Metabolomics analysis reveals the effects of Salvia Miltiorrhiza Bunge extract on ameliorating acute myocardial ischemia in rats induced by isoproterenol.

Salvia miltiorrhiza Bunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1 % in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.

Genome-based surveillance reveals cross-transmission of MRSA ST59 between humans and retail livestock products in Hanzhong, China.

Methicillin-resistant Staphylococcus aureus (MRSA) has been recognized in hospitals, community and livestock animals and the epidemiology of MRSA is undergoing a major evolution among humans and animals in the last decade. This study investigated the prevalence of MRSA isolates from ground pork, retail whole chicken, and patient samples in Hanzhong, China. The further characterization was performed by antimicrobial susceptibility testing and in-depth genome-based analysis to identify the resistant determinants and their phylogenetic relationship. A total of 93 MRSA isolates were recovered from patients (n = 67) and retail livestock products (n = 26) in Hanzhong, China. 83.9% (78/93) MRSA isolates showed multiple drug resistant phenotype. Three dominant livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) sequence types were identified: ST59-t437 (n = 47), ST9-t899 (n = 10) and ST398 (n = 7). There was a wide variation among sequence types in the distribution of tetracycline-resistance, scn-negative livestock markers and virulence genes. A previous major human MRSA ST59 became the predominant interspecies MRSA sequence type among humans and retail livestock products. A few LA-MRSA isolates from patients and livestock products showed close genetic similarity. The spreading of MRSA ST59 among livestock products deserving special attention and active surveillance should be enacted for the further epidemic spread of MRSA ST59 in China. Data generated from this study will contribute to formulation of new strategies for combating spread of MRSA.

Efficacy and Safety of Orally and Intravenously Administration of Tranexamic Acid in Patients with Elderly Femoral Neck Fracture.

OBJECTIVE: For elderly femoral neck fracture patients, anemia is one of the most common complications, increasing the risk of postoperative adverse events. Tranexamic acid (TXA) has been widely applied to the perioperative blood management. However, the optimal route of TXA administration in elderly femoral neck fracture remains unclear. The aim of this study is to evaluate the efficacy and safety of oral and intravenous (IV) application of TXA in elderly patients with femoral neck fracture undergoing total hip arthroplasty (THA) and hemiarthroplasty (HA). METHODS: All elderly patients aged over 65 years old diagnosed with femoral neck fracture admitted to the trauma orthopedics from August 1, 2020 to February 28, 2022 were enrolled in this prospective cohort study. Participants were divided into three groups: oral group: TXA 2g orally 2 h before incision; IV group: intravenous infusion of TXA 1g 15 min before incision; and control group: usual hemostatic method. The primary outcomes were total blood loss, allogeneic transfusion rate, and postoperative thromboembolic events. SPSS 23.0 (IBM, Armonk, NY, USA) was used for statistical analysis, and p ≤ 0.05 was considered statistically significant. RESULTS: A total of 100 patients were enrolled, including 32 cases in the oral group, 34 cases in the IV group and 34 cases in the control group. Compared with the control group, the total perioperative blood loss in the oral and IV groups was significantly decreased (763.92 ± 358.64 mL vs 744.62 ± 306.88 mL vs 1250.60 ± 563.37 mL, p = 0.048). No significant difference was identified between the oral and IV groups (p = 0.970). The rate of allogeneic transfusion was lower in the oral and IV groups than in the control group, but the difference had no statistical significant (6 vs 5 vs 12, p = 0.108), However, subgroup analysis showed that the IV and oral groups in patients who underwent THA have significant lower transfusion rate compared with the control group (1 vs 3 vs 7, p = 0.02). During 6 months follow-up, no thromboembolic events were identified. Two patients (one from the oral group and one from the control group) died of respiratory failure. The cost of blood management from the oral group was significantly lower than IV (p < 0.001) and control groups (p = 0.009). CONCLUSION: Elderly patients with femoral neck fracture undergoing THA can benefit from both IV and oral administration of tranexamic acid. The results of these two administration routes are similar in safety and effectiveness. A similar tendency was observed in patients undergoing HA. Oral TXA is more cost-benefit compared with intravenous applications.

[Transformation of scientific research results into teaching resources to improve the teaching effect: taking the teaching of the chromatographic method in the pharmaceutical analysis course as an example].

