Systemic Importance and Risk Characteristics of Banks Based on a Multi-Layer Financial Network Analysis.

Domestic and international risk shocks have greatly increased the demand for systemic risk management in China. This paper estimates China's multi-layer financial network based on multiple financial relationships among banks, assets, and firms, using China's banking system data in 2021. An improved PageRank algorithm is proposed to identify systemically important banks and other economic sectors, and a stress test is conducted. This study finds that China's multi-layer financial network is sparse, and the distribution of transactions across financial markets is uneven. Regulatory authorities should support economic recovery and adjust the money supply, while banks should differentiate competition and manage risks better. Based on the PageRank index, this paper assesses the systemic importance of large commercial banks from the perspective of network structure, emphasizing the role of banks' transaction behavior and market participation. Different industries and asset classes are also assessed, suggesting that increased attention should be paid to industry risks and regulatory oversight of bank investments. Finally, stress tests confirm that the improved PageRank algorithm is applicable within the multi-layer financial network, reinforcing the need for prudential supervision of the banking system and revealing that the degree of transaction concentration will affect the systemic importance of financial institutions.

Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.

Treatment of giant neurofibromas in extremities and trunk wall of neurofibromatosis type 1 patients: a Chinese 12-year single-institution experience.

BACKGROUNDS: Giant neurofibromas occurring in individuals diagnosed with neurofibromatosis type 1 (NF1) often result in considerable disfigurement, functional impairment, and diminished quality of life. Although debulking surgery poses inherent risks of complications, it remains the most efficacious approach to address these issues. The primary objective of this study was to share our surgical experience with giant neurofibromas in the extremities and trunk wall of NF1 patients which may help surgeons to minimize intraoperative bleeding and facilitate tumor excision. METHODS: A retrospective review was conducted at a single center, encompassing 36 NF1 patients with giant neurofibromas in the extremities and trunk wall who underwent debulking surgery from July 2010 to July 2022. RESULTS: Twenty-one male and fifteen female NF1 patients who received one to four surgical interventions were evaluated. The average age at the time of surgery was 17.8 years. The median follow-up time was 52 months. Our findings revealed relatively low rates of complications and recurrence. Notably, patients expressed satisfaction with both the aesthetic and functional results. CONCLUSIONS: Debulking surgery of giant neurofibromas in the extremities and trunk wall of NF1 patients can effectively reduce the tumor burden, leading to improvements in both the appearance and function.

De novo urinary incontinence and lower urinary tract symptoms after colpocleisis: A single-center prospective study.

Background: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now. Purpose: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms. Methods: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients' satisfaction. Results: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory -6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P < 0.001). The patients' quality of life indicated by Urinary Distress Inventory-6 and Urinary Impact Questionnaire-7 scores were significantly improved postoperatively (26.27 vs. 13.39, and 19.13 vs. 6.05, P < 0.05). Conclusion: The incidence of de novo urinary incontinence after colpocleisis was very low. Patients' quality of life, and low urinary tract symptoms were significantly improved after colpocleisis.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia.

Background: Both the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group. Results: The NN group's placental weight differed significantly from that of the other groups. The structure of NN group's placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn't be discounted. Conclusion: In diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn't be ignored because of their tight relationships.

Developmental Trajectories of Mental Health in Chinese Early Adolescents: School Climate and Future Orientation as Predictors.

