The combination of berberine and isoliquiritigenin synergistically improved adipose inflammation and obesity-induced insulin resistance.

White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme-linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity-induced insulin resistance were verified using a diet-induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1-macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co-treatment with BBR and ISL upregulated the protein expression of the IRS1-PI3K-Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity-induced adipose inflammation and insulin resistance.

In Situ Construction of CuTCPP/Bi4O5Br2 Hybrids for Improved Photocatalytic CO2 and Cr(VI) Reduction.

Global warming and heavy metal pollution pose tremendous challenges to human development, and photocatalysis is considered to be an effective strategy to solve these problems. Herein, copper(II) tetra (4-carboxyphenyl) porphyrin (CuTCPP) molecules were successfully in situ loaded onto Bi4O5Br2 by a hydrothermal approach. A series of experimental results show that the light absorption capacity and photogenerated carrier separation efficiency were synchronously enhanced after the construction of CuTCPP/Bi4O5Br2 composites. Hence, the as-prepared composites possess significantly improved photocatalytic ability for both CO2 and Cr(VI) reduction. Specifically, CuTCPP/Bi4O5Br2-2 achieves a CO generation rate of 17.14 µmol g-1 under 5 h irradiation, which is twice as high as that of Bi4O5Br2 (8.57 µmol g-1). Besides, the optimized CuTCPP/Bi4O5Br2-2 also exhibits a removal rate of 61.87% for Cr(VI) within 100 min under irradiation. Furthermore, the mechanism of CO2 and Cr(VI) photoreduction was explored by in situ Fourier transform infrared spectroscopy and capture experiments, respectively. This work can be a reference toward the construction of photocatalysts with high activity for solar energy conversion.

Platelet-derived microparticles and their cargos: The past, present and future.

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

Identification of hub genes within the CCL18 signaling pathway in hepatocellular carcinoma through bioinformatics analysis.

Introduction: Hepatocellular carcinoma (HCC) is an aggressive malignancy, and CCL18, a marker of M2 macrophage activation, is often associated with tumor immune suppression. However, the role of CCL18 and its signaling pathway in HCC is still limited. Our study focuses on investigating the prognostic impact of CCL18 and its signaling pathway in HCC patients and biological functions in vitro. Methods: HCC-related RNA-seq data were obtained from TCGA, ICGC, and GEO. The 6 hub genes with the highest correlation to prognosis were identified using univariate Cox and LASSO regression analysis. Multivariate Cox regression analysis was performed to assess their independent prognostic potential and a nomogram was constructed. In vitro experiments, including CCK8, EdU, RT-qPCR, western blot, and transwell assays, were conducted to investigate the biological effects of exogenous CCL18 and 6 hub genes. A core network of highly expressed proteins in the high-risk group of tumors was constructed. Immune cell infiltration was evaluated using the ESTIMATE and CIBERSORT packages. Finally, potential treatments were explored using the OncoPredict package and CAMP database. Results: We identified 6 survival-related genes (BMI1, CCR3, CDC25C, CFL1, LDHA, RAC1) within the CCL18 signaling pathway in HCC patients. A nomogram was constructed using the TCGA_LIHC cohort to predict patient survival probability. Exogenous CCL18, as well as overexpression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1, can promote proliferation, migration, invasion, stemness, and increased expression of PD-L1 protein in LM3 and MHCC-97H cell lines. In the high-risk group of patients from the TCGA_LIHC cohort, immune suppression was observed, with a strong correlation to 21 immune-related genes and suppressive immune cells. Conclusion: Exogenous CCL18 promotes LM3 and MHCC-97H cells proliferation, migration, invasion, stemness, and immune evasion. The high expression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1 can serve as a biomarkers for immune evasion in HCC.

Pseudohalogen Ammonium Salt-Assisted Syntheses of Large-Sized Indium Phosphide Quantum Dots with Near-Infrared Photoluminescence.

