ObjectiveTo explore the possible mechanism of Pingwei Capsules （平胃胶囊） for chronic atrophic gastritis from rapidly accelerated fibrosarcoma / mitogen-activated protein kinase /extracellular-signal-regulated kinase （Raf/MEK/ERK） pathway that influences the activation of fibrosarcoma protein/mitogen. MethodsFifteen SD rats were randomly divided into 5 rats in the blank group and 10 rats in Pingwei Capsules group. The rats in the blank group were given 1 ml/100 g of saline by gavage， and the rats in Pingwei Capsules group were given 0.63 g/（kg·d） of Pingwei Capsule suspension by gavage， and serum was collected for 3 consecutive days. N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was used to induce human gastric mucosal epithelial cells GES-1 to establish a precancerous lesion cell model. The successful cells were divided into control group （10% fetal bovine serum）， blank serum group （10% fetal bovine serum plus 10% blank serum）， and medication-containing serum group （serum with medication of Pingwei Capsule）， and the volume fraction and time of intervention of Pingwei Capsule-containing serum were screened by CCK-8 assay. Human gastric mucosal epithelial cells GES-1 were divided into normal group， model group， blank serum group， medication-containing serum group， U0126 group， and combined group， with 6 replicate wells in each group. After successful modelling of the cells in all groups except the blank group， an equal volume of fetal bovine serum was added to the normal and model groups， an equal volume of blank serum was added to the blank serum group， a screening volume fraction of Pingwei Capsule-containing serum was added to Pingwei Capsule group， a 10 μmol/L mitogen-activated extracellular signal regulated kinase 1 （MEK1） inhibitor U0126 was administered in the U0126 group， an equal dose of Pingwei Capsule-containing serum plus 10 μmol/L of U0126 was administered to the combined group. After the selected incubation time， the level of interleukin 6 （IL-6） was detected in the cells by ELISA， the expression of IL-6 and MEK1 was detected by immunofluorescence， and the expression of IL-6， Raf， MEK1， and ERK mRNA was detected by RT-qPCR， and the expression of IL-6， Raf， MEK1， and ERK mRNA in the cells was detected by Western blot. ResultsThe 5.35% volume fraction， 48 h intervention of Pingwei Capsule-containing serum was selected for subsequent experiments. Compared with the normal group， the IL-6 content in cell supernatants and the expression of IL-6， Raf， MEK1， ERK mRNA and ERK1/2 proteins in cells increased in the model group and blank serum group （P＜0.01）. Compared with the model group， all of the above indexes were improved in medication-containing serum group， U0126 group， and combined group （P＜0.05 or P＜0.01）. Compared with medication-containing serum group， the expression of IL-6， MEK1 expression， the expression of IL-6， Raf， MEK1 and ERK mRNA， and the expression of IL-6， Raf， MEK1 and ERK1/2 proteins reduced in the cells of combined group （P＜0.05 or P＜0.01）. Compared with the U0126 group， IL-6 expression reduced and IL-6， MEK1 and ERK1/2 protein expression reduced in cells of combined group （P＜0.05 or P＜0.01）. ConclusionThe Pingwei Capsule-containing serum may play a role in the treatment of chronic atrophic gastritis by improving the inflammation-cancer transformation of GES-1 cells through inhibiting the Raf/MEK/ERK pathway.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective:To investigate the level of functional fitness of elderly hypertensive patients in the community and to analyze its influencing factors.Methods:A cross-sectional survey was used from November 2021 to September 2022, questionnaire survey and Senior Functional Fitness Test (SFT) were conducted on 189 elderly hypertensive patients in the community by convenience sampling method, multiple linear regression was used to analyze the influencing factors of SFT in elderly hypertensive patients in the community.Results:Totally 189 cases of community-aged hypertensive patients completed the investigation, 88 cases were male and 101 were female. The total SFT score of community-aged hypertensive patients was (58.61 ± 16.07). Single factor analysis showed that there were significant differences in SFT scores among patients with different gender, age and education ( t=-2.57, F=6.24, 7.54, all P<0.05). Multifactorial analysis revealed that age ( t=-5.55), gender ( t=2.63), and literacy ( t=5.69) were influential factors in the total SFT scores of community-dwelling elderly hypertensive patients (all P<0.05). Conclusions:Age, gender, and literacy level are the main factors affecting the total SFT scores of elderly hypertensive patients in the community, and community caregivers should pay close attention to the above elderly hypertensive population.