hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. METHODS: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. RESULTS: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. CONCLUSIONS: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP.

Peritoneal dialysis versus haemodialysis for people commencing dialysis.

BACKGROUND: Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials (RCTs) have evaluated PD versus HD. The benefits and harms of the two modalities remain uncertain. This review includes both RCTs and non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of PD, compared to HD, in people with kidney failure initiating dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies from 2000 to June 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. MEDLINE and EMBASE were searched for NRSIs from 2000 until 28 March 2023. SELECTION CRITERIA: RCTs and NRSIs evaluating PD compared to HD in people initiating dialysis were eligible. DATA COLLECTION AND ANALYSIS: Two investigators independently assessed if the studies were eligible and then extracted data. Risk of bias was assessed using standard Cochrane methods, and relevant outcomes were extracted for each report. The primary outcome was residual kidney function (RKF). Secondary outcomes included all-cause, cardiovascular and infection-related death, infection, cardiovascular disease, hospitalisation, technique survival, life participation and fatigue. MAIN RESULTS: A total of 153 reports of 84 studies (2 RCTs, 82 NRSIs) were included. Studies varied widely in design (small single-centre studies to international registry analyses) and in the included populations (broad inclusion criteria versus restricted to more specific participants). Additionally, treatment delivery (e.g. automated versus continuous ambulatory PD, HD with catheter versus arteriovenous fistula or graft, in-centre versus home HD) and duration of follow-up varied widely. The two included RCTs were deemed to be at high risk of bias in terms of blinding participants and personnel and blinding outcome assessment for outcomes pertaining to quality of life. However, most other criteria were assessed as low risk of bias for both studies. Although the risk of bias (Newcastle-Ottawa Scale) was generally low for most NRSIs, studies were at risk of selection bias and residual confounding due to the constraints of the observational study design. In children, there may be little or no difference between HD and PD on all-cause death (6 studies, 5752 participants: RR 0.81, 95% CI 0.62 to 1.07; I2 = 28%; low certainty) and cardiovascular death (3 studies, 7073 participants: RR 1.23, 95% CI 0.58 to 2.59; I2 = 29%; low certainty), and was unclear for infection-related death (4 studies, 7451 participants: RR 0.98, 95% CI 0.39 to 2.46; I2 = 56%; very low certainty). In adults, compared with HD, PD had an uncertain effect on RKF (mL/min/1.73 m2) at six months (2 studies, 146 participants: MD 0.90, 95% CI 0.23 to 3.60; I2 = 82%; very low certainty), 12 months (3 studies, 606 participants: MD 1.21, 95% CI -0.01 to 2.43; I2 = 81%; very low certainty) and 24 months (3 studies, 334 participants: MD 0.71, 95% CI -0.02 to 1.48; I2 = 72%; very low certainty). PD had uncertain effects on residual urine volume at 12 months (3 studies, 253 participants: MD 344.10 mL/day, 95% CI 168.70 to 519.49; I2 = 69%; very low certainty). PD may reduce the risk of RKF loss (3 studies, 2834 participants: RR 0.55, 95% CI 0.44 to 0.68; I2 = 17%; low certainty). Compared with HD, PD had uncertain effects on all-cause death (42 studies, 700,093 participants: RR 0.87, 95% CI 0.77 to 0.98; I2 = 99%; very low certainty). In an analysis restricted to RCTs, PD may reduce the risk of all-cause death (2 studies, 1120 participants: RR 0.53, 95% CI 0.32 to 0.86; I2 = 0%; moderate certainty). PD had uncertain effects on both cardiovascular (21 studies, 68,492 participants: RR 0.96, 95% CI 0.78 to 1.19; I2 = 92%) and infection-related death (17 studies, 116,333 participants: RR 0.90, 95% CI 0.57 to 1.42; I2 = 98%) (both very low certainty). Compared with HD, PD had uncertain effects on the number of patients experiencing bacteraemia/bloodstream infection (2 studies, 2582 participants: RR 0.34, 95% CI 0.10 to 1.18; I2 = 68%) and the number of patients experiencing infection episodes (3 studies, 277 participants: RR 1.23, 95% CI 0.93 to 1.62; I2 = 20%) (both very low certainty). PD may reduce the number of bacteraemia/bloodstream infection episodes (2 studies, 2637 participants: RR 0.44, 95% CI 0.27 to 0.71; I2 = 24%; low certainty). Compared with HD; It is uncertain whether PD reduces the risk of acute myocardial infarction (4 studies, 110,850 participants: RR 0.90, 95% CI 0.74 to 1.10; I2 = 55%), coronary artery disease (3 studies, 5826 participants: RR 0.95, 95% CI 0.46 to 1.97; I2 = 62%); ischaemic heart disease (2 studies, 58,374 participants: RR 0.86, 95% CI 0.57 to 1.28; I2 = 95%), congestive heart failure (3 studies, 49,511 participants: RR 1.10, 95% CI 0.54 to 2.21; I2 = 89%) and stroke (4 studies, 102,542 participants: RR 0.94, 95% CI 0.90 to 0.99; I2 = 0%) because of low to very low certainty evidence. Compared with HD, PD had uncertain effects on the number of patients experiencing hospitalisation (4 studies, 3282 participants: RR 0.90, 95% CI 0.62 to 1.30; I2 = 97%) and all-cause hospitalisation events (4 studies, 42,582 participants: RR 1.02, 95% CI 0.81 to 1.29; I2 = 91%) (very low certainty). None of the included studies reported specifically on life participation or fatigue. However, two studies evaluated employment. Compared with HD, PD had uncertain effects on employment at one year (2 studies, 593 participants: RR 0.83, 95% CI 0.20 to 3.43; I2 = 97%; very low certainty). AUTHORS' CONCLUSIONS: The comparative effectiveness of PD and HD on the preservation of RKF, all-cause and cause-specific death risk, the incidence of bacteraemia, other vascular complications (e.g. stroke, cardiovascular events) and patient-reported outcomes (e.g. life participation and fatigue) are uncertain, based on data obtained mostly from NRSIs, as only two RCTs were included.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Size-resolved environmentally persistent free radicals in urban road dust and association with transition metals.