The development of indium phosphide (InP)-based quantum dots (QDs) with a near-infrared (NIR) emission area still lags behind the visible wavelength region and remains problematic. This study describes a one-step in situ pseudohalogen ammonium salt-assisted approach to generate NIR-emitted InP-based QDs with high photoluminescence quantum yields (PLQYs). The coexistence of NH4+ and PF6- ions from NH4PF6 may in situ synchronously etch and passivate the surface oxides and impede the creation of traps under the whole growth process of InP QDs. Experimental findings demonstrated that the in situ pseudohalogen ammonium salt-assisted syntheses technique may feature emission at a full width at half-maximum (fwhm) peak as fine as ∼45 nm and broaden the emission range to around ∼780 nm. A two-step approach for ZnS shells was developed to further improve the PLQY of NIR-emitted InP QDs. Furthermore, the constructed high-power intrinsically stretchable NIR color-conversion film employing the InP-based QDs/polymer composites presented excellent luminescence conversion ability and stretchability.

Surface Passivation toward Multiple Inherent Dangling Bonds in Indium Phosphide Quantum Dots.

Indium phosphide (InP) quantum dots (QDs) have become the most recognized prospect to be less-toxic surrogates for Cd-based optoelectronic systems. Due to the particularly dangling bonds (DBs) and the undesirable oxides, the photoluminescence performance and stability of InP QDs remain to be improved. Previous investigations largely focus on eliminating P-DBs and resultant surface oxidation states; however, little attention has been paid to the adverse effects of the surface In-DBs on InP QDs. This work demonstrates a facile one-step surface peeling and passivation treatment method for both In- and P-DBs for InP QDs. Meanwhile, the surface treatment may also effectively support the encapsulation of the ZnSe shell. Finally, the generated InP/ZnSe QDs display a narrower full width at half-maximum (fwhm) of ∼48 nm, higher photoluminescence quantum yields (PLQYs) of ∼70%, and superior stability. This work enlarges the surface chemistry engineering consideration of InP QDs and considerably promotes the development of efficient and stable optoelectronic devices.

Palmatine alleviates cardiac fibrosis by inhibiting fibroblast activation through the STAT3 pathway.

Cardiac fibrosis, the hallmark of cardiovascular disease, is characterized by excessive deposition of extracellular matrix in the heart. Emerging evidence indicates that cardiac fibroblasts (CFs) play pivotal roles in driving cardiac fibrosis. However, due to incomplete insights into CFs, there are limited effective approaches to prevent or reverse cardiac fibrosis currently. Palmatine, a protoberberine alkaloid extracted from traditional Chinese botanical remedies, possesses diverse biological effects. This study investigated the potential therapeutic value and mechanism of palmatine against cardiac fibrosis. Adult male C57BL/6 mice were treated with vehicle, isoproterenol (ISO), or ISO plus palmatine for one week. After echocardiography assessment, mice hearts were collected for histopathology, real-time polymerase chain reaction, and Western blot analyses. Primary rat CFs were utilized in vitro. Compared to control, ISO-treated mice exhibited cardiac hypertrophy and structural abnormalities; however, treatment with palmatine ameliorated these effects of ISO. Moreover, palmatine treatment mitigated ISO-induced cardiac fibrosis. Network pharmacology and molecular docking analysis showed that palmatine strongly binds the regulators of cardiac fibrosis including signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin. Furthermore, palmatine reduced the elevated fibrotic factor expressions and overactivated STAT3 induced by ISO, Transformed growth factor ß1 (TGF-ß1), or interleukin-6 both in vivo and in vitro. Additionally, blocking STAT3 suppressed the TGF-ß1-induced CF activation. Collectively, these data demonstrated that palmatine attenuated cardiac fibrosis partly by inhibiting fibroblast activation through the STAT3 pathway. This provides an experimental basis for the clinical treatment of cardiac fibrosis with palmatine.

Modified Internal Pudendal Artery Perforator Flap Interposition for Rectovaginal Fistula.

IMPORTANCE: Rectovaginal fistula (RVF) is a challenging condition associated with recurrences and significant functional impairment. OBJECTIVES: The internal pudendal artery perforator (IPAP) flap has become a viable option for reconstructing the vagina and perineal regions. This study aims to introduce a modified technique of IPAP flap interposition and evaluate its postoperative outcomes in the treatment of low RVF. STUDY DESIGN: Sixteen patients with RVF who underwent modified IPAP flap interposition between 2016 and 2021 were retrospectively enrolled. Recurrence rate, the satisfaction of vulvar appearance (Visual Analog Scale), and quality of sexual life (Female Sexual Function Index score) were followed up and analyzed. RESULTS: All patients presented with low fistula with a mean diameter of 8.3 mm. The mean width and length of the IPAP flaps were 3.8 and 6.2 cm, respectively. The mean follow-up period was 14.1 months. All patients achieved successful healing without recurrence. High satisfaction was reported for the cosmetic effect of the vulva with a mean Visual Analog Scale score of 8.4. The proportion of female sexual disorder exhibited a statistically significant reduction, decreasing from 100% preoperatively to 38% after surgery (P < 0.05). CONCLUSIONS: The modified IPAP flap interposition is a reliable and safe option for repairing low RVF, with high success rates and minimal donor site morbidity. Moreover, this procedure provides a suitable volume flap and preserves the vaginal physiological environment, which benefits postoperative sexual function.