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To investigate the application of patient-based real-time quality control (PBRTQC) using exponentially weighted moving average (EWMA) method in internal quality control (IQC) procedures of thyroid function tests.Methods:The serum thyroid function test results of outpatients and inpatients in the Second Hospital of Shandong University from December 1, 2022 to April 30, 2023 were collected. Based on the PBRTQC professional intelligent software system, normality correction, parameter setting, program preparation and real-time operation of test data were carried out. The results of all patients who underwent thyroid function testing between May 1, 2023 and August 31, 2023 were used as the validation dataset. The estimated EWMA value of thyroid function test results and the cumulative coefficient of variation ( CV) over 4 months were calculated. The cumulative CV was compared with the criteria of precision quality standard (1/3TEa) and the CV of IQC. Westgard 2-2s and 1-3s rules were used for alarm setting. The early warning information of the EWMA quality control program were recorded and the potential causes of performance changes were analyzed. DxLab Mind software was used to conduct normal distribution statistics for all data, and the Kolmogorov-Smirnov test was performed on the test results. Results:The items related to serum thyroid function of the patients were all positively skewed. After data correction by Box-Cox method, the PBRTQC data of free triiodothyronine (FT3) and free thyroxine (FT4) were normally distributed, and their cumulative precisions ( CV) of EWMA within 4 months were 6.26% and 2.86%, respectively, both of which were lower than the precision quality target of 8.33%. However, the data of thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TgAb) were still positive skewed after modification. The EWMA cumulative CV of TSH, TPOAb and TgAb were 13.16%, 15.31% and 16.77%, which were higher than the precision quality targets of 8.33%, 10% and 10%, respectively. The EWMA QC program can detect different out-of-control alarms, including FT4 false alarms due to sample source concentration and TSH result bias caused by changes in reagent performance. In addition, the EWMA QC program can also detect differences in FT3 results between different DXI800 fully automated chemiluminescence instrument instruments. Conclusions:The EWMA program based on PBRTQC professional intelligent software tools can monitor the patient data of the detection system in real time and continuously, dynamically identify and monitor the errors generated during the analysis process and give early warning. It can be used as a useful supplement for the daily IQC of thyroid function items, especially FT3 and FT4, and has good clinical application value.

ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang （CLMT） on rat depression model prepared by chronic unpredictable mild stress （CUMS） based on cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）-brain-derived neurotrophic factor （BDNF） signaling pathway. MethodSixty SD rats were divided into normal group， model group， and CLMT low-， medium- and high-dose groups and fluoxetine group （positive control） according to random number table. They， except the normal group， were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-， medium- and high-dose groups were given 2.89， 5.78 11.56 g·kg^-1 of CHMD granules， respectively， and the fluoxetine group was given 2.06 mg·kg^-1 of fluoxetine hydrochloride on the 29^th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE） and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of PKA， CREB， and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB， and hematoxylin and eosin （HE） staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group， the immobility time of the model group in the forced swim test was increased （P<0.01） and the total movement distance， residence time in central area， number of entries in central area and movement distance in central area were decreased （P<0.01）. Additionally， the contents of 5-HT， NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA， BDNF and CRE，the mRNA expressions of BDNF and CREB were lower than those in the normal group （P<0.01）. Compared with the model group， the CLMT groups had reduced immobility time （P<0.01）， elevated total movement distance， residence time in central area， number of entries in central area and movement distance in central area （P<0.05， P<0.01）， up-regulated contents of 5-HT， NE and cAMP in hippocampus （P<0.05， P<0.01）， and up-regulated protein expressions of PKA， BDNF and CREB and mRNA expressions of BDNF and CREB （P<0.01）. HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats， activating cAMP/PKA/CREB/BDNF signaling pathway， up-regulating the expression of BDNF and protecting hippocampal structure and function .

