Mean age and body mass index at type 2 diabetes diagnosis: Pooled analysis of 56 health surveys across income groups and world regions.

BACKGROUND: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young-onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2 ) at T2DM diagnosis in 56 countries. METHODS: Descriptive cross-sectional analysis of WHO STEPS surveys. We analysed adults (25-69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five-year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. RESULTS: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25-29 years and 8.5% were 30-34 years old; in women, 8.6% and 12.5% were 25-29 years and 30-34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. CONCLUSIONS: A non-negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Long-term follow-up after the treatment of impacted canines in the maxilla causing severe root resorption of the lateral incisors: two case reports.

BACKGROUND: Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare. CASE PRESENTATION: This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments. CONCLUSIONS: Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved.

Special issue "The advance of solid tumor research in China": Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling.

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3ß/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment.

Automatic retinoblastoma screening and surveillance using deep learning.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. METHODS: This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital from March 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. RESULTS: A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95% CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. CONCLUSIONS: DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. CLINICAL TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT05308043).

Is being childless associated with a woman's risk of overweight and obesity? Results from a national longitudinal study.

AIM: To examine the association between motherhood status (mothers, voluntarily childless, involuntarily childless) and overweight and obesity over 22 years. METHODS: A total of 4092 women aged 18-23 years were followed from 1996 to 2018. Motherhood status was defined by women's reports on their fertility, attempts to conceive, use of in vitro fertilisation and fertility hormones, and number of biological children. Associations between motherhood status and overweight and obesity were examined using generalised estimating equations models, adjusting for socio-demographic characteristics, lifestyle factors, depressive symptoms, early life factors, and polycystic ovary syndrome (PCOS). RESULTS: At age 40-45 years, 12% of women were voluntarily childless and 5% were involuntarily childless. The prevalence of overweight and obesity increased with age and women who were voluntarily or involuntarily childless had higher prevalence of obesity than mothers in all surveys. After adjusting for covariates, compared with mothers, women who were voluntarily childless had higher odds of being overweight (odds ratio [OR], 95% confidence interval [CI]: 1.29, 1.09-1.52) and obese (OR, 95% CI: 1.65, 1.29-2.12). Involuntary childlessness was not associated with being overweight (OR, 95% CI: 1.05, 0.82-1.33), and its association with obesity was attenuated after adjusting for PCOS in the final model (OR, 95% CI: 1.40, 0.99-1.98). CONCLUSIONS: Around one in nine Australian women remained voluntarily childless by their late reproductive years. On average, they had higher odds of being overweight and obese than mothers, suggesting that overweight and obesity prevention programs should consider tailoring their advice by motherhood status.

The role of Chemerin in human diseases.

Chemerin is a protein encoded by the Rarres2 gene that acts through endocrine or paracrine regulation. Chemerin can bind to its receptor, regulate insulin sensitivity and adipocyte differentiation, and thus affect glucose and lipid metabolism. There is growing evidence that it also plays an important role in diseases such as inflammation and cancer. Chemerin has been shown to play a role in the pathogenesis of inflammatory and metabolic diseases caused by leukocyte chemoattractants in a variety of organs, but its biological function remains controversial. In conclusion, the exciting findings collected over the past few years clearly indicate that targeting Chemerin signaling as a biological target will be a major research goal in the future. This article reviews the pathophysiological roles of Chemerin in various systems and diseases,and expect to provide a rationale for its role as a clinical therapeutic target.

Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Whether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown. Survival and perioperative outcomes were compared between the two groups in this meta-analysis to clarify this argument. METHODS: We searched 7 databases for eligible studies comparing TT and TA procedures for Siewert type II EGJA. The final analyzed endpoints included intraoperative and hospitalization outcomes, recurrence, complication, and survival. RESULTS: Seventeen studies involving 10,756 patients met the inclusion criteria. The TA group had higher rates of overall survival (OS) (HR: 1.31 [1.20 ~ 1.44], p < 0.00001) and disease-free survival (DFS) (HR: 1.49 [1.24 ~ 1.79], p < 0.0001). The survival advantage of OSR and DFSR increased with time. Subgroup analysis of OS and DFS suggested that TA remained the preferred approach among all subgroups. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. The analysis of perioperative outcomes revealed that the TA procedure was longer, had more intraoperative blood loss, and prolonged hospital stay. Similar R0 resection rates, as well as total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates, were found between the two groups. The safety analysis showed that the TT procedure led to more total complications, anastomotic leakages, cases of pneumonia, and cases of pleural effusion. CONCLUSIONS: The TA procedure appeared to be a suitable choice for patients with Siewert type II EGJA because of its association with longer survival, fewer recurrences, and better safety.