Nitrogen-Rich Conjugated Microporous Polymers with Improved Cobalt(II) Density for Highly Efficient Electrocatalytic Oxygen Evolution.

Developing efficient oxygen evolution catalysts (OECs) made from earth-abundant elements is extremely important since the oxygen evolution reaction (OER) with sluggish kinetics hinders the development of many energy-related electrochemical devices. Herein, an efficient strategy is developed to prepare conjugated microporous polymers (CMPs) with abundant and uniform coordination sites by coupling the N-rich organic monomer 2,4,6-tris(5-bromopyrimidin-2-yl)-1,3,5-triazine (TBPT) with Co(II) porphyrin. The resulting CMP-Py(Co) is further metallized with Co2+ ions to obtain CMP-Py(Co)@Co. Structural characterization results reveal that CMP-Py(Co)@Co has higher Co2+ content (12.20 wt %) and affinity toward water compared with CMP-Py(Co). Moreover, CMP-Py(Co)@Co exhibits an excellent OER activity with a low overpotential of 285 mV vs RHE at 10 mA cm-2 and a Tafel slope of 80.1 mV dec-1, which are significantly lower than those of CMP-Py(Co) (335 mV vs RHE and 96.8 mV dec-1). More interestingly, CMP-Py(Co)@Co outperforms most reported porous organic polymer-based OECs and the benchmark RuO2 catalyst (320 mV vs RHE and 87.6 mV dec-1). Additionally, Co2+-free CMP-Py(2H) has negligible OER activity. Thereby, the enhanced OER activity of CMP-Py(Co)@Co is attributed to the incorporation of Co2+ ions leading to rich active sites and enlarged electrochemical surface areas. Density functional theory (DFT) calculations reveal that Co2+-TBPT sites have higher activity than Co2+-porphyrin sites for the OER. These results indicate that the introduction of rich active metal sites in stable and conductive CMPs could provide novel guidance for designing efficient OECs.

Strain-Induced Surface Interface Dual Polarization Constructs PML-Cu/Bi12O17Br2 High-Density Active Sites for CO2 Photoreduction.

The insufficient active sites and slow interfacial charge transfer of photocatalysts restrict the efficiency of CO2 photoreduction. The synchronized modulation of the above key issues is demanding and challenging. Herein, strain-induced strategy is developed to construct the Bi-O-bonded interface in Cu porphyrin-based monoatomic layer (PML-Cu) and Bi12O17Br2 (BOB), which triggers the surface interface dual polarization of PML-Cu/BOB (PBOB). In this multi-step polarization, the built-in electric field formed between the interfaces induces the electron transfer from conduction band (CB) of BOB to CB of PML-Cu and suppresses its reverse migration. Moreover, the surface polarization of PML-Cu further promotes the electron converge in Cu atoms. The introduction of PML-Cu endows a high density of dispersed Cu active sites on the surface of PBOB, significantly promoting the adsorption and activation of CO2 and CO desorption. The conversion rate of CO2 photoreduction to CO for PBOB can reach 584.3 µmol g-1, which is 7.83 times higher than BOB and 20.01 times than PML-Cu. This work offers valuable insights into multi-step polarization regulation and active site design for catalysts.

Sodium hyaluronate hydrogel for wound healing and human health monitoring based on deep eutectic solvent.

Hydrogel dressings traditionally promote wound healing by maintaining moisture and preventing infection rather than by actively stimulating the skin to regulate cell behavior. Electrical stimulation (ES) is known to modulate skin cell behavior and to promote wound healing. This study describes the first multifunctional conductive hydrogel for wound healing and health monitoring based on a deep eutectic solvent (DES). Sodium hyaluronate and polydopamine constituted the hydrogel skeleton, and tea tree oil and Panax notoginseng extract were used as the active ingredients to induce adhesion, promote antioxidant and antibacterial activity, and support biocompatibility of the hydrogel. The inclusion of DES increases the temperature resistance of the hydrogel and improves its environmental adaptability. We used a small, portable coin battery-powered to provide electrical stimulation. Treatment with both the hydrogel and ES resulted in a stronger therapeutic effect than that provided by the commercial DuoDERM dressing. The hydrogel detected movement and strain when applied as a sensor. Overall, this study reports the development of a multifunctional conductive hydrogel dressing based on DES as a wound healing and health monitor.

