Impact of national drug price negotiation policy on the accessibility and utilization of PCSK9 inhibitors in China: an interrupted time series analysis.

BACKGROUND: PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China's National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. METHODS: The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. RESULTS: The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. CONCLUSIONS: The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.

Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Economic evaluation of camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma in the United States and China.

BACKGROUND: Camrelizumab combined with rivoceranib has been proven effective for treating unresectable hepatocellular carcinoma (uHCC). However, their higher prices than sorafenib could impose a substantial economic burden on patients. AIM: This study aimed to evaluate the relative cost-effectiveness of the combination of camrelizumab and rivoceranib versus sorafenib as first-line therapy for patients with uHCC from the perspective of the US and Chinese payers. METHOD: Using data from the CARES-310 trial, a partitioned survival model (PSM) was developed, considering the perspectives of the US and Chinese payers. The model employed a 15-year time horizon and a biweekly cycle. Direct medical costs and utility data were collected from previous studies and open-access databases. Primary outcomes included quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Price simulations, sensitivity analyses, and subgroup analyses were conducted. RESULTS: The ICER for the US and China was $122,388.62/QALY and $30,410.56/QALY, respectively, falling below the willingness-to-pay (WTP) thresholds of $150,000/QALY for the US and $35,898.87/QALY for China. Price simulations indicated the cost-effectiveness of camrelizumab plus rivoceranib when the price of camrelizumab (200 mg) remained below $6275.19 in the US and $558.09 in China. The primary determinant of cost-effectiveness in both regions was the cost of camrelizumab. CONCLUSION: The combination of camrelizumab and rivoceranib is a cost-effective first-line therapy for uHCC in both the US and China. Lowering their prices could significantly influence their cost-effectiveness and accessibility to patients. These findings will guide clinicians in treating uHCC and help decision-makers formulate value-based drug pricing strategies.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

Characterization and validation of TaAGL66, a gene related to fertility conversion of wheat in the presence of Aegilops kotschyi cytoplasm.

MAIN CONCLUSION: TaAGL66, a MADS-box transcription factor highly expressed in fertile anthers of KTM3315A, regulates anther and/or pollen development, as well as male fertility in wheat with Aegilops kotschyi cytoplasm. Male sterility, as a string of sophisticated biological processes in higher plants, is commonly regulated by transcription factors (TFs). Among them, MADS-box TFs are mainly participated in the processes of floral organ formation and pollen development, which are tightly related to male sterility, but they have been little studied in the reproductive development in wheat. In our study, TaAGL66, a gene that was specifically expressed in spikes and highly expressed in fertile anthers, was identified by RNA sequencing and the expression profiles data of these genes, and qRT-PCR analyses, which was localized to the nucleus. Silencing of TaAGL66 under fertility condition in KTM3315A, a thermo-sensitive male sterile line with Ae. kotschyi cytoplasm, displayed severe fertility reduction, abnormal anther dehiscence, defective pollen development, decreased viability, and low seed-setting. It can be concluded that TaAGL66 plays an important role in wheat pollen development in the presence of Ae. kotschyi cytoplasm, providing new insights into the utilization of male sterility.

Disease burden and risk factors of children aged 0-14 years in China: a retrospective study on data from the Global Burden of Disease Study 2019.

OBJECTIVES: This study aimed to analyse the current status, trends and risk factors of disease burden from 1990 to 2019 among Chinese children. DESIGN AND PARTICIPANTS: It was a retrospective study on data from the Global Burden of Disease Study 2019 (GBD 2019). Data of disease burden and risk factors were extracted from the GBD 2019. Children were divided into two groups of <5 and 5-14 years. Data were analysed using GBD results query tool, Excel and Pareto analysis. PRIMARY OUTCOME MEASURES: Disability-Adjusted Life Years (DALYs) and deaths. RESULTS: The overall disease burden for both children <5 years and those aged 5-14 years significantly decreased from 1990 to 2019. For children aged <5 years, in 2019, the leading cause of deaths and DALYs were 'neonatal disorders', and the top risk factor was 'low birth weight'. Compared with data of 1990, the ranking of causes of deaths and DALYs in 2019 saw the most significant increase for 'HIV/AIDS and sexually transmitted infections' and 'skin and subcutaneous diseases' respectively. Conversely, the ranking of deaths/DALYs causes that dropped most significantly was 'nutritional deficiencies'. For children aged 5-14, in 2019, the leading deaths and DALYs causes were 'unintentional injuries' and 'mental disorders' respectively. The top risk factors were 'alcohol use' and 'short gestation', respectively. The ranking of deaths and DALYs causes rose most significantly were 'HIV/AIDS and sexually transmitted infections' and 'neonatal disorders', respectively. Conversely, the ranking of deaths causes that dropped most significantly were 'other infectious diseases', 'enteric infections' and 'nutritional deficiencies'. For DALYs, the causes that dropped most significantly in ranking were 'other infectious diseases'. CONCLUSIONS: The disease burden of children has significantly changed from 1990 to 2019, with notable differences between children aged <5 and 5-14 years. To optimise the allocation of health resources, it is necessary to adjust management strategies based on the latest disease burden.

