The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

ObjectiveTo investigate the relationship between mosquito density fluctuations and meteorological factors, so as to provide a scientific basis for mosquito surveillance analysis, risk assessment, and comprehensive prevention and control. MethodsMosquito surveillance and monitoring data of 2020‒2023 was obtained from on-site supervisory sampling by Songjiang Center for Disease Control and Prevention, and meteorological data was obtained from the Wheat A wheat malt-agro-meteorological big data system. Excel 2019 and SPSS 25.0 software were used to organize and analyze the mosquito number, species composition, and seasonal changes in mosquito density captured by the CO₂-light trap at rach monitoring site. Circular distribution method was used to calculate the peak time of mosquito density, combined with the meteorological data of the same period to explore the impact of meteorological factors on the results of mosquito surveillance. ResultsThere was a statistical difference in the overall distribution of mosquito quantity in different habitats(H=23.11, P<0.05), 2020‒2023. In addition, the results showed that July 28th was the peak day for mosquito density, and the duration from June 13th to September 11th was the seasonal peak period for mosquitoes. Pearson correlation analysis showed a positive correlation between mosquito density and average air temperature, average highest air temperature, average lowest air temperature, extreme maximum air temperature, extreme minimum air temperature, precipitation, and number of precipitation days (all P<0.01). While, there was no significant correlation between average wind speed and mosquito density (P>0.05). Multiple stepwise regression analysis resulted in the equation of Y=0.151X_{extreme minimum temperature}+0.321X_{number of precipitation days}+1.002X_{SQRT precipitation}-1.288 (F=102.635, P<0.05). ConclusionThe CO₂-light trap is advisable to monitor the habitats of farmers, livestock sheds, residential areas, parks, hospitals, and other external environments. Air temperature and precipitation have a significant impact on mosquito density. It is recommended to implement comprehensive prevention and control measures to reduce mosquito density and prevent mosquito-borne diseases before the peak period of mosquitoes.

Objective To explore the alterations in gray matter volume(GMV)in adolescents with bipolar disorder(BD).Methods 36 BD patients(BD group)and 37 healthy controls(HC group)who underwent magnetic resonance imaging(MRI)for artificial visual inspection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University from September 2019 to December 2021 were selected.Structural MRI data were processed by using FreeSurferv6.0.0,and statistical analysis were conducted by using SPSS 26.0 and R language software.Receiver operating characteristic(ROC)curve were employed to assess the diagnostic efficacy of various brain regions.Results Compared to HC group,patients in BD group exhibited significant reductions in GMV in the right superior frontal gyrus,right nucleus accumbens,left insula,right lateral orbitofrontal cortex,and right medial orbitofrontal cortex(P＜0.05).ROC curve analysis indicated that area under the curve(AUC)for the right superior frontal gyrus and right nucleus accumbens were 0.739 and 0.712 respectively,while the combined AUC for multiple brain regions was 0.820.Conclusion Adolescents with BD show significant reductions in GMV in specific brain regions,provide reference for the early identification and pathological mechanism research of BD.

Objective:To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia.Methods:The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women′s Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed.Results:(1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds ( P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions:Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

Objective:To compare the characteristics of gait disorders between patients with idiopathic normal pressure hydrocephalus(iNPH)and Parkinson's disease(PD)patients.Methods:General clinical data and gait assessment results of 16 iNPH patients, 20 PD patients, and 23 healthy adults seeking treatment at Tianjin Huanhu Hospital between January 2020 and December 2020 were retrospectively analyzed.Gait analysis was conducted using the Mobility Lab? system with APDM Opal sensors from the US.Results:The 16 patients in the iNPH group had a mean age of(68.81±8.73), the 20 patients in the PD group had a mean age of(65.05±10.15), and the 23 adults in the control group had a mean age of(59.96±6.20).There was no significant difference in age between the iNPH group and the PD group( P>0.05).However, the iNPH group was older than the healthy control group( t=3.71, P<0.05).The disease duration of the iNPH group was(22.94±23.19)months, which was shorter than(92.60±53.70)months in the PD group( t=5.23, P<0.05).The mini-mental state examination(MMSE)score(17.13±7.08)and the Montreal Cognitive Assessment(MoCA)score(11.75±5.43)of the iNPH group were significantly lower than those in the PD group[(24.17±4.73), t=3.45, P<0.05、(21.29±5.82), t=4.86, P<0.05]and the control group[(26.70±1.61), t=5.31, P<0.05、(22.78±3.30), t=7.89, P<0.05].Compared with the PD group, the iNPH group had a significantly lower foot clearance[right: (1.65±0.76)cm vs.(2.56±1.30)cm]and smaller bilateral toe-off angles[left: (20.59±6.11)° vs.(28.43±6.36)°; right: (20.78±6.88)° vs.(28.12±7.49)°, t=3.74、3.02, respectively, all P<0.05].There were statistically significant differences in all gait parameters in iNPH patients compared with the control group( P<0.05). Conclusions:iNPH patients exhibit clear gait disturbance, which is more prominent than in PD patients.The wearable gait analysis system can accurately assess gait disorders in iNPH patients, and can be applied to gait assessment and the development of rehabilitation plans.

Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Objective To investigate the relationship between serum levels of long non-coding RNA(ln-cRNA)nuclear-enriched abundant transcript 1(NEAT1)and microRNA miR-23c in patients with diabetic ne-phropathy(DN).Methods A total of 136 DN patients admitted to the hospital from May 2019 to May 2020 were enrolled in the study as the DN group.Fifty-eight healthy people who underwent physical examination in the hospital during the same period were enrolled as the control group.Real-time fluorescence quantitative PCR(qPCR)was used to detect serum lncRNA NEAT1,miR-23c,kidney injury molecule-1(KIM-1),neutro-phil gelatinase-associated lipocalin(NGAL),tumor necrosis factor-α(TNF-α)mRNA and interleukin-6(IL-6)mRNA in the two groups.Pearson/Spearman correlation was used to analyze the correlation of serum ln-cRNA NEAT1 and miR-23c with KIM-1,NGAL,TNF-α,IL-6 mRNA levels and eGFR in DN patients.DN pa-tients were divided into different CKD stages,and the levels of serum lncRNA NEAT1,miR-23c,KIM-1,NGAL,TNF-α,and IL-6 mRNA in patients in different CKD stages were compared.Multivariate ordered Lo-gistic regression was used to analyze whether serum levels of lncRNA NEAT1 and miR-23c were influencing factors for the progression of DN.Results Compared with the control group,the serum levels of lncRNA NEAT1,KIM-1,NGAL,TNF-α and IL-6 mRNA in the DN group were increased,while miR-23c and esti-mated glomerular filtration rate(eGFR)were decreased,and the differences were all statistically significant(P＜0.05).The serum levels of lncRNA NEAT1,KIM-1,NGAL,TNF-α and IL-6 mRNA in DN patients in G1-G5 stages were increased in order,and the level of miR-23c was decreased in order(P＜0.05).Serum ln-cRNA NEAT1 in DN patients was positively correlated with KIM-1,NGAL,TNF-α and IL-6 mRNA levels(P＜0.05),and negatively correlated with miR-23c and eGFR(P＜0.05).The level of serum miR-23c was negatively correlated with the mRNA levels of KIM-1,NGAL,TNF-α and IL-6(P＜0.05),and positively cor-related with eGFR(P＜0.05).lncRNA NEAT1(OR=2.177,95％CI:2.113-2.441)was an independent risk factor for DN progression,while miR-23c(OR=0.595,95％CI:0.543-0.726)was an independent pro-tective factor(P＜0.05).Conclusion Elevated serum lncRNA NEAT1 levels and reduced miR-23c levels in DN patients are closely associated with the progression of DN disease.

Objective:To investigate the professional identity status of nursing students in higher vocational colleges in Shanghai, China, and to analyze the influencing factors.Methods:By cluster sampling, we selected 308 nursing students of grade 2019 from a higher vocational college in Shanghai for a survey with the General Information Questionnaire, Professional Identity Questionnaire for Nurse Students (PIQNS), Stanford Presenteeism Scale-6 (SPS-6), Wong and Law Emotional Intelligence Scale (WLEIS), Workplace Social Capital (WSC), and Nurse Psychological Capital Questionnaire (PCQ). SPSS 22.0 was used for descriptive analysis, the independent samples t-test, one-way analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results:The total PIQNS score of the students was (64.93±12.83), the total SPS-6 score was (15.91±4.40), the total WLEIS score was (80.57±15.52), the total WSC score was (32.38±6.33), and the total PCQ score was (95.47±18.63). The PIQNS score was negatively correlated with the SPS-6 score ( r=-0.282, P<0.01), positively correlated with the WLEIS score ( r=0.712, P<0.01), positively correlated with the WSC score ( r=0.659, P<0.01), and positively correlated with the PCQ score ( r=0.681, P<0.01). The multiple linear regression analysis showed that personal interest, emotional intelligence, and psychological capital significantly affected the professional identity of nursing students, entering the regression equation for professional identity. Conclusions:The professional identity of higher vocational nursing students in Shanghai is at a medium level, and personal interest, emotional intelligence, and psychological capital are the main factors influencing professional identity.

One case of COVID-19 infection secondary to pulmonary mucormycosis in a recipient of simultaneous pancreas-kidney transplantation was described. Early identification of the pathogen was achieved by metagenomic next-generation sequencing. On the basis of disease status and liver function changes, targeted treatments included intravenous amphotericin B liposome, amphotericin B nebulization& gargling and subsequently a maintenance therapy of oral posaconazole. This regimen resulted in the absorption of lung infection, stabilization of transplanted pancreas function and reduced levels of creatinine and urea as compared to pre-infection period. The therapeutic efficacy was decent.