The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

Objective To investigate the fatigue and workload status among medical students,and to explore the latent profiles of fatigue and workload and their effects on sleep and emotion.Methods A cross-sectional study design with convenience sampling was employed to distribute a comprehensive survey via mixed online and offline modes,and medical college students were enrolled as the subjects for this investigation.The general demographic data,depression,anxiety and stress scale,Pittsburgh sleep quality index,Epworth sleepiness scale,insomnia severity index,National Aeronautics and Space Administration task load index(NASA-TLX)and fatigue scale-14(FS-14)were used to investigate the basic information of the medical students,their emotions(depression,anxiety and stress),sleep(sleep quality,sleepiness and insomnia),workload and fatigue status.Based on latent profile analysis,the types of workload-fatigue profiles and differences in sleep and emotion were analyzed.Results A total of 485 medical students were enrolled,with an average age of(22.07±2.42)years.The total score of the NASA-TLX was 64.44±12.50,and the total score of the FS-14 was 7.90±3.63.Latent profile analysis identified 3 distinct workload-fatigue profiles:low workload-medium fatigue group(12.8％),medium workload-low fatigue group(32.8％),and high workload-high fatigue group(54.4％).Among these,the medium workload-low fatigue group exhibited the highest performance level(all P＜0.05),while the low workload-medium fatigue group showed the lowest effort level and performance level(all P＜0.05).The high workload-high fatigue group showed the highest task-related demand and frustration level(all P＜0.05).Regarding sleep and emotional status,the medium workload-low fatigue group had significantly better outcomes compared to the high workload-high fatigue group and the low workload-medium fatigue group(all P＜0.05).Conclusion Medical students experience a heavy workload and subjective fatigue.It is essential to appropriately adjust their workload,prioritize sleep and emotional well-being,and alleviate fatigue levels,so as to sustain personal physical and mental health.

Objective　To study the clinical and epidemiological characteristics of the monkeypox epidemic in Longgang District, Shenzhen, and conduct a comprehensive analysis and discussion to provide a reference for monkeypox epidemic prevention and control. Methods An epidemiological investigation was conducted on 16 monkeypox cases found in the medical institutions of Longgang District on June 2023. The distribution of cases, high-risk exposure characteristics (contact objects, methods, locations, etc.), incidence characteristics, and medical treatment situation were analyzed. Relevant discussions on epidemic prevention and control were further conducted in light of the actual situation and the problems encountered. Results The cases were all unmarried young men and men who have sex with men (MSM) population. The disease was transmitted from person to person through same-sex contact, with non-fixed sexual partners as the source of infection and exposure locations being relatively concealed, and the average incubation period was 8.42 days. Most cases were discovered through active seeking medical attention, accounting for 68.78% (11/16). Fever was the primary initial symptom accounting for 56.25% (9/16), with the main symptoms being a rash and fever, at 100% and 68.75% (11/16), respectively. Time from fever to rash onset was mainly 0-3 days, accounting for 90.91% (10/11). The eruption site involveed multiple different parts of the body, and there was no special order of eruption. The time interval from onset to seeking medical attention and from onset to discovery was similar, with 5.91 days and 5.94 days respectively. The majority of cases were HIV infected, accounting for 68.75% (11/16)。Conclusions The monkeypox epidemic is prevalent in MSM populations and is transmitted through male to male contact through human transmission. However, due to unstable sexual partners and concealed exposure locations, tracing the source is difficult, with an average incubation period of 8.42 days. The symptoms are mainly fever and rash, with a long time from onset to medical treatment. The initial manifestations are mild, leading to missed diagnoses on the first visit, resulting in difficulty in timely discovery and prevention of further cases. At the same time, investigating and handling the epidemic are challenging, making the prevention and control of the outbreak a difficult task.

Objective:To construct prediction models of necrotizing enterocolitis (NEC) using machine learning (ML) methods.Methods:From January 2015 to October 2021, neonates with suspected NEC symptoms receiving abdominal ultrasound examinations in our hospital were retrospectively analyzed. The neonates were assigned into NEC group (modified Bell's staging≥Ⅱ) and non-NEC group for diagnostic prediction analysis (dataset 1). The NEC group was subgrouped into surgical NEC group (staging≥Ⅲ) and conservative NEC group for severity analysis (dataset 2). Feature selection algorithms including extremely randomized trees, elastic net and recursive feature elimination were used to screen all variables. The diagnostic and severity prediction models for NEC were established using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine and other ML methods. The performances of different models were evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, negative predictive value and positive predictive value.Results:A total of 536 neonates were enrolled, including 234 in the NEC group and 302 in the non-NEC group (dataset 1).70 were in the surgical NEC group and 164 in the conservative NEC group (dataset 2). The variables selected by extremely randomized trees showed the best predictive performance in two datasets. For diagnostic prediction models, the SVM model had the best predictive performance, with AUC of 0.932 (95% CI 0.891-0.973) and accuracy of 0.844 (95% CI 0.793-0.895). A total of 11 predictive variables were determined, including portal venous gas, intestinal dilation, neutrophil percentage and absolute monocyte count at the onset of illness. For NEC severity prediction models, the SVM model showed the best predictive performance, with AUC of 0.835 (95% CI 0.737-0.933) and accuracy of 0.787 (95% CI 0.703-0.871). A total of 25 predictive variables were identified, including age of onset, C-reactive protein and absolute neutrophil count at clincial onset. Conclusions:NEC prediction model established using feature selection algorithm and SVM classification model in ML is helpful for the diagnosis of NEC and grading of disease severity.

