Objective:To evaluate the clinical value of a capillary electrophoresis-based method for gene diagnosis of hyperphenylalaninemia.Methods:In this single-center prospective study, 40 newborns with suspected hyperphenylalaninemia detected by neonatal liquid chromatography-tandem mass spectrometry screening at Nanjing Maternity and Child Health Care Hospital from February 2021 to February 2023 were included, with 22 males, 18 females and a mean age at diagnosis of 21.93 days.Capillary electrophoresis was used to detect 85 variants of the phenylalanine hydroxylase ( PAH) gene in 40 newborns with suspected hyperphenylalaninemia.The PAH gene of undiagnosed patients was further analyzed by Sanger sequencing.The detection rate, sensitivity and specificity of capillary electrophoresis were calculated. Results:Among these 40 newborns with suspected hyperphenylalaninemia, 71 PAH variants were detected by capillary electrophoresis, 32 patients were clearly diagnosed, only 1 pathogenic variant was found in 5 patients, and no pathogenic variant was found in the last 3 patients.Therefore, the detection rate, sensitivity and specificity of capillary electrophoresis for analysis of the PAH gene were 80.00%, 88.75% and 100%, respectively. Conclusions:The capillary electrophoresis-based method can rapidly, efficiently and accurately detect PAH gene variants at lower cost and is a promising gene detection method for hyperphenylalaninemia in clinical practice.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

Objective:By investigating the awareness situation of scientific research integrity among scientific researchers,their behavior and attitudes towards scientific research integrity,and the reasons for the occurrence of scientific research integrity,to identify the key influencing factors and risk points,and propose targeted management ideas for scientific research integrity construction.Methods:A web-based questionnaire was used to survey the awareness of scientific research integrity policies,behavior and attitude,and reasons for dishonest behavior in scientific research among scientific researchers at a tertiary A hospital.Results:A total of 1,385 questionnaires were recovered,with 1,253 valid questionnaires.There were 246 males and 1,007 females,aged between 20 and 60 years old,with an average age of(37.98±8.97)years old.The average awareness rate of policies related to scientific research integrity was 39.44%.Scientific researchers believe that the top three risk points for dishonest behavior in scientific research were paper submission,entrusting third-party services,and the use of research funds.According to the different scientific research work involved by different survey subjects,the respondent population was set up with the attributes of the personnel in the basic information of the survey content on attitudes toward violating scientific research behavior norms,and was divided into four groups.The awareness situation of scientific research integrity policies was negatively correlated with the attitudes towards dishonest behavior in scientific research in the first and third groups.Publication of SCI papers and the awareness situation of scientific research integrity policies were negatively correlated with attitudes towards dishonest behavior in scientific research in the second group.Age and publication of SCI papers were related to attitudes towards dishonest behavior in scientific research in the fourth group,which were negatively correlated with the publication of SCI papers and positively correlated with age.Conclusion:The learning and training,and the rate of policy awareness of scientific research integrity were not high,and the awareness of scientific research integrity policies should be further improved.There are still risks and problems in the key links of scientific research activities,and it is necessary to strengthen the integrity management of the whole process of scientific research activities,establish the correct scientific values of scientific researchers,improve the scientific research evaluation system,and create a good scientific research environment.

Objective:To explore the current status and correlation of occupational stress and burnout among pediatric nurses.Methods:From April 2023 to January 2024, convenience sampling was used to select 150 pediatric nurses from Taizhou Hospital of Zhejiang Province, East Campus of Taizhou Hospital of Zhejiang Province, and Taizhou Enze Medical Center as research subjects. The survey was conducted using the General Information Questionnaire, Chinese version of the Maslach Burnout Inventory General Survey, and Nurse Job Stressors Scale.Results:A total of 150 nurses were surveyed, and 149 valid questionnaires were collected, with a valid response rate of 99.33%. Pediatric nurses had high scores in emotional exhaustion and depersonalization dimensions in occupational burnout. The job stressors for pediatric nurses were ranked in order of their scores in each dimension, including workload and time management, work environment and resources, nursing profession and work, management and interpersonal relationships, and patient nursing. There were correlations between occupational burnout and occupational stress among pediatric nurses in multiple dimensions (all P<0.05) . Conclusions:Pediatric nurses have a relatively high level of occupational burnout and often face significant occupational stress. In the development of the healthcare system, attention should be paid to the occupational burnout and stress of pediatric nurses. The physical and mental health of pediatric nursing staff can be promoted and work efficiency can be improved by reducing the overloaded work of pediatric nurses, optimizing personnel allocation, and improving social support.

Purpose To investigate the value of 99Tcm-(methoxyisobutvlisonitrile,MIBI)bone uptake on hungry bone syndrome(HBS)in renal secondary hyperparathyroidism(SHPT)after parathyroidectomy.Materials and Methods From June 2014 to December 2021,106 renal SHPT patients who underwent successful parathyroidectomy in Jiangyin Hospital Affiliated Nantong University were retrospectively enrolled.Visual analysis was used to evaluate the abnormal bone uptake of 99Tcm-MIBI.The patients were divided into HBS group and non-HBS group based on whether occurred HBS.The clinical features,laboratory indicators and 99Tcm-MIBI bone uptake were compared between the two groups.Results Of 106 renal SHPT patients,42(39.62%)patients with bone uptake on visual assessment,showed diffusely increased tracer accumulation,particularly in sternum,clavicle and ribs.The age in HBS group was younger than that in non-HBS group(t=-3.058),the alkaline phosphatase and parathyroid hormone level in HBS group were higher than that in non-HBS group(Z=-5.148,-2.218),the serum corrected calcium in HBS group was lower than that in non-HBS group(Z=-2.102),the positive rate and number of 99Tcm-MIBI bone uptake in HBS group was 50%and 2(1,3),which was higher than that of 28%and 1(1,1)in non-HBS group(χ2=5.344,Z=-2.970),respectively,all showed statistically significant difference(all P<0.05).Conclusion Renal SHPT patient with HBS after parathyroidectomy is commonly related to a high level of alkaline phosphatase and parathyroid hormone,and more likely to develop abnormal 99Tcm-MIBI bone uptake.