Diffusion-Weighted MR Imaging of the Optic Nerve Can Improve the Detection of Post-Laminar Optic Nerve Invasion from Retinoblastoma.

BACKGROUND: Post-laminar optic nerve invasion (PLONI) is a high-risk factor for the metastasis of retinoblastoma (RB). Unlike conventional MRI, diffusion-weighted imaging (DWI) reflects histopathological features, and may aid the assessment of PLONI. PURPOSE: To determine the value of conventional MRI plus DWI in detecting PLONI in RB patients. STUDY TYPE: Retrospective. POPULATION: Eighty-three RB patients, including 28 with histopathologically proven PLONI and 55 without PLONI. FIELD STRENGTH/SEQUENCE: 3.0 T, precontrast axial T1-weighted and T2-weighted imaging, DWI, and postcontrast axial, coronal, and oblique-sagittal T1-weighted imaging. ASSESSMENT: PLONI was assessed using post-enucleation histology and preoperative MRI features (optic nerve signal intensity, enlargement, and enhancement on conventional MRI, and apparent diffusion coefficient [ADC] of the optic nerve on DWI) evaluated by three observers. STATISTICAL TESTS: MRI features suggesting the presence of PLONI were identified using univariable and multivariable analyses. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze diagnostic performance. RESULTS: Optic nerve enhancement and low ADC of the optic nerve were significant indicators of PLONI. ROC curve analysis showed that the AUC of the combination of these two features for detecting PLONI was 0.87 (95% confidence interval [CI]: 0.78-0.93). The diagnostic performance of this model was significantly superior to that of optic nerve enhancement alone (0.76, 95% CI: 0.65-0.85) and marginally superior to that of the ADC of the affected optic nerve (0.78, 95% CI: 0.68-0.87, P = 0.051). DATA CONCLUSION: Conventional MRI combined with DWI can improve the detection of PLONI in RB patients over conventional MRI alone. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases.

The inflammasome is a multimeric protein complex located in the cytoplasm that is activated by many factors and subsequently promotes the release of proinflammatory factors such as interleukin (IL)-1ß and IL-18, resulting in a series of inflammatory responses that ultimately lead to the occurrence of various diseases. The Nod-like receptor protein 3 (NLRP3) inflammasome is the most characteristic type and the most widely studied among many inflammasomes. Activation of the NLRP3 inflammasome is closely related to the occurrence of many diseases, such as Alzheimer's disease. At present, a large number of studies have focused on the mechanisms underlying the activation of the NLRP3 inflammasome. Plenty of articles have reported the activation of the NLRP3 inflammasome by various ions, such as K+ and Na+ reflux and Ca2+ influx. However, few articles have reviewed the effects of various ion channels on the activation of the NLRP3 inflammasome and the relationship between the diseases caused by these proteins. This article mainly summarizes the relationship between intracellular and extracellular ion activities and ion channels and the activation of the NLRP3 inflammasome. We also provide a general summary of the diseases of each system caused by NLRP3 activation. We hope that more research will provide options for the treatment of diseases driven by the NLRP3 inflammasome.

Preoperative prediction of macrotrabecular-massive hepatocellular carcinoma based on B-Mode US and CEUS.