Environmental persistent free radicals (EPFRs) are receiving growing concerns owing to their potentially adverse impacts on human health. Road dust is one important source of air pollution in most cities and may pose significant health risks. Characteristics of EPFRs in urban road dusts and its formation mechanism(s) are still rarely studied. Here, we evaluated occurrence and size distributions of EPFRs in road dusts from different functional areas of an urban city, and assessed relationship between EPFRs and some transition metals. Strong electron paramagnetic resonance signals of 6.01 × 1016 - 1.3 × 1019 spins/g with the mean g value of 2.0029 ± 0.0019 were observed, indicating that EPFRs consisted of a mixture of C-centered radicals, and C-centered radicals with an adjacent oxygen atom in the urban road dust. Much more EPFRs enriched in finer dust particles. EPFRs significantly correlated with the total Fe, but not water-soluble Fe, suggesting different impacts of water-soluble and insoluble metals in the formation of EFPRs. Health risk assessment results indicated high risk potentials via the ingestion and dermal exposure to EPFRs in road dusts. Future studies are calling to look into formation mechanisms of EPFRs in urban road dusts and to quantitatively evaluate its potential risks on human health.

[Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics].

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

Health care professionals and care staff challenges and experiences of managing sexual expression among older adults ≥60 years in long-term care facilities: a qualitative review and meta-synthesis.

Long-term care (LTC) facilities, in which older adults are institutionalised, have the responsibility to address their residents' rights, privacy and comfort in expressing themselves sexually in an acceptable manner. However, many older adults have reported barriers in their sexual expression, which is often a result of the care staff's attitudes in the facilities. This review synthesis evidence from qualitative studies on the challenges faced by care staff when supporting sexual expression of older residents in LTC facilities. The systematic review and meta-synthesis is reported according to the Enhanced Transparency in Reporting the Synthesis of Qualitative Research Statement. A systematic literature search for peer-reviewed studies was conducted on PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, PsycINFO, CINAHL and ProQuest Theses and Dissertations from inception until December 2020. Sandelowski and Barroso's two-step approach was used to synthesise the evidence. Seventeen qualitative studies published between 2004 and 2020 were included. This review encapsulated the experiences and challenges of 4,387 care staff whose age ranged from 18 to 69 years. Through the meta-synthesis, four themes were identified: varying manifestations of sexual expression and situations encountered, a spectrum of care staff's attitudes, setting boundaries in dementia care and workplace support. Managing sexual expression can be challenging for the care staff, given the complex interplay between personal beliefs, social contexts, moral dilemmas, practical barriers and the lack of clear policies. This review highlighted the need to equip them with knowledge, skills and confidence in managing sexuality in LTC facilities.