There is growing support for the dual-continua model of mental health, which emphasizes psychopathology and well-being as related but distinct dimensions. Yet, little is known about how these dimensions co-develop from childhood to early adolescence and what factors predict their different trajectories. The current study aimed to identify distinct patterns of mental health in Chinese early adolescents, focusing on both psychopathological symptoms (i.e., depressive symptoms and self-harm behaviors) and subjective well-being (i.e., life satisfaction and affect balance). This study also examined the contributions of school climate and future orientation to these trajectories. A total of 1,057 students (Mage = 11.88, SDage = 1.67; 62.1% boys) completed four assessments over two years, with six-month intervals. Using parallel-process latent class growth modeling, we identified four groups: Flourishing (32.5%), Languishing (43.8%), Troubled with Stable Depressive Symptoms (16.1%), and Troubled with Increasing Self-Harm Risk (7.6%). Furthermore, school climate and future orientation contributed to adolescents' membership in these trajectories, either independently or jointly. Specifically, higher levels of future orientation combined with higher school climate were associated with a lower likelihood of belonging to the Troubled with Increasing Self-Harm Risk trajectory, compared to the Flourishing group. Our findings identified four distinct mental health trajectories consistent with the dual-continua model, and demonstrated that the development of psychopathology and well-being were not always inversely related (e.g., the Languishing group). Adolescents with unique developmental profiles may benefit from tailored intervention strategies that build on the personal and environmental assets of the adolescent.

Macrophage Migration Inhibitory Factor as a Potential Plasma Biomarker of Cognitive Impairment in Cerebral Small Vessel Disease.

As the pathogenesis of cerebral small vessel disease with cognitive impairment (CSVD-CI) remains unclear, identifying effective biomarkers can contribute to the clinical management of CSVD-CI. This study recruited 54 healthy controls (HCs), 60 CSVD-CI patients, and 57 CSVD cognitively normal (CSVD-CN) patients. All participants underwent neuropsychological assessments and multimodal magnetic resonance imaging. Macrophage migration inhibitory factors (MIFs) were assessed in plasma. The least absolute shrinkage and selection operator model was used to determine a composite marker. Compared with HCs or CSVD-CN patients, CSVD-CI patients had significantly increased plasma MIF levels. In CSVD-CI patients, plasma MIF levels were significantly correlated with multiple cognitive assessment scores, plasma levels of blood-brain barrier (BBB)-related indices, white matter hyperintensity Fazekas scores, and the mean amplitude of low-frequency fluctuation in the right superior temporal gyrus. Higher plasma MIF levels were significantly associated with worse global cognition and information processing speed in CSVD-CI patients. The composite marker (including plasma MIF) distinguished CSVD-CI patients from CSVD-CN and HCs with >80% accuracy. Meta-analysis indicated that blood MIF levels were significantly increased in CSVD-CI patients. In conclusion, plasma MIF is a potential biomarker for early identification of CSVD-CI. Plasma MIF may play a role in cognitive decline in CSVD through BBB dysfunction and changes in white matter hyperintensity and brain activity.

Acute puerperal uterine inversion with successful manual transvaginal repositioning: A case report.

RATIONALE: Uterine inversion is a rare medical condition that is categorized as puerperal and nonpuerperal. Repositioning of uterine involution can be done manually or surgically, the latter of which involves abdominal manipulation and disruption of the integrity of the uterine wall, which can lead to complications for the patient in subsequent pregnancies, such as uterine rupture. PATIENT CONCERNS: We report a case of acute puerperal uterine inversion that was manually repositioned transvaginally. An ultrasonogram and reset schematic were also presented. A 23-year-old woman (gravida 1 para 0) was admitted to the hospital with a full-term pregnancy. DIAGNOSES: In the postpartum period, we found placental adhesions and uterine inversion into the uterine cavity, which was confirmed by bedside ultrasound. INTERVENTIONS AND OUTCOMES: We administered analgesic, relieving uterine spasms, and antishock therapy along with manual stripping of the placenta and ultrasound-guided uterine repositioning. After successful repositioning the patient vaginal bleeding decreased rapidly and she was discharged 3 days after delivery. LESSONS: Early recognition, antishock therapy and prompt repositioning are key in the management of puerperal uterine inversion. We hope that this case will enable clinicians to better visualize the ultrasound imaging of uterine inversion and the process of manual repositioning.

Circ-EIF3I Promotes Hepatocellular Carcinoma Progression Through Modulating miR-361-3p/DUSP2 Axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.

Successful diagnosis of asymptomatic choriocarcinoma by ultrasonography during a viable pregnancy: A rare case report.