Helicobacter pylori (H. pylori) neutrophil-activating protein (HP-NAP) is one of the newly discovered main virulence factors of H. pylori, and is expressed in almost all strains of H. pylori. After being activated, HP-NAP can participate in the development of inflammation and tissue damage by stimulating neutrophils, monocytes, dendritic cells, mast cells and lymphocytes. This paper reviewed the latest research progress of HP-NAP in the prevention and treatment of related diseases.

Humans ; COVID-19 ; HIV Infections/drug therapy* ; Risk Factors

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Objective:To investigate the effect of aucubin on behaviors and excessive activation of astrocytic in attention deficit/hyperactivity disorder (ADHD) model mice.Methods:Twelve wild-type C57BL/6 pregnant mice (female, clean grade) were intraperitoneally administered with esketamine (15 mg/kg) to establish an ADHD model in offspring mice. The offspring mice were divided into control+ saline group, control+ aucubin group, Ketamine+ saline group and Ketamine+ aucubin group according to the nest matching principle with 15 in each group.At 14 days after birth, mice in the control+ aucubin group and Ketamine+ aucubin group were administered with aucubin (5 mg/kg, once a day) by gavage for 5 days. Mice in control+ saline group and Ketamine+ saline group were administered with equal volume of 0.9% sodium chloride solution. The offspring mice were housed with their mothers in the same cage until 21 days after birth. Twenty-one days after birth, the offspring mice were evaluated by open field test and elevated plus maze tests. Immunofluorescence assay was used to detect the expression of glutamate decarboxylase 2 (GAD2), γ- aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) in the amygdala. The morphological changes of astrocytes were quantitatively analyzed by Sholl analysis. GraphPad Prim 9.0.1 software was used for statistical analysis. The comparison of multiple groups was conducted by one-way ANOVA or Kruskal-Wallis test.Results:(1)The results of behavioral experiments showed that the total distance traveled in the open field test and the residence time in open arm of the elevated plus maze were statistically significant ( F=236.90, H=39.92, both P<0.001). The total distance ((7 044±249)mm, (22 891±2 175)mm, P<0.05) and the residence time in open arm(12.69(9.86, 17.24)s, 2.72(0.57, 3.87)s, P<0.05) of mice in Ketamine+ saline group were both higher than those in control+ saline group.The total distance((22 891±2 175)mm, (8 252±839)mm, P<0.05) and the the residence time in open arm(5.45(1.13, 10.99)s, 12.69(9.86, 17.24)s, P<0.05) of Ketamine+ aucubin group were both lower than those of Ketamine+ saline group.(2)The immunofluorescence results showed that the levels of GAD2, GABA and GFAP intensity in amygdala of mice in the four groups were statistically significant ( F=145.50, 50.08, 53.83, all P<0.05). Compared with control+ saline group, the fluorescence intensities of GAD2 ((100.00±9.60)%, (24.86±4.14)%, P<0.05) and GABA ((100.00±16.84))%, (25.48±5.70)%, P<0.05) of Ketamine+ saline group were down-regulated, and the GFAP((100.00±18.02)%, (223.80±25.85)%, P<0.05) was up-regulated. Compared with Ketamine+ saline group, the fluorescence intensities of GAD2 ((24.86±4.14)%, (56.08±6.55)%, P<0.05) and GABA((25.48±5.70)%, (52.59±15.74)%, P<0.05) in Ketamine+ aucubin group were up-regulated, but the fluorescence intensity of GFAP ((223.80±25.85)%, (157.10±22.10)%, P<0.05) was down-regulated.(3)Sholl analysis indicated that the number of the intersections between the astrocyte processes or the branches of astrocyte processes was statistically significant in the 4 groups ( F=12.47, P<0.05). Compared with control+ saline group, the number of the intersections in Ketamine+ saline group((2.07±0.48), (1.67±0.72), P<0.05) increased. While the number of the intersections in Ketamine+ aucubin group was lower than that of Ketamine+ saline group ((1.20±0.78), (2.07±0.48), P<0.05). Conclusion:Aucubin administration can alleviate ADHD-like behaviors in offspring mice, and the mechanism may be associated with the inhibition of excessive astrocytic activation.

Objective:To explore the views of general practitioners (GPs) on developing special interests in the context of the county medical community.Methods:A survey was conducted using self-designed questionnaire from November and December 2019, among 49 general practice residents trained in the First Affiliated Hospital of Zhejiang University School of Medicine. Meanwhile, structured interviews were undertaken with 14 general practice residents.Results:Forty-nine valid questionnaires were collected with a response rate of 100.0%. All participants were from the county medical community units. The survey showed that 91.8% (45/49) of respondents were willing to develop special interests and 79.6% (39/45) chose one subject, and the top three subjects were endocrinology, gastroenterology and cardiology. The structured interviews demonstrated that most participants did not understand meaning of general practitioners with special interests (GPwSIs) clearly and were unable to distinguish GPwSIs from specialists; they were confused about the status, training mode, and assessment standards of GPwSIs. The interviews also showed that the demand for developing special interests for them was derived from the needs of patients for diagnosis and treatment, the target population of health care services, peer advice and personal interests.Conclusions:Most general practice residents are willing to develop special interests, and internal medicine is the first choice; however, their understanding of the GPwSIs is insufficient. The survey suggests that the position, training model, assessment and certification of GPwSI need to be further clarified.