Different survival strategies of the phosphate-mineralizing bacterium Enterobacter sp. PMB-5 in response to cadmium stress: Biomineralization, biosorption, and bioaccumulation.

The phosphate-mineralizing bacteria (PMBs) has shown great potential as a sustainable solution to support pollution remediation through its induced mineralization capacity. However, few studies have been conducted on the mechanism of cadmium (Cd) tolerance in PMBs. In this study, a PMB strain, Enterobacter sp. PMB-5, screened from Cd-contaminated rhizosphere soil, has high resistance to Cd (540 - 1220 mg/L) and solubilized phosphate (232.08 mg/L). The removal experiments showed that the strain PMB-5 removed 71.69-98.24% and 34.83-76.36% of Cd with and without biomineralization, respectively. The characterization result of SEM, EDS, TEM, XPS and XRD revealed that PMB-5 induced Cd to form amorphous phosphate precipitation through biomineralization and adopted different survival strategies, including biomineralization, bioaccumulation, and biosorption to resistance Cd in the microbial induced phosphate precipitation (MIPP) system and the non-MIPP system, respectively. Moreover, the results of whole genome sequencing and qRT-PCR indicated that phosphorus metabolism genes such as pst, pit, phn, ugp, ppk, etc. and heavy metal tolerance genes (including ion transport, ion efflux, redox, antioxidant stress), such as czcD, zntA, mgtA, mgtC, katE, SOD2, dsbA, cysM, etc. were molecular for the PMB-5 mineralization and Cd tolerance of PMB-5. Together, our findings suggested Enterobacter sp. PMB-5 is a potential target for developing more effective bioinoculants for Cd contamination remediation.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

Andrographolide attenuated MCT-induced HSOS via regulating NRF2-initiated mitochondrial biogenesis and antioxidant response.

Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1.

Associations of lipid accumulation product, visceral adiposity index, and triglyceride-glucose index with subclinical organ damage in healthy Chinese adults.

Background and aims: Obesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage. Methods: A total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage. Results: LAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI. Conclusion: LAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.

Clinical Effects of Surgical Left Atrial Reduction and Concomitant Mitral Valve Replacement in Patients with Giant Left Atrium.

INTRODUCTION: A giant left atrium may cause respiratory dysfunction and hemodynamic disturbance postoperatively. This retrospective study aimed to evaluate clinical effects of surgical left atrial reduction in concomitant cardiac valves operations. METHODS: One hundred and thirty-five patients with heart valve diseases and giant left atriums from January 2004 to July 2021 were enrolled into this research. They were divided into the folded group (n=63) and the unfolded group (n=72). Patients in the folded group had undergone cardiac valve operations concomitantly with left atrial reductions. The perioperative characteristics were compared between both groups, and subgroup analysis was performed. RESULTS: There were five deaths in the folded group and 25 deaths in the unfolded group (P<0.001). Complications including pneumonia, sepsis, multiple organs dysfunction syndrome, low cardiac output syndrome, and the use of continuous renal replacement therapy were significantly fewer in the folded group. The receiver operating characteristic curve of left atrial max. diameter predicting mortality was significant (area under the curve=0.878, P=0.005), and the cutoff point was 96.5 mm. The stratified analysis for sex showed that more female patients died in the unfolded group. Logistic regression for mortality showed that the left atrium unfolded, left atrial max. diameter, cardiopulmonary bypass time, and mechanical ventilation time increased the risk of death. CONCLUSION: Surgical left atrial reduction concomitantly with valves replacement could decrease mortality and was safe and effective in giant left atrium patients.

Global cardiovascular diseases burden attributable to high sodium intake from 1990 to 2019.

