The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Parishin treatment alleviates cardiac aging in naturally aged mice.

Background: Cardiac aging progressively decreases physiological function and drives chronic/degenerative aging-related heart diseases. Therefore, it is crucial to postpone the aging process of heart and create products that combat aging. Aims & methods: The objective of this study is to examine the effects of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata, on anti-aging and its underlying mechanism. To assess the senescent biomarkers, cardiac function, cardiac weight/body weight ratio, cardiac transcriptomic changes, and cardiac histopathological features, heart tissue samples were obtained from young mice (12 weeks), aged mice (19 months) treated with parishin, and aged mice that were not treated. Results: Parishin treatment improved cardiac function, ameliorated aging-induced cardiac injury, hypertrophy, and fibrosis, decreased cardiac senescence biomarkers p16Ink4a, p21Cip1, and IL-6, and increased the "longevity factor" SIRT1 expression in heart tissue. Furthermore, the transcriptomic analysis demonstrated that parishin treatment alleviated the cardiac aging-related Gja1 downregulation and Cyp2e1, Ccna2, Cdca3, and Fgf12 upregulation in the heart tissues. The correlation analysis suggested a strong connection between the anti-aging effect of parishin and its regulation of gut microbiota and metabolism in the aged intestine. Conclusion: The present study demonstrates the protective role and underlying mechanism of parishin against cardiac aging in naturally aged mice.

Joint intention understanding in children with autism spectrum disorder.

This study examined the ability of children with autism spectrum disorder (ASD) to generate joint intention-based action prediction in a joint action task. Children were presented with a series of videos in which two actors either played with blocks based on joint intention (social condition) or played with blocks independently (nonsocial condition). In the familiarization stage, two actors demonstrated how they played with blocks three times. In the test stage, one actor left the scene, and another actor grasped a block and asked where she should place it. Children's gaze behavior was assessed by an eye tracker. After watching videos, children were asked to answer two questions: an action prediction question and an intention understanding question. The results showed that in the implicit eye movement task, children with ASD and typically developing (TD) children exhibited location-based anticipatory gaze under both conditions. However, in terms of explicit behavioral responses, TD children showed higher accuracy in response to action prediction questions and intention understanding questions than children with ASD in the social condition, while no significant group difference was found in the nonsocial condition. These results indicate that children with ASD have difficulty understanding joint intention and that their action prediction is primarily driven by bottom-up sensory inputs.

Inflammatory granuloma of the trachea: a rare case with Epstin-Barr virus infection. / 气管炎性肉芽肿： 1例罕见的EBç— æ¯’æ„ŸæŸ“çš„EBç— æ¯’æ„ŸæŸ“.

Epstein-Barr virus (EBV), a double-stranded DNA virus with an envelope, is a ubiquitous pathogen that is prevalent in humans, although most people who contract it do not develop symptoms (Kerr, 2019). While the primary cells EBV attacks are epithelial cells and B lymphocytes, its target range expands to a variety of cell types in immunodeficient hosts. Serological change occurs in 90% of infected patients. Therefore, immunoglobulin M (IgM) and IgG, serologically reactive to viral capsid antigens, are reliable biomarkers for the detection of acute and chronic EBV infections (Cohen, 2000). Symptoms of EBV infection vary according to age and immune status. Young patients with primary infection may present with infectious mononucleosis; there is a typical triad of symptoms including fever, angina, and lymphadenectasis (Houen and Trier, 2021). In immunocompromised patients, response after EBV infection may be atypical, with unexplained fever. The nucleic acid of EBV can be detected to confirm whether high-risk patients are infected (Smets et al., 2000). EBV is also associated with the occurrence of certain tumors (such as lymphoma and nasopharyngeal carcinoma) because it transforms host cells (Shannon-Lowe et al., 2017; Tsao et al., 2017).

Perforation of the esophagus: an overlooked cause of chest pain as a complication of esophageal foreign bodies. / é£Ÿç®¡ç©¿å­”ï¼šä½œä¸ºé£Ÿç®¡å¼‚ç‰©å¹¶å‘ç—‡å¼•èµ·èƒ¸ç—›çš„ä¸€ä¸ªè¢«å¿½è§†çš„åŽŸå› .