OBJECTIVES: To develop a preoperative prediction model to identify macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) and evaluate the model's diagnostic performance in differentiating MTM-HCC from HCC. METHODS: We conducted a mono-center retrospective study in a grade A tertiary hospital in China. Consecutive patients with suspected HCC from February 2019 to December 2020 were eligible for inclusion. All consenting patients underwent CEUS examination and were histologically diagnosed. Based on the clinical and US features between the two groups, we developed a binary logistic regression model and a nomogram for predicting MTM-HCC. RESULTS: A total of 161 patients (median age, 57 years; interquartile range, 48-64 years; 129 men) were included in the analysis. Twenty-seven of the HCCs (16.8%) were of the MTM subtype. Binary logistic regression analysis indicated that PVP hypoenhancement (OR = 15.497; 95% CI: 1.369, 175.451; p = 0.027), AFP > 454.6 ng/mL (OR = 8.658; 95% CI: 3.030, 24.741; p < 0.001), ALB ≤ 29.9 g/L (OR = 3.937; 95% CI: 1.017, 15.234; p = 0.047), halo sign (OR = 3.868; 95% CI: 1.314, 11.391; p = 0.016), and intratumoral artery (OR = 2.928; 95% CI: 1.039, 8.255; p = 0.042) were predictors for MTM subtype. Combining any two criteria showed a high sensitivity (100.0%); combining all five criteria showed a high specificity (99.2%); and the AUC value of the logistic regression model was 0.88 (95% CI: 0.81, 0.92). CONCLUSIONS: BMUS and CEUS could be used for identifying patients suspected of having MTM-HCC. Combining clinical information, BMUS, and CEUS features could achieve a noninvasive diagnosis of MTM-HCC. KEY POINTS: • Contrast-enhanced ultrasound examination helps clinicians to identify MTM-HCCs preoperatively. • PVP hypoenhancement, high AFP levels, low ALB levels, halo signs, and intratumoral arteries could be used to predict MTM-HCCs. • A logistic regression model and nomogram were built to noninvasively diagnose MTM-HCCs with an AUC value of 0.88 (95% CI: 0.81, 0.92).

San Jie Tong Mai Fang Protects Against Atherosclerosis Progression by Regulating Macroautophagy through the PI3K/AKT/mTOR Signaling Pathway.

ABSTRACT: Many studies have confirmed that macrophage autophagy injury negatively impacts the pathogenesis of atherosclerosis (AS). Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE -/- high-fat diet-fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins-key autophagy molecules-were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE -/- mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS.

Comparison of day surgery between varicose veins with and without superficial venous thrombosis below knee: a propensity score-matched analysis.

OBJECTIVES: Development of endovenous treatment and sclerotherapy technology makes it feasible for clinicians to treat varicose veins (VV) through day surgery (DS). Superficial venous thrombosis (SVT) of lower extremities is a common complication of VV. This study aimed to investigate whether the existence of SVT below knee affect the safety and efficacy of DS for VV patients. METHODS: This is a single-center retrospective study. Clinical data of 593 VV patients was retrospectively analyzed. Raw data were matched by the using of propensity score matching model. Operation time, technical failure, postoperative DVT, skin burns, saphenous nerve injury, subcutaneous induration, and bleeding were compared between the groups. Also, we compared VV recurrence, SVT formation, DVT events and the change of VCSS score with 12 months. RESULTS: Fifty-nine patients complicated with SVT below knee were matched with 118 patients had VV only. Perioperative and follow-up outcomes were similar in both groups except for the number of incisions (median = 6 [5, 7] VS median = 4 [4, 5], P < 0.001). Both groups experienced a great decrease in VCSS score. CONCLUSION: We systematically compared the clinical outcomes of DS in VV patients. Our results indicate DS is safe and effective for patients with VV, whether accompanied by SVT below the knee. TRIAL REGISTRATION: The ClinicalTrials.gov identifier for this trial is NCT05380895 (retrospectively registered).

Beneficial effects of dietary capsaicin in gastrointestinal health and disease.

Chili pepper and its major active compound capsaicin have long been used not only a daily food additive but also medication worldwide. Like in other human organs and systems, capsaicin has multiple actions in gastrointestinal (GI) physiology and pathology. Numerous studies have revealed that capsaicin acts on GI tract in TRPV1-dependent and -independent manners, mostly depending on its consumption concentrations. In this review, we will focus on the beneficial role of capsaicin in GI tract, a less highlighted aspect, in particular how dietary capsaicin affects GI health, the mechanisms of actions and its preventive/therapeutic potentials to several GI diseases. Dietary capsaicin affects GI tract not only via TRPV1-derpendent and independent manners, but also via acute and chronic effects. Although high dose intake of dietary capsaicin is harmful to human health sometimes, current literatures suggest that appropriate dose intake is likely beneficial to GI health and is preventive/therapeutic to GI disease in most cases as well. With extensive and intensive studies on its GI actions, capsaicin, as a daily consumed food additive, has potential to become a safe drug for the treatment of several GI diseases.

