Transcranial temporal interference stimulation (tTIS) is a novel non-invasive transcranial electrical stimulation technique that achieves deep brain stimulation through multiple electrodes applying electric fields of different frequencies. Current studies on the mechanism of tTIS effects are primarily based on rodents, but experimental outcomes are often significantly influenced by electrode configurations. To enhance the performance of tTIS within the limited cranial space of rodents, we proposed various electrode configurations for tTIS and conducted finite element simulations using a realistic mouse model. Results demonstrated that ventral-dorsal, four-channel bipolar, and two-channel configurations performed best in terms of focality, diffusion of activated brain regions, and scalp impact, respectively. Compared to traditional transcranial direct current stimulation (tDCS), these configurations improved by 94.83%, 50.59%, and 3 514.58% in the respective evaluation metrics. This study provides a reference for selecting electrode configurations in future tTIS research on rodents.
Animals ; Transcranial Direct Current Stimulation/instrumentation* ; Electrodes ; Mice ; Computer Simulation ; Finite Element Analysis ; Brain/physiology*

Objective To assess the utility of real-time shear wave elastography(SWE)in diagnosing vascular erectile dysfunction(ED)and to predict the optimal timing for color Doppler flow imaging(CDFI)examination.Methods Patients diagnosed with ED who received intracavernosal injection(ICI)of vasoactive drugs were recruited and categorized based on CDFI findings into three groups:arterial ED(n=17),venous ED(n=33),and non-vascular ED(n=29).SWE technology was utilized to measure the average Young's modulus(E value)of the corpus cavernosum in these patients,both in the flaccid state prior to ICI and at four time points following ICI-induced erection.Subsequently,the differences in E values among the three groups were analyzed.Results There was no significant difference in the E value of the corpus cavernosum in the flaccid state among the arterial,venous,and non-vascular ED groups before ICI(P>0.05).However,the E value in the flaccid state for each group was significantly higher than the mean E values observed at the four time points after ICI-induced erection(P<0.01).Additionally,the mean E values at these four time points post-ICI were also statistically significant(P<0.01).ROC curve analysis revealed that the AUC for diagnosing arterial,venous,and non-vascular ED using the E value after ICI were 0.814,0.770,and 0.711,respectively,with corresponding cutoff values of 9.98,8.16 and 7.06 kPa.The combined use of CDFI and SWE cutoff values following ICI-induced erection significantly shortened the detection time for both arterial and venous ED groups(P<0.01).Conclusions SWE can accurately measure the E value of the corpus cavernosum following erection induced by the vasoactive drug ICI,thereby facilitating the differentia-tion of various types of ED.Additionally,when combined with CDFI,this technique can reduce the time required for examination.

Objective To assess the utility of real-time shear wave elastography(SWE)in diagnosing vascular erectile dysfunction(ED)and to predict the optimal timing for color Doppler flow imaging(CDFI)examination.Methods Patients diagnosed with ED who received intracavernosal injection(ICI)of vasoactive drugs were recruited and categorized based on CDFI findings into three groups:arterial ED(n=17),venous ED(n=33),and non-vascular ED(n=29).SWE technology was utilized to measure the average Young's modulus(E value)of the corpus cavernosum in these patients,both in the flaccid state prior to ICI and at four time points following ICI-induced erection.Subsequently,the differences in E values among the three groups were analyzed.Results There was no significant difference in the E value of the corpus cavernosum in the flaccid state among the arterial,venous,and non-vascular ED groups before ICI(P>0.05).However,the E value in the flaccid state for each group was significantly higher than the mean E values observed at the four time points after ICI-induced erection(P<0.01).Additionally,the mean E values at these four time points post-ICI were also statistically significant(P<0.01).ROC curve analysis revealed that the AUC for diagnosing arterial,venous,and non-vascular ED using the E value after ICI were 0.814,0.770,and 0.711,respectively,with corresponding cutoff values of 9.98,8.16 and 7.06 kPa.The combined use of CDFI and SWE cutoff values following ICI-induced erection significantly shortened the detection time for both arterial and venous ED groups(P<0.01).Conclusions SWE can accurately measure the E value of the corpus cavernosum following erection induced by the vasoactive drug ICI,thereby facilitating the differentia-tion of various types of ED.Additionally,when combined with CDFI,this technique can reduce the time required for examination.