Chest pain is one of the most common complaints in the emergency department. Diseases of the heart, aorta, lungs, esophagus, stomach, mediastinum, pleura, and abdominal viscera can all cause chest discomfort (Gulati et al., 2021; Jiao et al., 2021; Lu et al., 2022). Clinicians in the emergency department are expected to immediately recognize life-threatening chest pain (Jiao et al., 2021). Delayed diagnosis further increases the risk of complications and mortality (Liu et al., 2021). In this case, we present an elderly Chinese female who had a history of myocardial infarction two years previously, with chest pain eventually found to be caused by ingestion of a duck bone.

Parishin alleviates vascular ageing in mice by upregulation of Klotho.

Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.

Alginate Oligosaccharides Enhance Autophagy to Rejuvenate H2O2-Induced Senescent IEC-6 Through the AMPK/mTOR Signaling Pathway.

Intestinal epithelial cellular senescence contributes to the physiological decline of intestine and induces age-associated intestinal diseases. Therefore, the intestine is a vital target to delay intestinal epithelial cellular senescence and extend healthy lifespan. Alginate oligosaccharides (AOSs) have a wide range of biological and pharmacological activities. However, there are no related reports of AOSs on intestinal epithelial cellular senescence. Our study aimed to investigate the effect of AOSs on hydrogen peroxide (H2O2)-induced senescent intestinal epithelial cells (IEC-6) and its antiaging mechanism. A senescent model was successfully constructed by H2O2 (200 µmol/L) treatment on IEC-6 for 4 hours. Different concentrations of AOSs (10, 50, 100 µg/mL) were used to intervene in H2O2-induced senescent IEC-6. The number of ß-galactosidase staining-positive cells was significantly reduced by AOS intervention. The expression levels of p21 and p16, known as the senescent biomarkers, were also decreased. In addition, AOSs alleviated oxidative stress by reducing reactive oxygen species and improving antioxidative ability. To understand how AOSs rejuvenate H2O2-induced senescent IEC-6, we detected the expression level of genes in autophagy process. The results indicated that AOSs restored the expression level of Beclin 1, Atg7, and LC3 to enhance autophagy process by activating activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin in H2O2-induced senescent IEC-6. Compound C, an AMPK inhibitor, abolished the effect of AOSs on activating autophagy and rejuvenating senescent IEC-6. Altogether, our study suggests that AOS is a promising drug for delaying intestinal epithelial cellular senescence.

Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China.

BACKGROUND: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020-2022. METHOD: We collected HIV incidence and mortality data from the website of the National Health Commission of the People's Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020-2022 with those in 2015-2019 using a two-ratio Z-test. RESULTS: From January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015-2019 (pre-COVID-19 stage) and 2020-2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p <  0.001) in 2020-2022 compared with that in 2015-2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p <  0.001), in 2020-2022 compared with those in 2015-2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015-2019, while the incidence during the routine stage in May 2020-December 2022 increased by 27.4334%, (all p <  0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p <  0.001). CONCLUSIONS: The findings suggest that China's dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without China's dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020-2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.

Lactobacillus rhamnosus GG Promotes Recovery of the Colon Barrier in Septic Mice through Accelerating ISCs Regeneration.

Disruption of the intestinal barrier is both the cause and result of sepsis. The proliferation and differentiation of intestinal stem cells (ISCs) promote the regenerative nature of intestinal epithelial cells, repairing the injured intestinal mucosal barrier; however, it is uncertain whether the recovery effects mediated by the ISCs are related to the gut microbiota. This research found that the survival rate of septic mice was improved with a Lactobacillus rhamnosus GG (LGG) treatment. Furthermore, an increased proliferation and decreased apoptosis in colon epithelial cells were observed in the LGG-treated septic mice. In vitro, we found that a LGG supernatant was effective in maintaining the colonoid morphology and proliferation under the damage of TNF-α. Both in the mice colon and the colonoid, the LGG-induced barrier repair process was accompanied by an increased expression of Lgr5+ and lysozyme+ cells. This may be attributed to the upregulation of the IL-17, retinol metabolism, NF-kappa B and the MAPK signaling pathways, among which, Tnfaip3 and Nfkbia could be used as two potential biomarkers for LGG in intestinal inflammation therapy. In conclusion, our finding suggests that LGG protects a sepsis-injured intestinal barrier by promoting ISCs regeneration, highlighting the protective mechanism of oral probiotic consumption in sepsis.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Sex differences in the relationship of serum creatinine to cystatin C ratio and depressive symptoms among middle-aged and older adults in China.