Do mothers or females without children have better health-related quality of life across their reproductive years?

PURPOSE: To compare health-related quality of life (HRQoL) between mothers and females who were voluntarily or involuntarily childless, across their reproductive years. METHODS: 4100 females born in 1973-78 from the Australian Longitudinal Study on Women's Health were followed for 22 years. Motherhood status was defined by females' reports in Survey 8 (2018, 40-45 years) on their fertility, attempts to conceive, use of in vitro fertilization and fertility hormones, and number of children. HRQoL was assessed in each survey using the 36-Item Short Form Survey (SF-36). Linear mixed models were used to assess the associations between motherhood status and HRQoL. RESULTS: Over 22 years, compared with females who were voluntarily childless, mothers on average had better HRQoL (shown by scores 1.5 to 3.4 points higher on five of the eight SF-36 subscales), while females who were involuntarily childless scored 2.2 to 3.0 points lower on three of eight SF-36 subscales. Compared with females who were voluntarily childless, teen mothers (age at first birth < 20 years) scored lower on role limitations due to physical problems subscale (b = -5.5, 95% CI: -9.3, -1.6), while females with either two, or three or more children scored 1.6 to 4.8 points higher on seven of eight SF-36 subscales. CONCLUSIONS: Females who were childless had poorer HRQoL than mothers. Further research is needed to understand the underlying mechanisms, which could inform policymakers on how to reduce the health disparities and improve long-term health outcomes for females.

Prognostic Value of the Radiomics-Based Model in the Disease-Free Survival of Pretreatment Uveal Melanoma: An Initial Result.

OBJECTIVE: The aim of this study was to develop a pretreatment magnetic resonance imaging (MRI)-based radiomics model for disease-free survival (DFS) prediction in patients with uveal melanoma (UM). METHODS: We randomly assigned 85 patients with UM into 2 cohorts: training (n = 60) and validation (n = 25). The radiomics model was built from significant features that were selected from the training cohort by applying a least absolute shrinkage and selection operator to pretreatment MRI scans. Least absolute shrinkage and selection operator regression and the Cox proportional hazard model were used to construct a radiomics score (rad-score). Patients were divided into a low- or a high-risk group based on the median of the rad-score. The Kaplan-Meier analysis was used to evaluate the association between the rad-score and DFS. A nomogram incorporating the rad-score and MRI features was plotted to individually estimate DFS. The model's discrimination power was assessed using the concordance index. RESULTS: The radiomics model with 15 optimal radiomics features based on MRI performed well in stratifying patients into the high- or a low-risk group of DFS in both the training and validation cohorts (log-rank test, P = 0.009 and P = 0.02, respectively). Age, basal diameter, and height were selected as significant clinical and MRI features. The nomogram showed good predictive performance with concordance indices of 0.741 (95% confidence interval, 0.637-0.845) and 0.912 (95% confidence interval, 0.847-0.977) in the training and validation cohorts, respectively. Calibration curves demonstrated good agreement. CONCLUSION: The developed clinical-radiomics model may be a powerful predictor of the DFS of patients with UM, thereby providing evidence for preoperative risk stratification.

The association between depression during perimenopause and progression of chronic conditions and multimorbidity: results from a Chinese prospective cohort.

PURPOSE: The association between perimenopausal depression and many chronic conditions among women has been well-established. However, the role of depression during perimenopause in the progression of multiple chronic conditions (multimorbidity) remains poorly understood. MATERIAL AND METHODS: A total of 1,216 community-dwelling women in their perimenopause period between 2010 and 2016 were enrolled in our analysis, and followed up for the progression of multimorbidity. Depression, as well as its severity, was evaluated by the Center for Epidemiologic Studies Depression 10-item scale (CES-D-10). Progression of multimorbidity was defined as the first report of two or more chronic conditions for participants without multimorbidity or the new report of one or more conditions for those with multimorbidity. Univariable and multivariable Cox proportional hazards model and the restricted cubic spline regression model were performed to assess the prospective association between perimenopausal depression and the progression of multimorbidity. RESULTS: A total of 480 (39.5%) women reported depression during perimenopause, and 529 (43.5%) women progressed to multimorbidity. After adjusting for socio-demographic and lifestyle factors, perimenopausal depression was independently associated with the progression of multimorbidity (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.13 to 1.60). Moreover, the severity of depression was positively and linearly associated with the progression of multimorbidity (P < 0.05). CONCLUSIONS: Our finding reveals a prospective association between perimenopausal depression and the progression of multimorbidity, indicating interventions targeting perimenopausal depression may reduce the burden of chronic diseases and multimorbidity in women's post-menopausal life.

