ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.

ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

ObjectiveTo analyze the epidemiological and clinical characteristics of surveillance cases in a sentinel hospital for pertussis in Jiangxi Province in 2019, and to provide corresponding references for the prevention and control of pertussis. MethodsCase investigation of pertussis was conducted among sentinel hospital surveillance cases, collecting their basic information, epidemiological characteristics, clinical characteristics, and other information. ResultsA total of 125 pertussis surveillance cases were investigated in 2019, including 73 clinically diagnosed cases (58.40%) and 52 confirmed cases (41.60%). The age of onset was mainly concentrated in children under 5 years old (108 cases, 86.40%), with the largest number of cases in infants aged less than 1-year-old (48 cases, 38.40%). Most cases had a history of receiving pertussis vaccine before onset (110 cases, 88.00%), and the intervals between the onset date and the date of last dose of pertussis vaccine in the 1‒2 doses group were significantly shorter than that in the 3‒4 doses group (U=-5.990, P<0.001). Probable household transmission of pertussis was found in 3 cases. All cases had cough symptoms, mainly manifested as whooping cough (77 cases, 61.60%), in addition to other main clinical manifestations, such as fever (76 cases, 60.80%), vomiting (30 cases, 24.00%), conjunctival congestion (27 cases, 21.60%), and inspiratory whoop (16 cases, 12.80%). A total of 73 cases (58.40%) experienced complications, including 1 death case. All the cases had multiple medical visit experiences before this visit, with an interval of 2 (0,3) days between the onset date and the first visit date. The misdiagnosis rate at the first medical visit was 88.00% (110/125), and the misdiagnosis rate of the first visit in secondary and primary hospitals was significantly higher than that in tertiary hospitals, exhibiting a statistically significant difference (χ²=21.582, P<0.001). ConclusionThe clinical symptoms of pertussis cases are often atypical, and the first diagnosis is prone to misdiagnosis, so it’s necessary to further strengthen the early diagnosis capabilities for pertussis cases in healthcare institutions, especially in the primary healthcare institutions.

Environmental damage affects many aspects of healthcare, from extreme weather events to evolving population disease. Singapore's healthcare sector has the world's second highest healthcare emissions per capita, hampering the nation's pledge to reduce emissions by 2030 and achieve net zero emissions by 2050. In this review, we provide an overview of the impact environmental damage has on healthcare, including facilities, supply chain and human health, and examine measures to address healthcare's impact on the environment. Utilising the 'R's of sustainability - rethinking, reducing/refusing, reusing/repurposing/reprocessing, repairing, recycling and research - we have summarised the opportunities and challenges across medical disciplines. Awareness and advocacy to adopt strategies at institutional and individual levels is needed to revolutionise our environmental footprint and improve healthcare sustainability. By leveraging evidence from ongoing trials and integrating sustainable practices, our healthcare system can remain resilient against environment-driven challenges and evolving healthcare demands while minimising further impacts of environmental destruction.
Humans ; Climate Change ; Delivery of Health Care ; Singapore ; Conservation of Natural Resources ; Sustainable Development ; Environment

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

INTRODUCTION: Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up. METHOD: Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP. RESULTS: We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV. CONCLUSION We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans ; Post-Exposure Prophylaxis/methods* ; Female ; Child ; Adolescent ; Singapore/epidemiology* ; HIV Infections/prevention & control* ; Male ; Sexually Transmitted Diseases/epidemiology* ; Retrospective Studies ; Hepatitis B/prevention & control* ; Follow-Up Studies ; Child, Preschool ; Sex Offenses/statistics & numerical data* ; Child Abuse, Sexual