Nurses' perceptions of barriers and supportive behaviors in end-of-life care in the intensive care unit: a cross-sectional study.

BACKGROUND AND AIM: Patient deaths are common in the intensive care unit, and a nurse's perception of barriers to and supportive behaviors in end-of-life care varies widely depending upon their cultural background. The aim of this study was to describe the perceptions of intensive care nurses regarding barriers to and supportive behaviors in providing end-of-life care in a Chinese cultural context. METHODS: A cross-sectional survey was conducted among intensive care nurses in 20 intensive care units in 11 general hospitals in central and eastern China. Instruments used in this study were general survey and Beckstrand's questionnaire. Data were collected via online survey platform. Descriptive analysis was used to describe general characteristics of participants and mean and standard deviations of the barriers and supportive behaviors. The mean and standard deviation were used to describe the intensity and frequency of each barrier or supportive behavior following Beckstrand's method to calculate the score of barriers and supportive behaviors. Content analysis was used to analyze the responses to open-ended questions. RESULTS: The response rate was 53% (n = 368/700). Five of the top six barriers related to families and the other was the nurse's lack of time. Supportive behaviors included three related to families and three related to healthcare providers. Nurses in the intensive care unit felt that families should be present at the bedside of a dying patient, there is a need to provide a quiet, independent environment and psychological support should be provided to the patient and family. Nurses believe that if possible, families can be given flexibility to visit dying patients, such as increasing the number of visits, rather than limiting visiting hours altogether. Families need to be given enough time to perform the final rites on the dying patient. Moreover, it is remarkable that nurses' supportive behaviors almost all concern care after death. CONCLUSIONS: According to ICU-nurses family-related factors, such as accompany of the dying patients and acceptence of patient's imminent death, were found the major factors affecting the quality of end-of-life care. These findings identify the most prominent current barriers and supportive behaviors, which may provide a basis for addressing these issues in the future to improve the quality of end-of-life care.

Genes associated with inflammation may serve as biomarkers for the diagnosis of coronary artery disease and ischaemic stroke.

BACKGROUND: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms. METHODS: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients. RESULTS: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3. CONCLUSIONS: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

Inhibition of oxidative stress by testosterone improves synaptic plasticity in senescence accelerated mice.

It is well known that synaptic plasticity is associated with cognitive performance in Alzheimer's disease (AD). Testosterone (T) is known to exert protective effects on cognitive deficits in AD, but the underlying mechanisms of androgenic action on synaptic plasticity remain unclear. Thus, the aim of this study was to examine the protective mechanism attributed to T on synaptic plasticity in an AD senescence accelerated mouse prone 8 (SAMP8) model. The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region (2) phosphorylated N-methyl-D-aspartate receptor-1 (p-NMDAR1) and (3) phosphorylated calmodulin-dependent protein kinase II (p-CaMKII). In addition, the content of whole brain malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Treatment with T significantly elevated the number of intact pyramidal cells in hippocampal CA1 region and markedly increased hippocampal protein and mRNA expression levels of p-NMDAR1 and p-CaMK II. Further, T significantly decreased whole brain MDA levels accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of T on synaptic plasticity in a mouse AD model may be associated with reduction of oxidant stress.

Advances in antitumor polysaccharides from phellinus sensu lato: Production, isolation, structure, antitumor activity, and mechanisms.