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Child ; Child, Preschool ; Humans ; Male ; Cafe-au-Lait Spots ; Computational Biology ; Genetic Testing ; Genomics ; Intellectual Disability/genetics* ; Mutation

ObjectiveTo investigate the monitoring status and epidemiological characteristics of foodborne disease pathogens in Baoshan District， Shanghai so as to improve early detection and warning capabilities of foodborne diseases outbreaks， and to provide a scientific basis for the prevention and control of foodborne diseases. MethodsAnal swabs or fecal samples from food-borne diarrhea cases were collected from two sentinel surveillance medical institutions in Baoshan District of Shanghai during 2019 and 2021. Salmonella， diarrheagenic Escherichia coli， Shigella， Vibrio parahaemolyticus， campylobacter and norovirus were tested in anal swabs and fecal samples， and all the testing results were statistically analyzed. ResultsA total of 1 693 cases were reported， among which 1 693 anal swabs and fecal samples were collected， with a male-to-female ratio of 1.04∶1. The largest number of cases was from the age group of 45-64 years （504 cases）. The highest number of reported cases was among retirees （762 cases）. The high-incidence period of the diseases was in summer and autumn， with the highest number of cases associated with meat and meat products （566 cases）. The primary location of exposure was at home （1 260 cases）. The detection rate of pathogenic bacteria and virus was 21.32%， among which campylobacter accounted for the largest proportion （10.28%）. The peak incidence rate was from May to September. The detection rate of norovirus was 13.29%， with a higher incidence in winter and spring. The predominant serotype of Salmonella was Salmonella enteritidis （41.82%）， and the predominant local serotype of diarrheagenic Escherichia coli was EAEC （50.52%）. Campylobacter was mainly represented by jejuni （81.61%）， and the predominant type of norovirus was GⅡ （60.87%）. ConclusionCampylobacter has the highest proportion among foodborne pathogens causing foodborne diseases in Baoshan District， followed by diarrheogenic Escherichia coli. And norovirus GⅡ type is the predominant virus. Appropriate prevention and control measures should be taken based on the characteristics of each pathogen's epidemiology.

Objective: To measure the body mass index (BMI) of secondary school students and analyze its association with the physical fitness index, so as to improve the physical health of middle school students. Methods: Using a randomized cluster stratified sampling method, 3 813 secondary school students from six cities (Ganzhou, Ji an, Fuzhou, Nanchang, Shangrao and Jiujiang) in Jiangxi Province, China, were selected in September 2022. Questionnaire survey was administered to obtain basic information and to assess the nutritional status and physical fitness tests were conducted among secondary school students. The study was stratified by gender and age, and the Kruskal Wallis H test was used to compare the differences in the mean values of grip strength, sit-ups, standing long jump performance and strength quality among secondary school students with different BMI levels, while the correlation between BMI and strength quality index was inferred by using curve regression analysis. Results: There was statistical significance in the strength quality index of middle school students with different BMI level ( H=56.79, 8.84, P <0.05). Except 13 years old group, the difference of physical fitness by BMI grade strength quality index of boys in other age groups was statistically significant ( H =22.21, 16.23, 17.98, 18.21, 8.08), while the difference of physical fitness by BMI of girls at 14 years old was statistically significant ( H =9.11)( P <0.05). The curve fitting using regression showed that the physical fitness index and BMI of middle school students (boys and girls) show an inverted U-shaped curve. The physical fitness index was higher in the middle region of BMI ( Z-score) and lower in the two end regions, while showing a decreasing trend from the middle to the two ends. Conclusion An association is found between BMI and physical fitness among secondary school students in Jiangxi Province, and wasting and overweight/obesity are negatively correlated with physical fitness. Greater attention should be paid to the nutritional status of secondary school students to ensure the normal development of physical fitness.