BACKGROUND: Gestational choriocarcinoma occurs very rare in conjunction with pregnancy and it is camouflage for diagnosis. METHODS: We present a rare case of asymptomatic choriocarcinoma in a viable pregnancy that was successfully diagnosed by ultrasonography and had timely treatment. RESULTS: According to the ultrasonography, early diagnosis and treatment monitoring of choriocarcinoma during a viable pregnancy was administered and the newborn was discharged. CONCLUSION: Choriocarcinoma in pregnancy is camouflaged, and its clinical presentation varies widely. Despite an asymptomatic status, metastasis can occur, and ultrasonography is important for early diagnosis and treatment monitoring.

The epidemiology of pregnancy loss: global burden, variable risk factors, and predictions.

STUDY QUESTION: Is the incidence of pregnancy loss correlated with various geographic, socio-demographic, and age stratifications at the societal and national levels, and what are the risk factors associated with pregnancy loss at the individual level? SUMMARY ANSWER: The epidemiological trends and disease burden of pregnancy loss were correlated with various geographic, socio-demographic, and age stratifications, and we identified that poor health condition, smoking, sedentary behaviour, lower educational level, and lower maternal birth weight may significantly increase the risk of pregnancy loss. WHAT IS KNOWN ALREADY: Several studies have used national, regional, or single-centre data to describe trends in the burden of pregnancy loss, and previous observational studies have identified some variable factors possibly associated with pregnancy loss. However, a comprehensive analysis of global trends and predictions of pregnancy loss are lacking, and the conclusions have been inconsistent. STUDY DESIGN, SIZE, DURATION: We have utilized the data from Global Burden of Disease (GBD) 2019 to provide an overview of the trends in pregnancy loss in 204 countries and regions worldwide from 1990 to 2019, and have made a forecast for the next 10 years. Moreover, we applied a variety of statistical genetics methods to analyse 34 239 pregnancy loss and 89 340 non-pregnancy loss cases from the FinnGen consortium to comprehensively assess the bidirectional causality of variable factors with pregnancy loss from an individual perspective. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed trends in the incidence, disability-adjusted life years (DALYs), and maternal mortality of pregnancy loss at global, regional, national, socio-demographic index (SDI), and age levels. The autoregressive integrated moving average (ARIMA) model was used to predict trends by 2030. Finally, we used two-sample Mendelian randomization (MR) and multivariate MR (MVMR) analyses to explore the relationship between the pregnancy loss and variables closely related to physical condition, physical activity, lifestyle, sleep conditions, basic conditions. MAIN RESULTS AND THE ROLE OF CHANCE: In 2019, there were approximately 42.39 million cases of pregnancy loss worldwide. Globally, the incidence, DALYs, and mortality of pregnancy loss showed a decreasing trend between 1990 and 2019, although the number was increasing in some countries. The age-standardized incidence, DALYs, and mortality rate were negatively correlated with SDI level and show a further decline by 2030. Based on MR analyses, we confirmed that genetically predicted overall health rating (inverse-variance weighted (IVW) odds ratio (OR), 1.68; 95% CI, 1.34-2.13; P = 5.10 × 10-6), smoking initiation (IVW OR, 1.26; 95% CI, 1.16-1.38; P = 1.90 × 10-9), sedentary behaviour (IVW OR, 1.56; 95% CI, 1.20-2.01; P = 2.76 × 10-5), educational level (IVW OR, 0.64; 95% CI, 0.55-0.73; P = 6.56 × 10-10), and maternal birth weight (IVW OR, 0.70; 95% CI, 0.58-0.85; P = 2.98 × 10-4) were significantly related to the risk of pregnancy loss, whereas body mass index (IVW OR, 1.10; 95% CI, 1.03-1.17; P = 5.31 × 10-3), alcohol consumption (IVW OR, 1.74; 95% CI, 1.03-2.95; P = 0.04), insomnia (IVW OR, 1.66; 95% CI, 1.14-2.42; P = 7.00 × 10-3), and moderate-to-vigorous physical activity (IVW OR, 0.59; 95% CI, 0.37-0.95; P = 2.85 × 10-2) were suggestively associated with the risk of pregnancy loss. These results were supported by sensitivity and directional analyses. LIMITATIONS, REASONS FOR CAUTION: Despite efforts to standardize GBD data from all over the world, uncertainties in data quality control regarding ascertainment of pregnancy loss, medical care accessibility, cultural differences, and socioeconomic status still exist. Furthermore, the population in the MRstudy was limited to Europeans, which means that the results may not be extrapolated to people of other origins. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides for the first time an overview of the epidemiological trends and disease burden of pregnancy loss related with SDI, region, country, and age, and predicts changes in future trends up to 2030. In addition, findings support that genetic susceptibility, smoking, health condition, and sedentary behaviour may be powerful indicators of an increased risk of pregnancy loss. These results would be beneficial for policy makers of different countries and regions to improve prevention implementation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants 2021JH2/10300093, from the Science and Technology Projects of Liaoning Province, China. All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis.