Edible and medicinal fungi (mushrooms) are widely applied to functional foods and nutraceutical products because of their proven nutritive and medicinal properties. Phellinus sensu lato is a well-known medicinal mushroom that has long been used in preventing ailments, including gastroenteric dysfunction, diarrhea, hemorrhage, and cancers, in oriental countries, particularly in China, Japan, and Korea. Polysaccharides represent a major class of bioactive molecules in Phellinus s. l., which have notable antitumor, immunomodulatory, and medicinal properties. Polysaccharides that were isolated from fruiting bodies, cultured mycelia, and filtrates of Phellinus s. l. have not only activated different immune responses of the host organism but have also directly suppressed tumor growth and metastasis. Studies suggest that polysaccharides from Phellinus s. l. are promising alternative anticancer agents or synergizers for existing antitumor drugs. This review summarizes the recent development of polysaccharides from Phellinus s. l., including polysaccharide production, extraction and isolation methods, chemical structure, antitumor activities, and mechanisms of action.

Hand Rejuvenation by Targeted Volume Restoration of the Dorsal Fat Compartments.

BACKGROUND: Recent anatomic findings suggest aging-related changes of the complex fat distribution in the hand. OBJECTIVES: To rejuvenate the aging hand, we developed a targeted fat grafting technique based on the physiologic fat distribution of the hand. METHODS: The dorsum of both hands was examined in 30 healthy volunteers of different age utilizing B-mode ultrasound to determine physiological changes of the aging hand. Additional anatomic dissection was performed in 10 hands of five fresh cadavers to establish the anatomic basis for the targeted restoration technique. A total of 17 patients were treated for hand rejuvenation utilizing this technique and followed up for at least 6 months. The posttreatment outcome was assessed through B-mode ultrasound, 3-dimensional (3D) topography scanning, and a patient satisfaction survey. RESULTS: According to the fat distribution of the dorsum, hand aging was divided into three grades: (1) mild atrophy with rhytides; (2) moderate atrophy with exposed veins; and (3) serious atrophy with exposed tendons. Anatomic findings showed the existence of distinct superficial and deep fat compartments. The average fat grafting volume was 25.5 ml per hand dorsum administered in one or two procedures. Patients were monitored for 8.3 ± 2.6 months. After 6 months, a volume gain was found in all patients. The degree of aging was significantly reduced. The majority of patients (94.1%) were satisfied with their results. CONCLUSIONS: This study provides the anatomic and clinical basis for targeted restoration of the physiological fat volume in the hand dorsum with high satisfaction rates. LEVEL OF EVIDENCE: 4.

Heart rate variability predicts mortality in peritoneal dialysis patients.

BACKGROUND: The predictive value of heart rate variability (HRV) in peritoneal dialysis (PD) has never been tested. METHODS: In this study, the associations between HRV measures and the mortality in 81 PD patients were analyzed. HRV was measured by using 5-min recordings of a stationary system by a standardized method. Both time domain and frequency domain parameters were analyzed. RESULTS: During a follow-up period of 43.78 ± 14.77 months, 25 patients died, four patients were transferred to hemodialysis. Of the 81 patients, the time domain parameters, such as the standard deviation of differences between adjacent normal sinus to normal sinus (NN) intervals (SDSD) and the square root of the mean of the squared differences between adjacent normal NN intervals (RMSSD), were higher; the frequency domain parameters, such as the ratio of low-frequency power to high-frequency power (LF/HF) and the normalized LF, were lower, and the normalized HF was higher in the non-survived group as compared with the survived group. A Cox proportional hazards model analysis revealed that, of the HRV measures, decrease of the normalized LF, LF/HF and increase of rMSSD, SDSD, normalized HF had significant predictive value for mortality. After adjustment for other univariate predictors including age, urine volume, renal Kt/V, high-sensitivity C-reactive protein (hs-CRP), the predictive value of decreased LF/HF remained significant. Kaplan-Meier survival analysis showed mortality rate was much higher in patients with a low LF/HF (median value of 1.56). CONCLUSION: The decreases of LF/HF which reflects impaired sympathetic nerve regulation is an independent predictor of mortality in PD patients.

Adeno-associated virus 9 mediated FKRP gene therapy restores functional glycosylation of α-dystroglycan and improves muscle functions.