Aspergillus oryzae ß-D-galactosidase immobilization on glutaraldehyde pre-activated amino-functionalized magnetic mesoporous silica: Performance, characteristics, and application in the preparation of sesaminol.

Aspergillus oryzae ß-D-galactosidase (ß-Gal) efficiently hydrolyzes sesaminol triglucoside into sesaminol, which has higher biological activity. However, ß-Gal is difficult to be separate from the reaction mixture and limited by stability. To resolve these problems, ß-Gal was immobilized on amino-functionalized magnetic nanoparticles mesoporous silica pre-activated with glutaraldehyde (Fe3O4@mSiO2-ß-Gal), which was used for the first time to prepare sesaminol. Under the optimal conditions, the immobilization yield and recovered activity of ß-Gal were 57.9 ± 0.3 % and 46.5 ± 0.9 %, and the enzymatic loading was 843 ± 21 Uenzyme/gsupport. The construction of Fe3O4@mSiO2-ß-Gal was confirmed by various characterization methods, and the results indicated it was suitable for heterogeneous enzyme-catalyzed reactions. Fe3O4@mSiO2-ß-Gal was readily separable under magnetic action and displayed improved activity in extreme pH and temperature conditions. After 45 days of storage at 4 °C, the activity of Fe3O4@mSiO2-ß-Gal remained at 92.3 ± 2.8 %, which was 1.29 times than that of free enzyme, and its activity remained above 85 % after 10 cycles. Fe3O4@mSiO2-ß-Gal displayed higher affinity and catalytic efficiency. The half-life was 1.41 longer than free enzymes at 55.0 °C. Fe3O4@mSiO2-ß-Gal was employed as a catalyst to prepare sesaminol, achieving a 96.7 % conversion yield of sesaminol. The excellent stability and catalytic efficiency provide broad benefits and potential for biocatalytic industry applications.

Exercise and osteoimmunology in bone remodeling.

Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-ß, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.

Chemical Constituents and Biological Activities of Bruguiera Genus and Its Endophytes: A Review.

The genus Bruguiera, a member of the Rhizophoraceae family, is predominantly found in coastal areas as a mangrove plant, boasting a rich and diverse community of endophytes. This review systematically compiled approximately 496 compounds derived from both the Bruguiera genus and its associated endophytes, including 152 terpenoids, 17 steroids, 16 sulfides, 44 alkaloids and peptides, 66 quinones, 68 polyketides, 19 flavonoids, 38 phenylpropanoids, 54 aromatic compounds, and 22 other compounds. Among these, 201 compounds exhibited a spectrum of activities, including cytotoxicity, antimicrobial, antioxidant, anti-inflammatory, antiviral, antidiabetic, insecticidal and mosquito repellent, and enzyme inhibitory properties, etc. These findings provided promising lead compounds for drug discovery. Certain similar or identical compounds were found to be simultaneously present in both Bruguiera plants and their endophytes, and the phenomenon of their interaction relationship was discussed.

Ultrafast Multifunctional Photodetector Based on the NiAl2O4/4H-SiC Heterojunction.

Solar-blind photodetectors based on wide bandgap semiconductors have recently attracted a lot of interest. Nickel-containing spinel phase oxides, such as NiAl2O4, are stable p-type semiconductors. This paper describes a multifunctional solar-blind photodetector based on a NiAl2O4/4H-SiC heterojunction that utilizes photovoltaic effects. The position sensitivity reaches a value of 1589.7 mV/mm under 405 nm laser illumination, while the relaxation times of vertical photovoltaic (VPV) effect and lateral photovoltaic (LPV) effect under 266 nm laser illumination are only 0.32 and 0.42 µs, respectively. This junction was used to create a space optical communication system with sunlight having little effect on its optoelectronic properties. The ultrafast photovoltaic relaxation time makes NiAl2O4/4H-SiC a promising candidate for self-powered high-performance solar-blind detectors.

Patient versus physician preferences for lipid-lowering drug therapy: A discrete choice experiment.