The pharmaceutical analysis course is a three-dimensional knowledge network that connects several courses to form a new comprehensive knowledge node involving a large knowledge system and flexible knowledge structure. In this course, the subject of chromatography covers a wide range of topics. However, because accurate content is challenging to present, the teaching effect of this subject is poor. In this work, we sought to achieve the educational purpose of establishing morality and cultivating talent, as well as the goal of training highly skilled professionals, by taking the teaching of chromatography in the pharmaceutical analysis course as an example of transforming scientific research results into teaching resources. The resources obtained are integrated into the teaching process to provide innovative and scientific research ideas to students with the aim of not only helping them understand and master technical knowledge but also exercise their ability to raise and solve problems. Furthermore, we expound on how to introduce scientific development frontiers and formulate scientific problems through curriculum design. We also describe how our strategy can promote the teaching effect and achieve teaching objectives. Based on the characteristics of rapid knowledge update and equal emphasis on theory and practice in pharmaceutical analysis, the course is designed by introducing new advances in scientific development, formulating scientific problems, and adopting question- and problem-based learning methods for teaching. The teaching effect is then evaluated through diversified assessment, student feedback, and self-evaluation. The results show that the transformation of scientific research results into teaching resources plays a significant role in stimulating students' interest in learning, improving students' ability to solve problems, and achieving curriculum objectives, all of which greatly improve the teaching effect.

Correction: Knowledge and Practices Regarding Human Papillomavirus and Cervical Cancer Screening Among Women in Low-Income Areas of China: A Cross-Sectional Study.

[This corrects the article DOI: 10.7759/cureus.55930.].

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Functional and structural investigation of a broadly neutralizing SARS-CoV-2 antibody.

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.

Building Medication Profiles in the Elderly: a Qualitative Study Based on Medication Information Literacy in a Long-Term Care Facility.

Purpose: Long-term care facilities are increasingly challenged with meeting the diverse healthcare needs of the elderly population, particularly concerning medication management. Understanding medication information literacy and behavior among this demographic is imperative. Therefore, this qualitative study aims to explore medication information literacy and develop distinct medication profiles among elderly long-term care residents. Material and Methods: In this study, we conducted in-depth semi-structured interviews with 32 participants aged 65 or older residing in a long-term care facility. The interviews were designed to explore participants' understanding of medication information, medication management practices, and experiences with healthcare providers. Thematic analysis was employed to analyze the interview data, allowing for the identification of common patterns and themes related to medication-taking behavior among the elderly residents. Results: The thematic analysis revealed four distinct medication behavior profiles among the elderly long-term care residents: (1) Proactive Health Self-Managers, (2) Medication Information Adherents, (3) Experience-Based Medication Users, and (4) Nonadherent Medication Users. These findings provide valuable insights into the diverse approaches to medication management within long-term care facilities and underscore the importance of tailored interventions to support the specific needs of each profile. Conclusion: This study highlights the necessity for tailored medication education and support to optimize medication management for the elderly. With the aging population expansion, addressing the unique medication challenges within long-term care facilities becomes increasingly critical. This research contributes to ongoing endeavors to enhance healthcare services for the elderly, striving for safer and more effective medication-taking behavior.

Correction: Prevalence of High-Risk Human Papillomavirus Infection, Associated Risk Factors, and Relationship With Cervical Precancerous Lesions in Perimenopausal and Older Women in an Area With High Cervical Cancer Incidence in China.

[This corrects the article DOI: 10.7759/cureus.58081.].

Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang & tang.

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.

Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up.

BACKGROUND: Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. METHODS: We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. RESULTS: The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. CONCLUSION: Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Numerical Optimization Study of Combustion and Heat Transfer Characteristics in Municipal Solid Waste Incinerators.

The efficient and clean utilization of urban waste can substitute for partial fossil fuels and reduce total carbon emissions. Fuel combustion is divided into three stages. Before the fire, the fuel is put into the furnace to reach the preparation stage of the fire temperature, the combustion stage takes place after the ignition temperature is reached, and finally, the combustion is completed. This article employs numerical simulation methods to comprehensively study the effects of various factors on the combustion characteristics of waste in a mechanical grate incinerator, including the inclination angle of the front arch, fuel properties, height of the front and rear arches, air distribution methods, and speed of the grate chain rotation. The results indicate that when the rear arch angle is set at 25°, the airflow distribution within the furnace is uniform and the high-temperature flue gas exhibits an ideal "L" shaped flow, achieving favorable characteristics of airflow distribution inside the furnace. With this structure, the airflow from the rear arch can adequately penetrate deep into the front arch area, thereby forming an efficient T-shaped combustion flame.

Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it. AIM OF THE STUDY: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism. MATERIALS AND METHODS: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H2O2-induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay. RESULTS: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H2O2-induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H2O2-stimulated HUVECs model. CONCLUSION: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation.

Knowledge and Practices Regarding Human Papillomavirus and Cervical Cancer Screening Among Women in Low-Income Areas of China: A Cross-Sectional Study.