Mutations in the FKRP gene are associated with a wide range of muscular dystrophies from mild limb-girdle muscular dystrophy (LGMD) 2I to severe Walker-Warburg syndrome and muscle-eye-brain disease. The characteristic biochemical feature of these diseases is the hypoglycosylation of α-dystroglycan (α-DG). Currently there is no effective treatment available. In this study, we examined the adeno-associated virus serotype 9 vector (AAV9)-mediated gene therapy in the FKRP mutant mouse model with a proline to leucine missense mutation (P448L). Our results showed that intraperitoneal administration of AAV9-FKRP resulted in systemic FKRP expression in all striated muscles examined with the highest levels in cardiac muscle. Consistent with our previous observations, FKRP protein is localized in the Golgi apparatus in myofibers. Expression of FKRP consequently restored functional glycosylation of α-DG in the skeletal and cardiac muscles. Significant improvement in dystrophic pathology, serum creatine kinase levels and muscle function was observed. Only limited FKRP transgene expression was detected in kidney and liver with no detectable toxicity. Our results provided evidence for the utility of AAV-mediated gene replacement therapy for FKRP-related muscular dystrophies.

A novel strategy for calcium magnesium phosphate/carboxymethyl chitosan composite bone cements with enhanced physicochemical properties, excellent cytocompatibility and osteogenic differentiation.

Artificial bone substitutes for bone repair and reconstruction still face enormous challenges. Previous studies have shown that calcium magnesium phosphate cements (CMPCs) possess an excellent bioactive surface, but its clinical application is restricted due to short setting time. This study aimed to develop new CMPC/carboxymethyl chitosan (CMCS) composite bone cements consisting of mixed powders of active MgO, calcined MgO and calcium dihydrogen phosphate monohydrate. With this novel strategy, it can adjust the setting time and improve the compressive strength. The results confirmed that CMPC/CMCS composite bone cements were successfully developed with a controllable setting time (18-70 min) and high compressive strength (87 MPa). In addition, the composite bone cements could gradually degrade in PBS with weight loss up to 32% at 28 days. They also promoted the proliferation of pre-osteoblasts, and induced osteogenic differentiation. The findings indicate that CMPC/CMCS composite bone cements hold great promise as a new type of bone repair material in further and in-depth studies.

Instant and short-term effects of acupuncture for depression and anxiety in unstable angina pectoris patients with percutaneous coronary interventions.

Aim: Patients with unstable angina pectoris (UAP) usually present anxiety or depression during percutaneous coronary intervention (PCI). This study sought to investigate the instant and short-term effects of acupuncture for anxiety and depression in UAP patients with PCI. Methods: A total of 210 UAP patients who underwent PCI were recruited and randomly assigned (1:1:1) to acupuncture, placebo, or control groups. Enzyme-linked immunosorbent assay was used to detect the levels of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), advanced oxidation protein products (AoPPs), and oxidized low-density lipoprotein (OX-LDL). Serial questionnaires with the Hamilton Anxiety (HAMA) scale and the Pittsburgh Sleep Quality Index were evaluated, and heart rate variability indicators were obtained. Results: Primary end-point: low frequency/high frequency (HF) was lower in the electroacupuncture group (p = 0.014), while standard deviation of normal-to-normal intervals, average standard deviation of normal-to-normal intervals, percentage of successive intervals that differ more than 50 ms, and HF were increased with acupuncture (p = 0.018, p = 0.043, p = 0.016, and p = 0.002, respectively). Secondary end-point: significant improvements in anxiety levels (HAMA) were observed in the three groups (p < 0.001). The fasting insulin and HOMA-IR levels were similar between the control group and the acupuncture group (p = 0.285 and p = 0.165, respectively). The levels of IL-6 and AoPPs differed among the three groups (p = 0.021 and p < 0.001, respectively). However, no significant differences were found in fasting plasma glucose, fasting c-peptide, Hs-CRP, and OX-LDL levels among the three groups (p = 0.585, p = 0.611, p = 0.902, and p = 0.756, respectively). Conclusions: In this study, short-term acupuncture may potentially relieve clinical symptoms before PCI treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03789344).

