNA on chemosensitivity in OVCAR3 cells. RESULTS: Positive cytoplasmic expression of survivin was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, nonmucinous type, high grade, and recurrence. Positive survivin expression was also associated with platinum resistance (r = 0.306, P = 0.003). Statistical results indicated that FIGO stage (hazard rate = 1.649, P = 0.047) and cytoplasmic expression of survivin (hazard rate = 1.734, P = 0.010) were independent prognostic factors. Survivin mRNA and protein levels were lower in OVCAR3S (ovarian cancer cells transfected with a survivin recombinant vector) cells at 24 hours after transfection as compared with controls. The flow cytometric analysis revealed that survivin shRNA induced accumulation of cells in the G0/Gl phase, with a decrease in G2/M phase cells following 24 hours of culture as compared with a nontransfected group (P < 0.01). Furthermore, survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel 15-fold (P < 0.05), whereas it had no significant effect on cisplatin (P > 0.05). CONCLUSIONS: In addition to FIGO stage, cytoplasmic survivin protein expression is an independent molecular marker for predicting EOC prognosis. Sequence-specific shRNA targeting survivin can effectively suppress survivin expression, enhance apoptosis, and increase the sensitivity of ovarian cancer cells to paclitaxel but not to cisplatin.

[Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke].

OBJECTIVE: To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population. METHODS: A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene. RESULTS: An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01). CONCLUSION: Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.

Development of a nomogram for predicting pelvic lymph node metastasis in cervical squamous cell carcinoma.

OBJECTIVE: To develop and validate a nomogram for predicting pelvic lymph node metastasis (LNM) in cervical squamous cell carcinoma (SCC). METHODS: This was a retrospective study that included 715 patients with cervical SCC who underwent radical hysterectomy and bilateral pelvic lymphadenectomy between 2009 and 2018. Logistic regression analysis was used to identify independent risk factors for pelvic LNM. Based on these risk factors, a nomogram predicting LNM risk was constructed and internally validated using the bootstrapping resampling method. RESULTS: The rate of LNM in FIGO (the International Federation of Gynecology & Obstetrics) Stage IA2-IIA2 cervical SCC was 24.2%. In multivariate analysis, FIGO Stage II, moderately differentiated or poorly differentiated histology, abnormally elevated serum SCC-antigen, and triglyceride were identified as independent risk factors for LNM. Tumor size greater than 2 cm and parametrial involvement had borderline significance. Ultimately, the nomogram contained the six variables mentioned above, showing positive calibration and positive discrimination. The area under the receiver operating characteristic curvewas 0.827 and the bootstrap-validated C-index was 0.827. The Youden index of this paper was 0.540. CONCLUSIONS: We developed and validated a nomogram to predict pelvic LNM in SCC based on clinical data, which can help physicians develop an optimal treatment strategy.

Metagenomic next-generation sequencing of bronchoalveolar lavage fluid in non-severe and severe pneumonia patients.

Metagenomic next-generation sequencing (mNGS) is widely used as a more promising technology than conventional tests. However, its clinical utility in the context of bronchoalveolar lavage fluid (BALF) samples for discriminating between non-severe and severe pneumonia is not well established. Thus, this study aimed to investigate the diagnostic performance of mNGS on BALF samples from 100 individuals suspected of pneumonia, and compared it with conventional microbiological tests (CMT) of BALF samples and the final clinical diagnosis. Twenty-seven cases of non-severe pneumonia and 73 cases of severe pneumonia patients were finally clinically diagnosed. Among 100 cases, diagnostic performance of mNGS and culture showed a significant difference; 65 cases had the same sample types, of which 25 cases were diagnosed as positive by mNGS only (38.46%) and 1 was diagnosed as positive by culture only (1.54%). Moreover, 24 cases were diagnosed positive in both mNGS and culture (36.92%) and 15 cases tested negative in both mNGS and culture (23.08%). Among 35 cases, 28 out of 35 cases were diagnosed as positive by mNGS, while only 4 out of 35 cases were diagnosed as positive by the indirect immunofluorescence method (IIFT). In addition, the positive rate of mNGS was higher than that of culture in cases regardless of prior antibiotic exposure. Mixed pathogens were found to be significantly more prevalent in severe pneumonia patients than in non-severe pneumonia patients. Importantly, among 38 cases who were diagnosed solely by mNGS, 25 patients experienced an improved outcome after physicians changed the therapy according to the mNGS results. In conclusion, the results showed that mNGS of BALF represents a potentially effective tool for detection of mixed pathogens in severe pneumonia.

Interactive effect between sleep and exercise on depressive symptoms in Chinese adolescents.

Objectives: The study aimed to investigate the effects of sleep and exercise, individually and jointly, on depressive symptoms in Chinese adolescents. Methods: Cluster sampling was used to conduct a cross-sectional, electronic survey among 11,563 students from five primary and high schools in Sichuan Province in Western China. The questionnaire contained custom-designed items concerning sleep and exercise, while it used the Center for Epidemiologic Studies Depression Scale to assess depressive symptoms and the Core Self-Evaluations Scale to assess core self-evaluation. Data were analyzed using descriptive statistics and multivariate linear regression. Results: A total of 10,185 valid questionnaires were collected, corresponding to an effective response rate of 88.1%. Among the respondents in the final analysis, 5,555 (54.5%) were boys and 4,630 (45.5%) were girls, and the average age was 15.20 ± 1.72 years (range, 11-18 years). Only less than half of the respondents (4,914, 48.2%) reported insufficient sleep, while the remainder (5,271, 51.8%) had adequate sleep. Nearly one-quarter (2,250, 22.1%) reported insufficient exercise, while the remainder (7,935, 77.9%) reported adequate exercise. More than half of the respondents (5,681, 55.7%) were from vocational high school, 3,368 (33.1%) were from junior high school, 945 (9.3%) were from senior high school, and 191 (1.9%) were from primary school. The prevalence of depressive symptoms among all respondents was 29.5% (95% CI 28.7%-30.4%). When other variables were controlled, the depression score did not vary significantly with gender (B = -0.244, SE = 0.127, P = 0.054), but it decreased by 0.194 points per 1-year increase in age (B = -0.194, SE = 0.037, P < 0.001). Students getting adequate sleep had depression scores 2.614 points lower than those getting insufficient sleep (B = -2.614, SE = 0.577, P < 0.001), while students who engaged in adequate exercise had depression scores 1.779 points lower than those not exercising enough (B = -1.779, SE = 0.461, P < 0.001). The depression score decreased by 0.919 points per 1-point increase in the core self-evaluation score (B = -0.919, SE = 0.008, P < 0.001). In regression controlling for gender, age, and core self-evaluation, sleep and exercise were found to be related significantly to influence depressive symptoms (B = 0.821, SE = 0.315, P = 0.009). Conclusion: Adequate sleep and adequate exercise are individually associated with milder depressive symptoms in Chinese adolescents. Our results further highlight the need for researchers and clinicians to take into account not only the individual but also the joint effects of sleep and exercise on depression in adolescents when conducting research and designing interventions. If sleep or physical exercise has substantially reduced the risk of depressive symptoms, further reductions by improving sleep and exercise become difficult and may even have opposite effects.

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial.

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.