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Objective: To study the effects of different concentrated sulfuric acid etching durations on the shear bond strength between polyether-ketone-ketone (PEKK) and dentin, providing a scientific basis for the clinical bonding procedures of PEKK prosthesis. Methods: Forty-four PEKK specimens were prepared and randomly divided into four groups: group A was the control group, which was only polished with abrasive papers, group B, group C and group D were experimental groups, which were etched by 98% concentrated sulfuric acid for 5 s, 30 s and 60 s, respectively. In addition, one sample was randomly selected from each group, and the profile was prepared by a slow cutting machine. The surface morphology of the profile was observed under SEM. After the four groups of specimens and dentin were bonded by resin, they were soaked in distilled water at 37 ℃ for 24 h. After the shear bonding strengths were measured, the fracture interfaces of the specimens were examined by the scanning electron microscopy and stereomicroscopy, and failure models of bonding were analyzed. Results: After acid etching treatments, the cross-sectional images in group B presented uniform spongy shapes, while the cross-sectional images in group C and group D showed destructive pore structures. The shear bond strengths of group B (16.84 ± 1.84) MPa, group C (12.33 ± 1.22) MPa and group D (6.44 ± 1.18) MPa were higher than that of group A (3.99 ± 1.06) MPa (P < 0.05). The highest shear bond strength was observed in group B (16.84 ± 1.84) MPa. Conclusion The surface treatment of 98% sulfuric acid etching for 5 s manifested the best bond strength between PEKK and dentin.

Objective:To investigate the incidence and risk factors of active human cytomegalovirus (HCMV) infection in patients with severe community-acquired pneumonia.Methods:Patients who required respiratory support and were diagnosed with severe community-acquired pneumonia in the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Guangzhou Medical University from March 1, 2019 to June 1, 2020 were consecutively screened and divided into active HCMV infection group (20 cases) and non-active HCMV infection group (95 cases) based on whether a patient has active HCMV infection or not. Differences in demographic data, laboratory findings, and clinical outcomes were compared between the two groups. Moreover, logistic regression was applied to analyze risk factors for active HCMV infection.Results:The 20 of 115 patients with severe community-acquired pneumonia requiring respiratory support were confirmed to have active infection with HCMV, with a prevalence of active HCMV infection of 17.4%. The pneumonia severity index (PSI) and suppressor T lymphocytes (Ts) in active HCMV infection group were higher than that of the control group, and all the differences were statistically significant ( Z=2.432, P=0.015; Z=2.036, P=0.042); whereas lymphocytes, monocytes, blood lactate, and platelet levels were lower than those of the control group, and all the differences were statistically significant ( P < 0.05). Patients with active HCMV infection had a higher transfusion rate than the control group, and the differences were statistically significant (χ 2=3.941; P=0.047). Increasing levels of PSI and Ts percentage were independent risk factors for active HCMV infection ( OR=1.03, 95% CI: 1.01~1.05; OR=1.06, 95% CI: 1.00~1.11; P < 0.05). RICU length of stay, complication rates, and 90-day all-cause mortality were higher in the active HCMV infection group than the control group, and all the differences were statistically significant ( P < 0.05). Conclusions:Active HCMV infection is highly prevalent in patients with severe community-acquired pneumonia and associated with several adverse clinical outcomes, with PSI and Ts cell levels being independent risk factors.

Objective: To observe the effect of medical instant hemostasis gauze combined with filament speed instant gauze on the drainage and flap healing after modified radical mastectomy. Methods: From August 2015 to August 2016, a total of 80 patients with modified radical mastectomy for breast cancer admitted to Huanxing Tumor Hospital, Chaoyang District, Beijing were selected.According to the random number table method, 80 patients who were ready for modified radical mastectomy for breast cancer were randomly divided into study group (40 cases) and control group (40 cases). Two kinds of hemostatic materials (medical hemolytic hemostatic gauze combined with fibril quick hemostatic gauze) were applied to the surgical wounds in the study group during the operation, while no medical hemostatic materials were used in the control group during the operation, and the other treatment was the same as that in the study group.Total drainage volume and drainage tube removal time were compared between the two groups 1 to 5 days after operation. Results: There were no statistically significant differences in the age, body mass index, and effusion production between the two groups (all P>0.05). The total drainage volume of the study group was (289.23±5.36) ml, and the total drainage volume of the control group was (492.15±8.56) ml.The difference between the two groups was statistically significant (t=8.543, P<0.05). The drainage time of the study group was (6.24±1.23) days, and the extraction time of the control group was (10.12±2.21) days.The difference between the two groups was statistically significant (t=6.203, P<0.05). Conclusion In addition to hemostatic function, using absorbable hemostatic gauze combined with surgicel fibrillar during the surgical process can significantly reduce postoperative subcutaneous fluid accumulation.