A 63-year-old maintenance hemodialysis patient with diabetic nephropathy was reported. The patient was incapacitated, with systemic edema, heart failure, severe anemia, malnutrition, gastrointestinal bleeding, and intractable hypertension. We adopted integrated management methods such as "multidisciplinary collaboration" and "doctor-patient collaboration": by accurately controlling the volume load to protect the residual renal function, taking into account the treatment of underlying diseases and complications, integrating the clinical parameters of dialysis and the interdialysis period, and combining the subjective clinical symptom score with the objective index analysis, the objectives of effectively controlling the dry weight of patients, alleviating complications, improving nutrition and protecting the residual renal function were finally achieved. The quality of life of the patient had been significantly improved.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Objective To investigate the differences in the influencing factors for acute necrotizing pancreatitis (ANP) and infectious pancreatic necrosis (IPN) between Eastern and Western countries, and to provide a theoretical basis for the prediction and prevention of ANP. Methods Databases including PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles on the influencing factors for ANP and IPN published up to January 21, 2021, and a Meta-analysis was performed. Results A total of 59 studies were included, with 22 studies from Eastern countries and 37 studies from Western countries.The Meta-analysis showed that in Eastern countries, male sex (odds ratio[ OR ]=1.51, 95% confidence interval[ CI ]: 1.18-1.91, P < 0.01), C-reactive protein (CRP)(standardized mean difference[ SMD ]=1.39, 95% CI : 1.06-1.71, P < 0.01), D-dimer ( SMD =0.44, 95% CI : 0.07-0.81, P =0.02), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score (mean difference[ MD ]=3.51, 95% CI : 1.38-5.64, P < 0.01), alcoholic etiology ( OR =3.57, 95% CI : 2.68-4.75, P < 0.01), and biliary etiology ( OR =0.60, 95% CI : 0.46-0.77, P < 0.01) were the influencing factors for ANP, and in Western countries, male sex ( OR =1.63, 95% CI : 1.30-2.05, P < 0.01), CRP ( SMD =2.09, 95% CI : 1.12-3.05, P < 0.01), APACHE-Ⅱ score ( MD =4.28, 95% CI : 2.73-5.83, P < 0.01), Ranson score ( MD =2.99, 95% CI : 2.50-3.47, P < 0.01), and organ failure ( OR =10.87, 95% CI : 2.62-45.04, P < 0.01) were the influencing factors for ANP.In Eastern countries, age ( MD =2.16, 95% CI : 0.43-3.89, P =0.01), body mass index (BMI)( MD =1.74, 95% CI : 1.23-2.25, P < 0.01), albumin level ( SMD =-0.43, 95% CI : -0.75 to-0.12, P < 0.01), CRP ( SMD =0.58, 95% CI : 0.04-1.11, P =0.03), procalcitonin ( SMD =0.80, 95% CI : 0.56-1.04, P < 0.01), D-dimer ( MD =0.23, 95% CI : 0.15-0.31, P < 0.01), APACHE-Ⅱ score ( MD =2.47, 95% CI : 0.73-4.22, P < 0.01), Ranson score ( MD =1.60, 95% CI : 1.46-1.73, P < 0.01), and extent of necrosis ≥30%( OR =2.52, 95% CI : 1.26-5.06, P < 0.01) were the influencing factors for IPN, while in Western countries, age ( MD =4.07, 95% CI : 1.82-6.31, P < 0.01), APACHE-Ⅱ score ( MD =3.28, 95% CI : 1.39-5.17, P < 0.01), Ranson score ( MD =2.18, 95% CI : 1.75-2.62, P < 0.01), SIRS score ( OR =3.88, 95% CI : 1.58-9.51, P < 0.01), alcoholic etiology ( OR =0.61, 95% CI : 0.42-0.87, P < 0.01), and organ failure ( OR =3.63, 95% CI : 1.11-11.92, P =0.03) were the influencing factors for IPN. Conclusion Current evidence shows that biliary etiology and alcoholic etiology are unique influencing factors for ANP in the Eastern population, while Ranson score is a unique influencing factor in the Western population.BMI and extent of necrosis ≥30% are unique influencing factors for IPN in the Eastern population, while alcoholic etiology is a unique influencing factor in the Western population.

Objective To evaluate the association between short-term exposure to air pollutants of end-stage renal disease(ESRD)patients on maintenance hemodialysis and the number of daily hospital admissions.Methods The data on hospitalizations were obtained from the database of the municipal Urban Employees'Basic Medical Insurance and Urban Residents'Basic Medical Insurance of a city in Southwest China.Single and multiple pollutant generalized additive models were utilized to estimate the effect of air pollutants(CO,NO2,O3,PM10,PM25,and SO2)on patient admissions after the lag time of different numbers of days.In addition,subgroup analyses stratified by sex,age,PM25 and PM10 concentration thresholds,seasonality,and comorbidity status for cardiovascular diseases and hypertension were conducted.Results In the single pollutant models,the pollutants significantly associated with patient admissions and the corresponding lag time of the strongest association were as follows,every time CO increased by 0.1 mg/m3,there was a 2.39％increase(95％confidence interval[CI]:0.96％-3.83％)in patient admissions after 7 days of lag time;every time NO2,O3,PM2.5,PM10,and SO2 increased by 10 μg/m3,patient admissions increased by 4.02％(95％CI:1.21％-6.91％)after 7 days of lag time,3.57％(95％CI:0.78％-6.44％)after 0-4 days of lag time,2.00％(95％CI:1.07％-2.93％)after 6 days of lag time,1.19％(95％CI:0.51％-1.88％)after 7 days of lag time,and 8.37％(95％CI:3.08％-13.93％)after 7 days of lag time,respectively.In the multiple pollutant model,every time O3 and PM2.5 increased by 10 μg/m3,there was an increase of 3.18％(95％CI:0.34％-6.09％)in daily patient admissions after 0-4 days of lag time and an increase of 1.85％(95％CI:0.44％-3.28％)after 7 days of lag time.Furthermore,subgroup analyses showed that seasonality,the severity of air pollution,and patients'comorbidities might be the effect modifiers for the association between ambient air pollution and hospital admissions in ESRD patients receiving maintenance hemodialysis.Conclusion Air pollution is closely associated with hospital admissions in ESRD patients undergoing maintenance hemodialysis and the strength of this association varies according to seasonality,the severity of air pollution,and patients'status of comorbidities.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