BACKGROUND: Sarcopenia is reported to be associated with depression. Recently, serum creatinine to cystatin C ratio (CCR) has been recommended as a promising biomarker for detecting sarcopenia. The purpose of this study was to explore the relationship between CCR and depressive symptoms among middle-aged and older adults using the baseline data of the China Health and Retirement Longitudinal Study (CHARLS). METHODS: This study included 7083 participants aged 45 and older. A score of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) ≥ 12 was used as the cut-off of having depressive symptoms. CCR was calculated by serum creatinine (mg/dL)/cystatin C (mg/L). The t-test and Chi-squared test were applied to compare the differences between the depressive symptoms group and no depressive symptoms group in both sexes. Unadjusted and adjust logistic regression models were used to further investigate the relationship between CCR and depressive symptoms. RESULTS: In the fully adjusted logistic regression models, higher CCR was significantly correlated with a lower incidence of depressive symptoms in males (OR = 0.486, P = 0.001, 95 % CI = 0.314-0.752), but not in females (OR = 0.775 P = 0.184, 95 % CI = 0.532-1.129). LIMITATIONS: 1. Self-reported method was used to define depressive symptoms by CESD-10; 2. History of chronic diseases were all self-reported; 3. Residual bias was still possible after controlling for many confounding factors. CONCLUSIONS: Lower CCR was significantly correlated with increased depressive symptoms in males, but not in females. More studies are needed to further confirm this conclusion.

Serum creatinine to cystatin C ratio and cognitive function among middle-aged and older adults in China.

Background: The sarcopenia index (SI, serum creatinine/serum cystatin C × 100) is recently suggested to be a reliable marker for sarcopenia. It has been reported that sarcopenia is associated with poorer cognition. The purpose of this study was to evaluate the correlation between SI and cognitive function among middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). Materials and methods: A total of 6,442 participants ≥45 years of age were enrolled in this study from CHARLS between 2011 and 2012. Cognitive function was assessed by interview-based measurements, including orientation and attention, episodic memory, visuo-construction, and the total cognitive function. SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L) × 100. One-way analysis of variance (ANOVA) was used to compare the differences among groups divided according to SI quartiles by gender. Both linear and logistic regression models were applied to investigate the relationship between SI and cognitive function. Results: After adjustment for potential confounders, we found SI was significantly and positively correlated with total cognitive function scores both in males and females [ß = 0.014, 95% confidence interval (CI) 0.007 to 0.021, P < 0.001; ß = 0.011, 95 CI% 0.003 to 0.018, P = 0.004; respectively]. Similarly, when the total cognitive function score was treated as a categorical variable according to quartiles in males and females, higher SI was related to better total cognitive function scores in both males and females [odds ratio (OR) = 1.147, 95% CI 1.028 to 1.279, P = 0.014; OR = 1.219, 95% CI 1.106 to 1.344, P < 0.001; respectively] following adjustment for confounders. Conclusions: Lower sarcopenia index was correlated with a higher prevalence of cognitive impairment among middle-aged and older adults in China.

Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis.

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

Prognostic value of sarcopenia in patients with rectal cancer: A meta-analysis.