OBJECTIVES: To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations. METHODS: Patients received oral infigratinib 125 mg (IN cohort, n = 125) or oral larotrectinib (LB cohort, n = 105) until unacceptable toxicity or disease progression. RESULTS: Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5-6.25] months vs. 5.5 [6-5.25] months, p < 0.0001). Patients with partial responses (p = 0.0424) and overall survival (p = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (p = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (p = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (p = 0.048). CONCLUSIONS: Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.

A case report of single umbilical artery combined with fetal bladder exstrophy in singleton pregnancy and related literature review.

BACKGROUND: According to prenatal ultrasonographic studies, single umbilical artery may be present alone or in association with other fetal abnormalities. So far, the exact pathogenesis of bladder exstrophy is unclear. Some scholars believe that bladder exstrophy and cloacal exstrophy should be regarded as a disease spectrum to explore their pathogenesis. If bladder exstrophy and cloacal exstrophy are regarded as the same disease spectrum, then we can speculate that the single umbilical artery should have the probability of being accompanied by bladder exstrophy at the same time. CASE PRESENTATION: For the first time, we report a rare case of fetal bladder exstrophy with single umbilical artery in single pregnancy. This patient underwent targeted color Doppler ultrasound at 26 weeks of pregnancy which first suspected bladder exstrophy with single umbilical artery and fetal MRI for diagnosis at 38 + 3 weeks of pregnancy which confirmed the suspicion. After the diagnosis was confirmed, the patient was scheduled for a multidisciplinary discussion. Ultimately the patient opted for induced fetal demise at 38 + 5 weeks of pregnancy and the physical appearance of the fetal demise affirmed previous ultrasound and MRI examination results. CONCLUSIONS: Our report is the first finding of single umbilical artery combined with bladder exstrophy in a singleton pregnancy. Accordingly, our case enhances the evidence that cloacal exstrophy and bladder exstrophy should be treated as the same disease spectrum. In addition, we conducted a literature review on the diagnostic progress of single umbilical artery combined with bladder exstrophy, hoping to provide useful references for the diagnosis of this disease.

Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up.

Although transvaginal mesh (TVM) repair is no longer used in some countries, long-term outcomes after TVM surgery are of great importance globally. However, reports with follow-up >10 years are limited. Thus, this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up. Women with stage III-IV symptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital. The main outcome measure was symptomatic failure. Secondary outcomes included anatomic failure, recurrence, patient satisfaction, complications, and reoperation. The Kaplan-Meier curve was used to estimate the cumulative failure rate. Of the 121 patients enrolled in the study, 103 (85.1%) completed a median follow-up of 11 years. The estimated probability rates of symptomatic and anatomic failure were 17.6% and 8.8% in 11 years, respectively. The estimated incidence of symptomatic failure increased by 8.2% between 5 and 11 years; however, the corresponding rate for anatomic failure was 3.7%. The most common complication was vaginal mesh exposure, and its estimated probability increased from 19.3% to 28.4% from 5 to 11 years, respectively. Office trimming resolved 80.0% of vaginal exposures. These patients did not report decreased overall satisfaction. Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room (5.8% by 11 years) had lower satisfaction rates (P<0.01) and were defined as having severe mesh exposure. The rates of postoperative pain, reoperation, and Patient Global Impression of Improvement ⩾2 were 2.5%, 3.3%, and 94.2%, respectively. The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall. Vaginal mesh exposure was common in women who were largely not sexually active; however, 80% of the cases could be managed in the outpatient clinic, which did not affect patient satisfaction.