BACKGROUND: Persistent human papillomavirus (HPV) infection is the primary cause of cervical cancer. However, this can be prevented through vaccination and screening. This study aimed to clarify the relationship between behavior, knowledge, and attitude toward cervical cancer and regular screening and HPV infection among women in Lueyang County. METHODS: Women who underwent cervical cancer screening at the outpatient department of a maternal and child health center between September and December 2021 were invited to participate. In total, 2,303 women completed the questionnaire. Women who underwent regular or irregular screening were 1:1 matched for age. Differences in knowledge of HPV and attitudes toward HPV vaccination among different populations were assessed. Logistic regression analysis was performed to identify the factors influencing HPV infection. RESULTS:  In total, 417 pairs of women who underwent regular and irregular screening were successfully matched. Multivariate logistic regression results indicated that age is a risk factor for HPV infection (OR=1.056 95%CI: [1.031 1.082]), while regular screening acts as a protective factor against HPV infection (OR=0.174 95%CI: [0.117 0.259]). Additionally, regular screening was associated with a higher level of knowledge about HPV among women compared to those who did not undergo regular screening (p<0.001). CONCLUSIONS:  Women in Lueyang County have low levels of knowledge regarding HPV and cervical cancer. Regular screening is a protective factor against HPV infection. The regular screening group demonstrates a higher level of HPV knowledge compared with the irregular screening group. These findings highlight the importance of regular screening and the need to strengthen public health education.

Structure optimizing of flavonoids against both MRSA and VRE.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

Intestinal flora: New perspective of type 2 diabetes.

Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors. Current diabetes management primarily focuses on blood glucose control, yet it is inherently progressive, necessitating increased reliance on exogenous blood glucose control methods over time. Therefore, there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications. The human intestinal microbiota, often referred to as the "second genome", exhibits significant diversity and plays a pivotal role in insulin resistance, glucose and lipid metabolism, and inflammatory response. Notably, Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus (T2DM) and proposed a novel therapeutic approach targeting intestinal microbes. This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora, thereby offering fresh avenues for understanding its pathogenesis and clinical management. This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies. Additionally, it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.

Hyponatremia-associated hospital visits are not reduced by early electrolyte testing in older adults starting antidepressants.

BACKGROUND: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. METHODS: Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8-60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score-based overlap weights. RESULTS: Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17-44 days), and the median sodium concentration measured in the community (136, IQR 133-138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130-134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8-60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16-2.46). CONCLUSIONS: Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring.

Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-ß Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor ß (TGF-ß) inhibitory activity via inhibiting the TGF-ß-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-ß/Smad signaling pathway.

Prevalence of High-Risk Human Papillomavirus Infection, Associated Risk Factors, and Relationship With Cervical Precancerous Lesions in Perimenopausal and Older Women in an Area With High Cervical Cancer Incidence in China.

Purpose This study delves into the epidemiology of high-risk human papillomavirus (HR-HPV) infection and its link to precancerous lesions among perimenopausal (40-59 years) and elderly (60-65 years) women in a Chinese county with a notably high incidence of cervical cancer. By uniquely focusing on these age groups in underdeveloped regions, the research aims to offer novel strategies for the management and prevention of cervical cancer. It seeks to inform targeted interventions and public health policies that could significantly benefit women at heightened risk for HPV, addressing a critical gap in current prevention efforts in economically disadvantaged communities. Methods This observational study was conducted at the Maternal and Child Health and Family Planning Service Centre in Lueyang County, from September 2021 to January 2022. It assessed 2008 women aged 40-65 for HPV screening, with 342 undergoing further cytological examination. The study evaluated the prevalence of HPV infection across different age groups and risk categories. It utilized a questionnaire to collect participants' basic information, health behaviors, and other relevant data to analyze factors influencing HR-HPV infection. Statistical analyses comprised chi-square tests, trend analysis, logistic regression, and multiple imputation techniques to address missing data. Results The prevalence of HR-HPV infection among women aged 40-65 years in Lueyang County was 18.43%. Older women exhibited a higher incidence of HPV infection, abnormal ThinPrep Cytology Test (TCT) results (Shaanxi Fu'an Biotechnology Co. Ltd., Baoji City, China), and low/high-grade squamous intraepithelial lesions (LSIL/HSIL) (P<0.05). The most prevalent HR-HPV genotypes in the overall, perimenopausal, and elderly groups were HPV-52, -53, and -58; HPV-52, -53, and -16; and HPV-58, -52, and -53, respectively. The prevalent HR-HPV genotypes in the abnormal The Bethesda System (TBS) results were HPV-16, -52, -33, -58; -16, -52, -58; and-16, -33, and -52. HPV-16, -18, -33 prevalence increased with increasing lesion severity (P<0.05). In this study, factors affecting HR-HPV in the three age groups were found to be mainly related to sexual behavior and education level, including history of lower genital tract diseases, multiple pregnancies, contraceptive methods without tubal ligation, age at first marriage greater than 18 years, never washing the vulva after sex, abstinence from sex, education level of junior high school or above, and spouse's education level of high school or above. Conclusions These findings suggest that the elevated rate of abnormal TBS in the older age group may be attributed to the higher prevalence of persistent infection-prone HR-HPV genotypes (HPV-58, -52, and-53), multiple infections, and potent oncogenic HR-HPV genotypes (HPV-16 and -33). Additionally, the higher HR-HPV prevalence in older patients may be related to lower education attainment, reduced screening rate, and limited condom usage. Therefore, strategies targeting perimenopausal and older women should prioritize enhancing health awareness, increasing screening rates, and encouraging condom utilization.