Association between multimorbidity and informal long-term care use in China: a nationwide cohort study.

BACKGROUND: The impact of multimorbidity on long-term care (LTC) use is understudied, despite its well-documented negative effects on functional disabilities. The current study aims to assess the association between multimorbidity and informal LTC use in China. We also explored the socioeconomic and regional disparities. METHODS: The study included 10,831 community-dwelling respondents aged 45 years and older from the China Health and Retirement Longitudinal Study in 2011, 2015, and 2018 for analysis. We used a two-part model with random effects to estimate the association between multimorbidity and informal LTC use. Heterogeneity of the association by socioeconomic position (education and income) and region was explored via a subgroup analysis. We further converted the change of informal LTC hours associated with multimorbidity into monetary value and calculated the 95% uncertainty interval (UI). RESULTS: The reported prevalence of multimorbidity was 60·0% (95% CI: 58·9%, 61·2%) in 2018. We found multimorbidity was associated with an increased likelihood of receiving informal LTC (OR = 2·13; 95% CI: 1·97, 2·30) and more hours of informal LTC received (IRR = 1·20; 95% CI: 1·06, 1·37), ceteris paribus. Participants in the highest income quintile received more hours of informal LTC care (IRR = 1·62; 95% CI: 1·31, 1·99). The estimated monetary value of increased informal LTC hours among participants with multimorbidity was equivalent to 3·7% (95% UI: 2·2%, 5·4%) of China's GDP in 2018. CONCLUSION: Our findings substantiate the threat of multimorbidity to LTC burden. It is imperative to strengthen LTC services provision, especially among older adults with multimorbidity and ensure equal access among those with lower income.

Protoporphyrin IX-loaded albumin nanoparticles reverse cancer chemoresistance by enhancing intracellular reactive oxygen species.

Chemoresistance is the main cause of chemotherapy failure in ovarian cancer (OC). The enhanced scavenging of reactive oxygen species (ROS) by the thioredoxin system resulted in insufficient intracellular concentrations of effective ROS, leading to chemoresistance. To induce OC cell apoptosis by enhancing intracellular ROS levels, protoporphyrin IX (PpIX) and albumin-bound PTX nanoparticles (APNP) were utilized to fabricate APNP-PpIX nanoparticles. APNP-PpIX effectively generated ROS and increased the effective ROS concentration in chemoresistant cancer cells. The in vitro and in vivo experiments confirmed the effective inhibition of APNP-PpIX on chemoresistant OC cell proliferation and tumor formation. APNP-PpIX significantly improved the effectiveness of chemotherapy and photodynamic therapy, thus providing a new approach for the clinical treatment of chemoresistant OC.

Multimorbidity burden and developmental trajectory in relation to later-life dementia: A prospective study.

INTRODUCTION: This study assessed the associations of multimorbidity burden and its developmental trajectory with later-life dementia. METHODS: Among 5923 Health and Retirement Study participants, major chronic conditions including hypertension, diabetes mellitus, cancer, lung diseases, heart disease, stroke, psychological disorders, and arthritis were self- or proxy-reported in 1994-2008. Dementia diagnosis was self- or proxy-reported in 2008-2018. We used Cox regression to assess the associations of multimorbidity with incident dementia. RESULTS: During follow-up (median = 8 years), 701 participants developed dementia. Each additional chronic condition in 2008 was related to 15% (confidence interval: 9% to 22%) higher hazard of dementia. Multimorbidity trajectories in 1994-2008 were classified as "rapid growth", "steady growth", "slow growth", and "no new condition" by the group-based trajectory modelling methods. Compared to "no new condition", the "rapid growth" trajectory was related to 32% (3% to 69%) higher dementia risk. CONCLUSIONS: Both multimorbidity burden and its developmental trajectory were prospectively associated with risk of dementia.