BACKGROUND: Sarcopenia is usually characterized by the loss of skeletal muscle mass and impaired muscle function which is commonly seen in the elderly. It has been found to be associated with poorer prognoses in many types of cancer. Computed tomography (CT) scan is frequently used to assess skeletal muscle mass and further calculate skeletal muscle index (SMI) at the third lumbar vertebra level (L3), which is used to define sarcopenia. The purpose of this meta-analysis was to assess the prognostic value of sarcopenia for overall survival (OS) in patients with rectal cancer. METHODS: We performed a systematic search to find relevant studies published up to 14 January 2021 in PubMed, Embase, Web of science and Scopus. In our meta-analysis, studies comparing OS in rectal cancer patients with sarcopenia versus those without were included. Quality assessment for included studies was evaluated according to the Quality in Prognosis Studies (QUIPS) tool. We directly extracted hazard ratios (HRs) with 95% confidence intervals (CIs) in both univariate and multivariate analyses from each study. The Cochrane Collaboration's Review Manager 5.4 software was applied to analyze data. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and website GRADEpro. RESULTS: Finally, a total of 7 studies involving 2377 patients were included. The pooled HRs were 2.10 (95% CI 1.33-3.32, P = 0.001) and 2.37 (95% CI 1.13-4.98, P = 0.02) using random-effects models in univariate and multivariate analyses, respectively. The results showed a significant association between sarcopenia and OS in patients with rectal cancer. The quality of the evidence for OS was moderate for both univariate and multivariate analyses. CONCLUSION: CT-defined sarcopenia is an independent predictor for worse OS in patients with rectal cancer. Future studies with a more stringent definition of sarcopenia are required to further confirm our findings.

Parishin From Gastrodia Elata Ameliorates Aging Phenotype in Mice in a Gut Microbiota-Related Manner.

The physiological and pathological processes that accompany aging can seriously affect the quality of life of the elderly population. Therefore, delaying aging and developing antiaging products have become popular areas of inquiry. Gut microbiota plays an important role in age-related phenotypes. The present study aimed to investigate the antiaging effects and underlying mechanism of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata. Samples from adult (12 weeks), low-dose (10 mg/kg/d) or high-dose (20 mg/kg/d) parishin-treated and untreated aged (19 months) mice were collected to determine blood indicators, gut microbiota and metabolome, and cardiopulmonary histopathological features. The results showed that parishin treatment ameliorates aging-induced cardiopulmonary fibrosis and increase in serum p16 Ink4a , GDF15, and IL-6 levels. Furthermore, parishin treatment alleviated dysbiosis in gut microbiota, including altered microbial diversity and the aberrant abundance of opportunistic pathogenic bacteria such as Turicibacter and Erysipelatoclostridium. Gene function prediction and gut metabolome analysis results indicated that the parishin treatment-altered gut microbiota played important roles in sugar, lipid, amino acid and nucleic acid metabolism, and improved gut metabolic disorders in aged mice. In conclusion, the present study provides an experimental basis of potential applications of parishin against aging.

Validation of the bodily expressive action stimulus test among Chinese adults and children.

The bodily expressive action stimulus test (BEAST) is developed to provide a set of standardized emotional stimuli for experimental investigations of emotion and attention, and the consistency has been validated in adult populations abroad. However, the consistency of this test in the Chinese population is unclear. To this end, 42 images of each category of emotion (happiness, sadness, fear, and anger) were selected from 254 images of the original stimulus set to further examine the consistency of the BEAST in Chinese population. Thirty-one Chinese college students and 41 Chinese preschool children participated in this study. All of them were asked to complete an emotion recognition and judgment task. Results showed that adults had a high degree of consistency in rating these pictures, while the children's consistency was at a medium level. For adults, sadness was the easiest to recognize, followed by fear and anger, while happiness was the hardest to recognize. For children, fear was the easiest to recognize, anger and sadness were second, and happiness was also the hardest to recognize. At the same time, adults were more accurate in identifying happiness and sadness than children. For adults, they were more likely to confuse positive emotions with negative emotions. They tended to mistake sadness, fear, and anger for happiness. For children, they were more likely to identify sadness as fear and happiness. They also tended to recognize anger as fear. These results indicate that the recognition performance of BEAST images for Chinese and Western adults are roughly the same, however, in the same cultural context, the recognition performance of adults and children are very different, and generally the recognition accuracy rate of adults is higher than that of children.