Background Long working hours (LWH) and shift work are harmful to the physical and mental health of occupational groups. Objective To understand the status quo of LWH and shift work of migrant workers in Shanghai, and to analyze the influence of the above two factors on sleep of the population. Methods From July to September 2018, a cross-sectional survey using questionnaires was conducted among 3215 in-service employees at seven workplaces with more than 300 employees in six selected districts of Shanghai using multi-stage random sampling method. A total of 2976 valid questionnaires were collected, with a valid response rate of 92.6%. The questionnaires included general demographic characteristics, personal health behavior, work-related factors, weekly working hours, shift work, and sleep. Univariate analysis and logistic regression analysis were used to investigate the relationships of LWH and shift work with sleep, and an interaction item was included to evaluate potential interaction between LWH and shift work. Result The average age of the subjects was (30.98±9.49) years old, the male to female ratio was 1∶1.20, and 2382 workers were reported without local residency (80.0%). Among the migrant workers, the average weekly working hours was (57.23±13.14) h, the proportions of LWH (weekly working hours>40 h), extra LWH (weekly working hours>55 h), and shift work were 80.6% (1919/2382), 60.3% (1436/2382), and 25.4% (600/2366), respectively, all above were significantly higher than those of local workers. The prevalence rates of insomnia and lack of sleep among the migrant workers were 46.3% (1091/2356) and 25.4% (597/2354), respectively. The results of logistic regression model showed that after adjusting demographic characteristics such as gender, age, education level, and monthly income, as well as occupation and personal health behavior, compared with working hours ≤40 h per week, working 55-60 h per week was a risk factor for insomnia of migrant workers (OR=1.33, 95%CI: 1.02-1.72), while working >60 h per week was a risk factor for both insomnia (OR=1.37, 95%CI: 1.05-1.78) and insufficient sleep (OR=1.73, 95%CI: 1.28-2.35) of migrant workers. Shift work was only associated with insomnia (OR=1.37, 95%CI: 1.11-1.69). Meanwhile, working hours>60 h per week and shift work had an interaction effect on insomnia of migrant workers (OR=2.35, 95%CI: 1.20-4.60). Conclusion LWH and shift work are prominent among migrant workers, and there is an interaction between LWH and shift work with insomnia.

Background The community is the main place for people's daily activities. A livable environment will improve the subjective well-being of residents. Objective To understand the current status of subjective well-being of residents in Pudong, Shanghai, and explore the impact of community environmental factors on residents' subjective well-being. Methods Using quota sampling, 6000 permanent residents from 12 sub-districts or towns in Pudong, Shanghai were selected to participate in an questionnaire survey. The questionnaire included three parts: participants' basic information, community environmental factors (neighborhood aesthetics, fitness environment, public service and security, natural environment), and subjective well-being. Using a multiple regression model, the influence of community environmental factors on the subjective well-being of residents was analyzed. Results A total of 5887 questionnaires were recovered, and the valid recovery rate was 98.1%. The subjective well-being score of the survey respondents was (7.03±1.61) points. There was no statistical difference in the subjective well-being score of study subjects of different gender and marital status groups; while those with different ages, education levels, occupations, and self-evaluated economic status showed statistical differences in their subjective well-being score (P<0.05). The multiple logistic regression analysis results showed that after controlling general demographic characteristics, with the low level as the control group (according predetermined cut-off values of 33.3% and 66.7%, the community environmental factors were divided into high-, medium-, and low-level groups), the OR values of subjective well-being of the high- and medium-level neighborhood aesthetics groups were 1.393 (95%CI: 1.173-1.654) and 1.235 (95%CI: 1.080-1.412); the OR values of the high- and medium-level fitness environment groups were 2.297 (95%CI: 1.929-2.734) and 1.349 (95%CI: 1.166-1.560); the OR values of the high- and medium-level public service and security groups were 1.101 (95%CI: 0.943-1.285) and 1.039 (95%CI: 0.905-1.193); the OR values of the high- and medium-level natural environment groups were 4.248 (95%CI: 3.321-5.434) and 1.652 (95%CI: 1.374-1.986), respectively. Conclusion Community environment factors could affect residents' subjective well-being, and good neighborhood aesthetics, fitness environment, natural environment have positive effects.