BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Neuropeptide Y receptor Y8(NPY8R)is a fish-specific receptor with two subtypes,NPY8AR and NPY8BR.Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation;this has been found in only a few fish,at present.In order to better understand the physiological function of npy8br,especially in digestion,we used clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)technology to generate npy8br-/-Japanese medaka(Oryzias latipes).We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability,ultimately affecting their growth.Specifically,npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes(npy and agrp).npy8br-/-medaka larvae fed for 10 d(10th day of feeding)still had incompletely digested brine shrimp(Artemia nauplii)in the digestive tract 8 h after feeding,the messenger RNA(mRNA)expression levels of digestion-related genes(amy,lpl,ctra,and ctrb)were significantly decreased,and the activity of amylase,trypsin,and lipase also significantly decreased.The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes(gh and igf1).Hematoxylin and eosin(H&E)sections of intestinal tissue showed that npy8br-/-medaka larvae had damaged intestine,thinned intestinal wall,and shortened intestinal villi.So far,this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.

Objective To invesigate the feasibility of low radiation dose and low contrast dosage in triple-rule-out computed tomo-graphy angiography(TRO-CTA)on the 320-row detector CT.Methods A total of 120 patients who underwent CTA were prospec-tively selected.All patients were divided into control group(n=90)and experimental group(n=30).The control group employed standard-doses protocol of pulmonary CTA(120 kV tube voltage,45 mL contrast dosage),coronary CTA(120 kV,50-60 mL),and aortic CTA(120 kV,75 mL),while the experimental group received TRO-CTA with 100 kV and 70-80 mL.The peak time of contrast dosage at the pulmonary artery and aorta was measured by low-dose detection method in the experimental group,and the contrast examination was performed sequentially in the control group.Subjective scores and objective image quality of the pulmonary artery,coronary artery,and aorta in the experimental group and the control group were measured and compared,respectively.The effective dose(ED)between the two groups were recorded and compared.Independent samples t-test and Fisher exact probability were used to analyze the statistical differences between the above measures.Results There were no significant differences in CT values,con-trast-to-noise ratio(CNR),signal-to-noise ratio(SNR)of pulmonary artery,coronary artery and aorta between the two groups(P＞0.05).The mean subjective scores of pulmonary artery,coronary artery and aorta segments in the two groups were not less than 3 points,meeting the requirement of clinical diagnosis.There was no statistical difference in subjective scores between the two groups(P＞0.05).There was statistically significant difference in ED between the two groups(P＜0.05).The ED of pulmonary artery,coronary artery,and aorta in the experimental group were 11.49％,13.33％,and 11.46％significantly lower than those in the control group,respec-tively.Conclusion It is feasible to obtain TRO-CTA images used by the low radiation dose and low contrast dosage on the 320-row detector CT,and radiation dose and contrast dosage can be reduced reasonably without alterations of TRO-CTA images quality in clinical practice.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Objective:To study the effect of blood volume feedback control system on improving intradialytic-hypotension (IDH) in maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. Thirty MHD patients with recurrent IDH in the Dialysis Center of the First Affiliated Hospital of Zhejiang University School of Medicine from March 2021 to March 2022 were selected. A self-control study was conducted in MHD patients. The patients were treated with routine hemodialysis in both baseline phase (A1) and reversal phase (A2), while with hemodialysis under the blood volume feedback control system in intervention phase (B). Each phase lasted for 4 weeks (12 hemodialysis sessions). The average occurrences of IDH and IDH-related adverse events (IDH-RAE, stopping dehydration for more than 10 minutes or getting off the hemodialysis machine 10 minutes earlier due to IDH) of each patient between phase A1, B, and A2 were calculated and compared. In a total of 1 080 dialysis records, a logistic regression analysis model was established with age, sex and intervention as independent variables and with the occurrence of IDH-RAE as the outcome.Results:A total of 30 eligible patients were included in the study, including 14 males (46.7%) and 16 females (53.3%), aged 63.0 (56.5, 72.5) years old, with a median dialysis age of 84.0 (37.2, 120.0) months. The average times of IDH in 30 MHD patients decreased from 1.17 (0.83, 1.67) in stage A1 (before intervention) to 0.33 (0.25, 0.58) in stage B (after intervention) ( P<0.05). The frequency of IDH-RAE decreased significantly from 0.29 (0.19, 0.47) in stage A1 to 0.17 (0,0.25) in stage B ( P<0.05). Logistic regression analysis results indicated that the use of blood volume feedback control system reduced the risk of IDH-RAE by 53% ( OR=0.47, 95% CI 0.34-0.64, P<0.001). Conclusions:The application of blood volume feedback control system can effectively reduce the occurrences of IDH and the risk of IDH-RAE in MHD patients.

Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.

【Objective】 To investigate the effect of multiple apheresis platelet donation on platelet indexes and aggregation function in platelet donors, and to analyze the relationship between platelet indexes and their relationship with platelet aggregation rate. 【Methods】 A total of 83 platelet donors were randomly selected from Foshan Central Blood Station from September 2021 to October 2022, and were divided into control group (n= 9, first-time platelet donors or donors with the time interval from the last platelet donation >1 year) and study group (n= 74, repeat platelet donors or donors with the time interval from the last platelet donation ≤ 1 year) according to the times of blood donation. The study group was divided into 4 subgroups: 2-5 times group, 6-10 times group, 11-15 times group and 16 times group. The platelet count(Plt), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), and maximum platelet aggregation rate (MAR) before donation in each group were detected and analyzed. 【Results】 There were no significant differences in Plt, MPV, PDW, P-LCR and MAR between the subgroups and the control group (P>0.05), and there were no significant differences in Plt, MPV, PDW, P-LCR and MAR between each subgroup (P>0.05) .There was a positive correlation between Plt and MAR in blood donors (P<0.05), and the correlation coefficient was 0.445. MPV, PDW and P-LCR were negatively correlated with MAR (P<0.05), and the correlation coefficients were -0.282, -0.233 and -0.217, respectively. Plt was negatively correlated with MPV, PDW and P-LCR (P < 0. 05), and the correlation coefficients were -0.399, -0.307 and -0.339, respectively. MPV, PDW and P-LCR are positively correlated with each other. The correlation coefficient between MPV and PDW was 0.792, that between MPV and P-LCR was 0.863, and tthat between PDW and P-LCR was 0.817. 【Conclusion】 There was no significant effect of multiple platelet donations on Plt, PDW, MPV, P-LCR and MAR in blood donors. Plt has the most significant impact on MAR among platelet indexes of platelet donors.

Abstract: Objective　To analyze the clinical characteristics of children with lobar pneumonia and the distribution of pathogens in bronchoalveolar lavage fluid (BALF) collected from these patients, hence providing a scientific basis for their precise diagnosis and treatment. Methods　A total of 115 children diagnosed with lobar pneumonia from August 2019 to August 2022 at Suining Central Hospital were screened as the research subjects. The clinical manifestations and occurrence of complications in the patients were investigated. All the children underwent bronchoalveolar lavage after admission, and BALF samples were collected. Fluorescence quantitative PCR was adopted to detect and analyze the distribution and clinical characteristics of Streptococcus pneumoniae (SP) and other related pathogenic microorganisms in BALF specimens. Results Among the 115 pediatric patients with lobar pneumonia, the occurrence of manifestations or complications including involvement of ≥2 lung lobes, myocardial damage, pleural effusion, abnormal liver function, digestive system involvement, nervous system involvement, rash, renal function impairment, and lung atelectasis were observed in 46, 46, 39, 33, 18, 17, 11, 5, and 4 cases, respectively. The pathogen positivity rate in the BALF samples of the 115 patients was 87.0% (100/115), with 81 cases of single infection and 19 cases of mixed infection. A total of 121 strains of pathogens were isolated, including 83 strains of Mycoplasmal pneumonia (MP) (accounting for 68.6%) and SP(13.2%). The differences in the detection rates of HI, MP, RSV strains among different age groups were statistically significant (χ2=8.834, 19.454, 10.284, P<0.05), while the differences in the infection rates of SP, KP, CP, and ADV were not statistically significant (χ2=3.393, 2.67, 0.565, 0.097, P>0.05). The MP pneumonia group showed significantly higher incidence of complications such as pleural effusion, nervous system involvement, and abnormal liver function than the non-MP pneumonia group (χ2=3.925, 4.195, and 4.513, P<0.05). The highest pathogen detection rate was in winter, accounting for 33.91%. Conclusions MP is the most common pathogen in BALF of children with lobar pneumonia. There is variation in the pathogen detection rate among different age groups and seasons. Those with combined infections were more prone to complications, which is worthy of attention by clinicians.

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca²⁺ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
Mice ; Animals ; Reproducibility of Results ; Neurons ; Sensation ; Perception