The Impact of Imaging-Diagnosed Sarcopenia on Long-term Prognosis After Curative Resection for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Recent research suggests that sarcopenia potentially influences the long-term postoperative prognosis of malignant tumors. Thus, the primary objective of this study was to investigate the impact of imaging-diagnosed sarcopenia on the long-term prognosis of hepatocellular carcinoma (HCC) patients after curative resection. METHODS: In our approach, all studies incorporated in this study employed Cox proportional hazards models with multivariable adjusted hazard ratios. The meta-analysis was performed using R statistical software. The primary outcomes were quantified using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: This study analyzed 30 studies, involving 7352 HCC patients after curative resection (2695 in the sarcopenia group and 4657 in the non-sarcopenia group). The meta-analysis of 28 studies indicated that patients in the sarcopenia group demonstrated notably inferior overall survival (OS) compared with the non-sarcopenia group (HR=2.20; 95% CI, 1.88-2.58; p < 0.01). Similarly, sarcopenia exhibits a significant association with poor recurrence-free survival (RFS) and disease-free survival (DFS) based on 16 and 6 studies (HR=1.50; 95% CI, 1.39-1.63; p < 0.01 and HR=1.96; 95% CI, 1.83-2.10; p < 0.01, respectively). CONCLUSION: In conclusion, imaging-diagnosed sarcopenia adversely affects the long-term prognosis, including OS, RFS, and DFS, in HCC patients after curative resection. The findings hold considerable importance in guiding comprehensive healthcare procedures for HCC patients after surgery.

Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis

Abstract Objectives To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations. Methods Patients received oral infigratinib 125 mg (IN cohort, n = 125) or oral larotrectinib (LB cohort, n = 105) until unacceptable toxicity or disease progression. Results Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5-6.25] months vs. 5.5 [6-5.25] months, p < 0.0001). Patients with partial responses (p = 0.0424) and overall survival (p = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (p = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (p = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (p = 0.048). Conclusions Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.

Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils.

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors.

Outer membrane vesicles mediating horizontal transfer of the epidemic blaOXA-232 carbapenemase gene among Enterobacterales.

OXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The blaOXA-232 gene is located on a 6-kb non-conjugative ColKP3-type plasmid, while the dissemination of blaOXA-232 into different Enterobacterales species and the polyclonal dissemination of OXA-232-producing K. pneumoniae revealed the horizontal transfer of blaOXA-232. However, it's still unclear how this non-conjugative ColKP3 plasmid could facilitate the mobilization of blaOXA-232. Here, we observed the in vivo intraspecies transfer of blaOXA-232 during a nosocomial outbreak of OXA-232-producing K. pneumoniae. We demonstrated the presence of ColKP3 OXA-232 plasmid in the outer membrane vesicles (OMVs) derived from clinical isolates, and OMVs could facilitate the horizontal transfer of blaOXA-232 among Enterobacterales. In contrast, for the most prevalent carbapenemase genes, including blaKPC-2 and blaNDM-1, though the presence of carbapenemase genes and plasmid backbones in the vesicular lumen was observed, OMVs couldn't promote effective transformation, probably due to the low copy number of plasmids in clinical isolates and the low number of plasmids loaded into vesicles. Conjugation assay revealed that the epidemic IncX3 NDM-1 and IncFII(pHN7A8)/IncR KPC-2 plasmids were conjugative and could be horizontally transferred via independent conjugation or with the help of a co-existent conjugative plasmid. For the large-size and low-copy number conjugative plasmids carrying carbapenemase genes, OMVs-mediated gene exchange may only serve as an alternative pathway for horizontal transfer. In conclusion, diverse mobilization strategies were employed by plasmids harboring carbapenemase genes, and plasmids display a proper choice of mobility pathway due to their individual properties.