Sodium intake shows a positive correlation with blood pressure, resulting in an increased risk for cardiovascular diseases (CVD). Salt reduction is a key step toward the WHO's goal of 25% reduction in mortality from non-communicable diseases (NCDs) by 2025. This study aims to assess the current condition and temporal changes of the global CVD burden due to high sodium intake (HSI). We extracted data from the Global Burden of Disease (GBD) study 2019. The numbers and age-standardized rates of mortality and disability-adjusted life-years (DALYs), stratified by location, sex, and socio-demographic Index (SDI), were used to assess the high sodium intake attributable CVD burden from 1990 to 2019. The relationship between the DALYs rates and related factors was evaluated by stepwise multiple linear regression analysis. Globally, in 2019, the deaths and DALYs of HSI-related CVD were 1.72 million and 40.54 million, respectively, increasing by 41.08% and 33.06% from 1990. Meanwhile, the corresponding mortality and DALYs rates dropped by 35.1% and 35.2%, respectively. The high-middle and middle SDI quintiles bore almost two-thirds of CVD burden caused by HSI. And the leading cause of HSI attributable CVD burden was ischemic heart disease. Universal health coverage (UHC) was associated with the DALYs rates after adjustment. From 1990 to 2019, the global CVD burden attributable to HSI has declined with spatiotemporal and sexual heterogeneity. However, it remains a major public health challenge because of the increasing absolute numbers. Improving UHC serves as an effective strategy to reduce the HSI-related CVD burden.

Transvaginal Posterior Levatorplasty Combined with Perineoplasty: An Effective Surgical Method for Vaginal Rejuvenation.

BACKGROUND: Recently, gynecological cosmetic surgery and rejuvenation surgery have become increasingly popular, with a surging vaginal surgery demand for female vaginal laxity. However, follow-up data on the effectiveness of such procedures remain limited. OBJECTIVE: We conducted a retrospective study aimed to investigate the effects of transvaginal posterior levatorplasty combined with perineoplasty on vaginal rejuvenation. METHODS: Forty-five patients, who underwent transvaginal posterior levatorplasty combined with perineoplasty between July 2020 and May 2022, were included. Patient characteristics before operation, at baseline, 3, 6, and 12 months postoperatively, questionnaires on patient symptoms, quality of life, and sexual function, including Vaginal Laxity Questionnaire (VLQ) and Female Sexual Function Index (FSFI) were evaluated. Pelvic ultrasound imaging was performed preoperatively and 3 months postoperatively. RESULTS: Mean vaginal capacity index and Vaginal laxity scores were different at baseline, 6, and 12 months postoperatively (p<0.01). Female sexual function including libido, sexual arousal, lubrication, orgasm, sexual satisfaction and pain were significantly improved (preoperative: 21.68±4.15; 6 months postoperatively: 26.88±2.44; 1 year postoperatively: 29.97±2.10; p<0.01). The symptoms of stress urinary incontinence (SUI) and recurrent vaginitis were improved in 78.6% and 90.5% of the patients, respectively. In pelvic floor ultrasound, retrovesical angle (RVA), urethral rotation angle (URA), levator hiatus (LH), and bladder neck distance (BND) were significantly different preoperatively and at 3 months postoperatively (p<0.01). Overall satisfaction was 93.3% at 12 months postoperatively. CONCLUSIONS: Transvaginal posterior levatorplasty combined with perineoplasty is effective for the improvement of patient symptoms, quality of life, sexual function, SUI, and postnatal constipation. Further research on the underlying mechanism is required. LEVEL OF EVIDENCE: Therapeutic, III.

Spatial transcriptomics analysis of esophageal squamous precancerous lesions and their progression to esophageal cancer.

Esophageal squamous precancerous lesions (ESPL) are the precursors of esophageal squamous cell carcinoma (ESCC) including low-grade and high-grade intraepithelial neoplasia. Due to the absence of molecular indicators, which ESPL will eventually develop into ESCC and thus should be treated is not well defined. Indicators, for predicting risks of ESCC at ESPL stages, are an urgent need. We perform spatial whole-transcriptome atlas analysis, which can eliminate other tissue interference by sequencing the specific ESPL regions. In this study, the expression of TAGLN2 significantly increases, while CRNN expression level decreases along the progression of ESCC. Additionally, TAGLN2 protein level significantly increases in paired after-progression tissues compared with before-progression samples, while CRNN expression decreases. Functional studies suggest that TAGLN2 promotes ESCC progression, while CRNN inhibits it by regulating cell proliferation. Taken together, TAGLN2 and CRNN are suggested as candidate indicators for the risk of ESCC at ESPL stages.