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

The hippocampal salt-inducible kinase 2-CREB-regulated transcription co-activator 1 system mediates the antidepressant actions of paroxetine in mice.

The hippocampal salt-inducible kinase 2 (SIK2)-CREB-regulated transcription co-activator 1 (CRTC1) system has been demonstrated to participate in not only the pathogenesis of depression but also the antidepressant mechanisms of several antidepressant medications including fluoxetine, paroxetine, and mirtazapine. Like fluoxetine, paroxetine is also a widely used selective serotonin (5-HT) reuptake inhibitor (SSRI). Recent studies have indicated that paroxetine also modulates several pharmacological targets other than the 5-HT system. Here, we speculate that paroxetine regulates the hippocampal SIK2-CRTC1 system. Chronic stress models of depression, various behavioral tests, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription PCR, and genetic knockdown were used together in the present study. Our results show that the antidepressant actions of paroxetine in mice models of depression were accompanied by its preventing effects against chronic stress on hippocampal SIK2, CRTC1, and CRTC1-CREB binding. In contrast, genetic knockdown of hippocampal CRTC1 notably abrogated the antidepressant effects of paroxetine in mice. In summary, regulating hippocampal SIK2 and CRTC1 participates in the antidepressant mechanism of paroxetine, extending the knowledge of its pharmacological targets.

Oxidative Tandem Cyclization of Aromatic Acids with (Benzo)thiophenes: One-Pot Access to Planar Sulfur-Containing Polycyclic Heteroarenes for Lipid-Droplet-Targeted Probes.

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

Requests for health education from Chinese cancer patients during their recovery period: a cross-sectional study.

To determine the prevalence of posttreatment patient requests for health information from Chinese cancer patients during their recovery period, a cross-sectional, descriptive study using a mailed survey was conducted among 374 patients selected randomly. The survey addressed what types of information patients actually wanted but did not receive from their care providers. Questionnaires from 360 patients were received and analyzed. Approximately 76.0% of the patients did not receive health information and expressed the need for the information. The information about how to reduce emotional distress (90.1%), rehabilitation (76.2%), disease symptoms (59.3%), and nutritional support (56.8%) were paramount among patients' concerns. Only 12.8% hoped to acquire information on sexual health. Health information for cancer patients at the recovery stage in China is poor. A tripartite involvement of the hospital-family-community and the combined intervention related to physical sequelae and psychosocial factors are needed at the recovery stage.

[Evaluation of induction chemotherapy with vinorelbine plus cisplatin (NP) or docetaxel plus cisplatin (TP) combined with concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma].

OBJECTIVE: To compare the efficacy and side effects of induction chemotherapy with vinorelbine plus cisplatin (NP) or docetaxel plus cisplatin (TP) combined with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal carcinoma (NPC). METHODS: From January 2005 to December 2009, 146 patients with locally advanced nasopharyngeal carcinoma treated in our department were randomized into NP group (76 patients) or TP group (70 patients). Both groups received two cycles of induction chemotherapy and concurrent chemoradiotherapy. After three weeks of induction chemotherapy, the patients received concurrent chemoradiotherapy. The chemotherapy was recycled every three weeks. Two groups were treated with intensity-modulated radiation therapy. RESULTS: The short-term efficacy of NP group was similar to that of TP group. The 3-year overall survival rates, disease-free-survival rates, locoregional relapse-free survival rates and distant metastasis-free survival rates in the NP and TP groups were 84.2% and 82.9%, 71.1% and 74.3%, 89.5% and 91.4%, 81.6% and 77.1%, respectively (P > 0.05). The occurrence rates of leucopenia, anemia and acute mucositis were significantly higher in the TP group than those in the NP group (P < 0.05). The gastrointestinal toxicity, dermatitis and liver toxicity were similar in the two groups. CONCLUSIONS: The efficacy of NP regimen induction chemotherapy plus concurrent chemordiotherapy for advanced NPC is similar to that of TP regimen. The toxicity of the NP regimen is lower than that of NP regimen, tolerable, and with a good compliance.