BACKGROUND: The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors offered dyslipidemia patients an alternative to statins for lipid-lowering treatment. Understanding patient and physician preferences for lipid-lowering drugs may promote shared decision-making and improve treatment outcomes. METHODS: This study utilized an online discrete choice experiment (DCE) to assess the relative importance (RI) of six attributes related to lipid-lowering drugs, including frequency of administration, mode of administration, reduction of low-density lipoprotein cholesterol (LDL-C) level, risk of myopathy, risk of liver damage, and out-of-pocket monthly cost. Respondents were recruited from dyslipidemia patients and cardiovascular physicians in China. A mixed logit model and latent class analysis were employed to estimate the preference coefficient, marginal willingness to pay (mWTP), and RI of attributes. Ethical approval has been obtained for this study. RESULTS: A total of 708 patients and 507 physicians participated in the survey. Patients prioritized the 'risk of liver damage' (RI = 23.6%) with 'mode of administration' (RI = 19.2%) and 'frequency of administration' (RI = 18.8%) following closely. Contrarily, physicians prioritized the 'reduction of LDL-C level' (RI = 33.5%), followed by 'risk of liver damage' (RI = 26.0%) and 'risk of myopathy' (RI = 16.1%). Patients placed a higher value on 'frequency of administration' (p < .001) and 'mode of administration' (p < .001) compared to physicians, while physicians valued 'reduction of LDL-C level' (p < .001) and 'risk of myopathy' (p = .012) more than patients. Physicians exhibited higher mWTP than patients for all attributes except frequency and mode of administration. The LCA revealed three distinct patient classes: focus on oral administration, focus on hepatic safety and frequency and focus on hepatic safety and cost. Likewise, three physician classes were identified: frequency-insensitive, efficacy-focused and safety-focused. CONCLUSIONS: The preferences for lipid-lowering drug therapy differed between patients and physicians in China. Physicians should take into account patients' preferences and provide personalized treatment when they formulate lipid-lowering treatment plans. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the questionnaire design process. They engaged in a focus group discussion to determine attributes and levels and also participated in a pilot survey to assess the comprehensibility of the questionnaires. Additionally, patients were involved in the DCE survey to express their preferences. The findings of patient preference for lipid-lowering drug therapy will promote shared decision-making and optimize the treatment regimen.

Serum proteins differentially expressed in gestational diabetes mellitus assessed using isobaric tag for relative and absolute quantitation proteomics.

BACKGROUND: As a well-known fact to the public, gestational diabetes mellitus (GDM) could bring serious risks for both pregnant women and infants. During this important investigation into the linkage between GDM patients and their altered expression in the serum, proteomics techniques were deployed to detect the differentially expressed proteins (DEPs) of in the serum of GDM patients to further explore its pathogenesis, and find out possible biomarkers to forecast GDM occurrence. AIM: To investigation serum proteins differentially expressed in GDM were assessed using isobaric tag for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analyses. METHODS: Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria. Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation, and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry. Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis, and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDM gravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest 16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteins associated with lipid metabolism, coagulation cascade activation, complement system and inflammatory response in the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serum of GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk of gestation. CONCLUSION: GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complement system and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.

Associations between benign paroxysmal positional vertigo and seven mental disorders: a two-sample Mendelian randomization study.

Background: The association between benign paroxysmal positional vertigo (BPPV) and various mental disorders is still controversial. This study used the Mendelian randomization (MR) method to clarify the correlation between BPPV and seven mental disorders (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings) to aid in the exploration of BPPV complications and prevention and early treatment of mental disorders. Methods: The datasets for BPPV and seven mental disorders were obtained from genome-wide association studies (GWASs). Two-sample MR was used to analyze the correlation between exposure (BPPV) and various outcomes (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings). A reverse MR study was also performed. The inverse variance weighting (IVW) method, the MR-Egger method, the simple mode method, the weighted mode method, and the weighted median method were selected. Results: The MR analysis and the reverse MR analysis results did not reveal significant associations between BPPV and bipolar disorder, depression, anxiety disorder, schizophrenia, suicidal tendencies, neuroticism, and mood swings. Interestingly, neuroticism (IVW: OR = 1.142, 95% CI: 1.059-1.231, P = 0.001; P-MR-PRESSO adjustment = 0.0002) and mood swings (IVW: OR = 3.119, 95% CI: 1.652-5.884, P = 0.0004) may have a significant association with BPPV. After MR-PRESSO adjustment, there was no horizontal pleiotropy or heterogeneity, and a significant association between neuroticism, mood swings, and BPPV has still been suggested. Conclusion: We conducted MR analysis on genetic data from European populations and discovered a causal relationship between BPPV and the seven mental disorders. Our research findings suggest that BPPV may not have a significant causal relationship with bipolar disorder, depression, anxiety disorder, schizophrenia, or suicidal tendencies. However, neuroticism and mood swings may be risk factors for BPPV.

