Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

The increasing prevalence of chronic kidney disease (CKD) is a major global public health concern. Despite the complicated pathogenesis of CKD, renal fibrosis represents the most common pathological condition, comprised of progressive accumulation of extracellular matrix in the diseased kidney. Over the last several decades, tremendous progress in understanding the mechanism of renal fibrosis has been achieved, and corresponding potential therapeutic strategies targeting fibrosis-related signaling pathways are emerging. Importantly, extracellular vesicles (EVs) contribute significantly to renal inflammation and fibrosis by mediating cellular communication. Increasing evidence suggests the potential of EV-based therapy in renal inflammation and fibrosis, which may represent a future direction for CKD therapy.

The perception of motion is an important function of vision. Neural wiring diagrams for extracting directional information have been obtained by connectome reconstruction. Direction selectivity in Drosophila is thought to originate in T4/T5 neurons through integrating inputs with different temporal filtering properties. Through genetic screening based on synaptic distribution, we isolated a new type of TmY neuron, termed TmY-ds, that form reciprocal synaptic connections with T4/T5 neurons. Its neurites responded to grating motion along the four cardinal directions and showed a variety of direction selectivity. Intriguingly, its direction selectivity originated from temporal filtering neurons rather than T4/T5. Genetic silencing and activation experiments showed that TmY-ds neurons are functionally upstream of T4/T5. Our results suggest that direction selectivity is generated in a tripartite circuit formed among these three neurons-temporal filtering, TmY-ds, and T4/T5 neurons, in which TmY-ds plays a role in the enhancement of direction selectivity in T4/T5 neurons.
Animals ; Neurites ; Drosophila ; Neurons ; Connectome

Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.
Animals ; Brain Diseases/therapy* ; Xenotropic and Polytropic Retrovirus Receptor ; Brain/pathology*

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM=11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.

BACKGROUND: Few studies have attempted to compare the differences in the prevalence and impact factors of hysterical tendencies (HTs) in adolescents. Thus, the aim of this study was to examine gender differences in the prevalence and impact factors of adolescents' HTs across three eastern Chinese provinces (Anhui, Jiangsu, and Zhejiang). METHODS: A multicenter, school-based, cross-sectional study was conducted in three provinces (Anhui, Jiangsu, and Zhejiang) in China in 2014. The sample included 10,131 middle-school students aged 13-18 years who were randomly selected using a multiphase, stratified, cluster sampling technique. A two-stage appraisal procedure was used to determine the adolescents' HTs. We also designed a multicenter, school-based, case control (1329 cases with 2661 control individuals) study to collect data on the common factors affecting this population using a common protocol and questionnaire. RESULTS: An overall positive rate of HTs among adolescents across the three eastern Chinese provinces studied was found at 13.1% (95% confidence interval (CI) 12.5-13.8%), at 14.5% (95% CI 13.3-15.7%) for females, and at 12.2% (95% CI 11.1-13.4%) for males. Gender-stratified, multiple conditional regression analyses revealed that superstitious beliefs pertaining to life, somatotype, teacher-student satisfaction, and family achievement orientation were significantly linked to HTs only in males, while left-behind adolescents, emotional and social adaptation, teacher-student support, family cohesion, and the Hospital Anxiety and Depression Scale - depression scores were significantly associated with female HTs only. The models indicated that of all the independent variables studied, family medical history was the strongest impact factor for both male HTs (adjusted matched odds ratio (amOR) = 2.92, 95% CI = 1.84-4.86) and female HTs (amOR = 2.74, 95% CI = 1.59-4.98). CONCLUSIONS HTs are prevalent among adolescents in the three eastern Chinese provinces studied. Gender differences in the prevalence and impact factors of HTs are significant in adolescents, and HTs seem to affect more females than males. Therefore, sex-specific intervention programs against HTs in adolescents should be considered to reduce HT prevalence in adolescents by modifying influential social, school, and family factors.
Adolescent ; Adolescent Behavior ; psychology ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Histrionic Personality Disorder ; epidemiology ; psychology ; Humans ; Male ; Prevalence ; Risk Factors ; Sex Factors ; Students ; psychology

BACKGROUND:Our preliminary findings have shown that stem cells have a certain effect on early formation of renal fibrosis and delay the occurrence of renal interstitial fibrosis.OBJECTIVE:To investigate the effect of exogenous adipose-derived stem cell transplantation on the formation of renal interstitial fibrosis in rats,and to explore the dose-effect relationship.METHODS:Fifty Sprague-Dawley rats were randomly divided into five groups.Rats in sham operation group were injected with PBS;and those in the other four groups were ligated to establish the model of renal fibrosis.After successful modeling,the model group was injected with PBS,while low dose group,middle dose group and high dose group were injected with 1 ×107/L,2x107/L,3x107/L adipose-derived stem cell suspension (0.1 mL),respectively.Rats were killed 14 days after injection.Hematoxylin-eosin staining and Masson staining were used to observe the degree of renal tubular interstitial injury and the relative area of the renal interstitium.Expression of alpha smooth muscle actin and transforming growth factor beta1 was detected by immunohistochemistry.RESULTS AND CONCLUSION:(1) Hematoxylin eosin staining:The model group showed typical glomerular and tubulointerstitial changes;the low,middle and high dose groups had a certain degree of glomerular and tubulointerstitial changes,but the severity of injury in these three groups,especially in the high dose group,was significantly milder than that in the model group.(2) Masson staining:In the model group,the renal interstitium was widened and the collagen fibers were deposited;in the low,middle and high dose groups,the degree of renal interstitial expansion was lower than that in the model group,and moreover,the degree of renal interstitial expansion in the middle and high dose groups was lower than that in the low dose group (P ＜ 0.05).(3) Immunohistochemical staining:Compared with the sham operation group,the expression of alpha smooth muscle actin and transforming growth factor beta1 in the model group was higher than that in the sham operation group (P ＜ 0.05).Compared with the model group,significantly decreased expression of alphasmooth muscle actin was found in the high dose group (P ＜ 0.05) and significantly reduced transforming growth factor beta1 expression was observed in the high,middle,and low dose groups (P ＜ 0.05),especially in the middle and high dose groups.To conclude,exogenous adipose-derived stem cell transplantation can delay the formation of early renal fibrosis in a dose-effect manner,which may be realized by changing the signal pathway state induced by transforming growth factor beta1.