A qualitative study of Chinese parental perspectives on the causes of Tourette syndrome in children.

Parents' beliefs and attitudes toward their children with Tourette syndrome (TS) influence treatment-seeking behaviors. This study aimed to explore and describe the Chinese parents' perspectives on the causes of TS for their children. A qualitative study using semi-structured interviews was conducted with the parents of TS patients from a children's hospital in western China from June to July 2021, and thematic analysis was performed to transcribe interviews and identify themes. A total of 13 participants were interviewed in this study. Five themes were developed in relation to the cognition of the causes of TS in parents, including physical problems, parenting and education problems, mental problems, bad habits, and neurological problems. Due to the insufficient awareness of TS, most parents repeatedly seek medical advice that they regarded the symptoms as physical problems or neurological problems. They generally felt guilty and blamed themselves for their parenting styles and education methods. And some parents attributed it to the poor psychological quality or the bad habits of children. Study findings showed a lack of scientific understanding of the causes of TS among parents further hindered the timely effective treatment for patients and affected the family relationships, which highlights the importance of public education and raising awareness of the disease.

Comparison of hysterectomy cases performed by transvaginal natural orifice transluminal endoscopic surgery: A paired sample cross-sectional study.

This study aimed to investigate the feasibility, indications, and benefits of transvaginal natural orifice transluminal endoscopic surgery (v-NOTES) hysterectomy for nonmalignant gynecological diseases. The clinical data, including the baseline information and surgical conditions of 81 patients who underwent v-NOTES hysterectomy for nonmalignant gynecological diseases in a tertiary university hospital from October 2018 to August 2022, were retrospectively analyzed and compared with the total laparoscopic hysterectomy group (200 cases) and the transumbilical laparoendoscopic Single Site Surgery group (150 cases). In comparison with the other 2 groups, the highest proportion of patients in the v-NOTES group had cervical intraepithelial neoplasia. Accordingly, mean preoperative uterine volume measured by sonography was significantly smaller in the v-notes group. In the v-NOTES group, the mean number of vaginal deliveries and age were significantly higher, while the mean number of previous abdominal surgeries was lower compared to the other 2 groups. The V-NOTES group had a shorter operation time, shorter postoperative urinary catheter insertion time, earlier intestinal recovery days, shorter hospital stay, and lower visual analogue scale scores after surgery, and the differences were statistically significant. When indicated appropriately, v-NOTES hysterectomy can be a feasible and advantageous surgical modality. In particular, in comparison to the laparoendoscopic Single Site Surgery and total laparoscopic hysterectomy groups, the v-NOTES group had advantages in postoperative recovery and had more aesthetic surgical results.

Membrane-associated RING-CH 7 inhibits stem-like capacities of bladder cancer cells by interacting with nucleotide-binding oligomerization domain containing 1.

BACKGROUND: Cancer stem-like capacities are major factors contributing to unfavorable prognosis. However, the associated molecular mechanisms underlying cancer stem-like cells (CSCs) maintain remain unclear. This study aimed to investigate the role of the ubiquitin E3 ligase membrane-associated RING-CH 7 (MARCH7) in bladder cancer cell CSCs. METHODS: Male BALB/c nude mice aged 4-5 weeks were utilized to generate bladder xenograft model. The expression levels of MARCHs were checked in online databases and our collected bladder tumors by quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). Next, we evaluated the stem-like capacities of bladder cancer cells with knockdown or overexpression of MARCH7 by assessing their spheroid-forming ability and spheroid size. Additionally, we conducted proliferation, colony formation, and transwell assays to validate the effects of MARCH7 on bladder cancer CSCs. The detailed molecular mechanism of MARCH7/NOD1 was validated by immunoprecipitation, dual luciferase, and in vitro ubiquitination assays. Co-immunoprecipitation experiments revealed that nucleotide-binding oligomerization domain-containing 1 (NOD1) is a substrate of MARCH7. RESULTS: We found that MARCH7 interacts with NOD1, leading to the ubiquitin-proteasome degradation of NOD1. Furthermore, our data suggest that NOD1 significantly enhances stem-like capacities such as proliferation and invasion abilities. The overexpressed MARCH7 counteracts the effects of NOD1 on bladder cancer CSCs in both in vivo and in vitro models. CONCLUSION: Our findings indicate that MARCH7 functions as a tumor suppressor and inhibits the stem-like capacities of bladder tumor cells by promoting the ubiquitin-proteasome degradation of NOD1. Targeting the MARCH7/NOD1 pathway could be a promising therapeutic strategy for bladder cancer patients.

Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil.

OBJECTIVE: This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. METHODS: Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. RESULTS: A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. CONCLUSION: There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank.

PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.