ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

The purpose of this study was to understand the prevalence of Neoehrlichia mikurensis in rodents in Yunnan commensal rodent plague foci.Lianghe Country,Mangshi City,and Mile City in Yunnan Province were chosen as sampling sites,where rodents were captured with dead-traps.The N.mikurensis groEL gene in rodent spleen samples was detected with nested PCR,and the positive products were sequenced with Sanger bidirectional assays.The infection rate of N.mikurensis a-mong plague foci,habitats,species,and sexes was compared with Chi-square tests or Fisher's exact probability method.Of 656 rodent spleen samples,12 N.mikurensis positive samples were detected in R.tanezumi,R.sladeni,N.confucianus,and B.bowersi.The positivity rate was 1.83％.No significant difference in the N.mikurensis positivity rate was observed a-mong plague foci,habitats,species,and sexes(P＞0.05).Genetic evolution analysis of the groEL gene indicated that the se-quence similarity of nucleic acid sequences in 12 positive samples was 99.5％-100％,and the nucleic acid sequences of N.mikurensis were in the same branch,belonging to cluster Ⅳ.Thus,four species of rodents were found to have low frequency infection with N.mikurensis in Yunnan commensal rodent plague foci.

This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

Objective:To develop a task-oriented exercise(TOE)program suitable for hospitalized elderly frailty patients, and to evaluate its effects on patients' upper and lower limb mobility and activities of daily living.Methods:Using the convenience sampling method, 60 elderly frailty patients admitted to Beijing Hospital between August and December 2019 were selected and randomly divided into a TOE group and a conventional care group, with 30 in each group.In addition to conventional treatment and care, the TOE group performed task-oriented training(turning to fetch objects and multidirectional stepping), while the conventional care group performed aerobic training and resistance training.Both groups completed 10 training sessions.Baseline data of patients in both groups were assessed before intervention.Grip strength(as a measure of upper limb motor function), the motor component of the World Health Organization disability assessment schedule(WHODAS)2.0(as a measure of lower limb motor function), and the modified Barthel index(as measure of the ability to perform activities of daily living)were assessed after intervention.Results:Before intervention, the grip strength values of the TOE group and the conventional care group were(20.21±6.39)kg and(17.61±10.59)kg, and the scores of the motor component of WHODAS 2.0 were(16.07±6.64)and(20.23±1.18), respectively.After intervention, the grip strength value and the score of the motor component of WHODAS 2.0 of the TOE group were(22.13±5.97)kg and(12.86±5.17)kg, respectively, with statistically significant differences compared with those of the conventional care group, which were(19.05±9.16)kg for grip strength and(15.67±1.11)for the motor component of WHODAS 2.0( t=2.005, P=0.049; t=-18.210, P<0.001).The value of grip strength and the score of the motor component of WHODAS 2.0 were higher post-intervention than pre-intervention in the TOE group( t=5.005、-5.291, P<0.001 for both), but they showed no statistical differences in the conventional care group( t=0.247、1.614, P=0.806, 0.112).After intervention, the total modified Barthel index scores of the TOE and conventional care groups were (55.27±37.12)and(57.27±33.39), respectively, higher than the pre-intervention scores, which were(42.27±29.92)and(40.54±20.55), respectively(both P<0.05).There was no statistical difference in total Barthel score between the two groups after intervention( t=1.042, P=0.303). Conclusions:For hospitalized elderly frailty patients, the TOE program is simple, easy to implement, safe and effective, and can not only achieve the same purpose of improving the ability to perform activities of daily living as the conventional exercise program, but also improve the performance of upper and lower limb motor function more quickly.

Objective:To investigate the genetic causes in a phenotypically normal couple with three pregnancies of trisomy 21 offspring.Methods:A retrospective analysis was conducted on a phenotypically normal couple who had three pregnancies with trisomy 21 syndrome offspring and were transferred to Shandong Provincial Maternal and Child Health Care Hospital in December 2023. Genetic analysis was performed using quantitative fluorescence polymerase chain reaction (QF-PCR), karyotype analysis, chromosome microarray analysis (CMA), and fluorescence in situ hybridization (FISH). Relevant articles up to December 31, 2023, were retrieved from CNKI, Wanfang Database, Yiigle, and VIP using the terms "recurrent pregnancy", "consecutive pregnancy", "two pregnancies", and "trisomy 21 syndrome (Down syndrome)" in Chinese. Additionally, the English terms "recurrence or recurrent" "trisomy 21 syndrome" and "Down syndrome" were used to retrieve articles from PubMed, Embase, and Web of Science. The genetic causes of recurrent pregnancies with trisomy 21 syndrome fetuses were analyzed and summarized. Results:(1) Case from this hospital: Results of QF-PCR, karyotype analysis, and CMA of amniotic fluid cells in this pregnancy all indicated that the fetus had trisomy 21 syndrome. FISH tests on oral mucosal cells, decidual tissue, and urine sediment cells of the pregnant woman all indicated that she was a mosaic for trisomy 21. Additionally, QF-PCR detection of short tandem repeat (STR) loci on chromosome 21 suggested that there might be gonad mosaicism in the pregnant women, and an extra chromosome 21 in the fetus was derived from gonad mosaicism 21 trisomic cells. (2) Literature review: A total of 13 case reports with detailed records of recurrent pregnancy trisomy 21 syndrome history and related test results of both partners were retrieved, making a total of 14 cases, including seven cases each with a history of 2 and 3 trisomy 21 pregnancies. Translocation trisomy 21 was detected in each pregnancy of two cases. Of the 14 cases, five cases were only detected by peripheral blood samples of the couple, and the results were normal. The other nine cases were also detected by skin fibroblasts (six cases), ovarian tissue cells (two cases), oral mucosa cells (two cases), semen (two cases), and urinary sediment cells (one case), among which six cases indicated that one of the parents was chimeric trisomy 21, and five cases were female chimerism, one case was male chimerism. Only two cases were found to have mosaic trisomy 21 in peripheral blood sample, and the chimerism ratio was lower than that of other samples detected at the same time. In five cases, the extra chromosome 21 was found to be of maternal origin through testing of STR loci on chromosome 21.Conclusions:Parental mosaicism is an important cause of recurrent pregnancies with trisomy 21 syndrome. Testing samples from skin, oral mucosa, blood, semen, and ovaries can help detect low-level mosaicism.

Objective To study the changes of volume and cognitive function in hypothalamic subregions based on automated MRI segmentation at various stages of adult life and the correlation between them.Methods Totally 314 healthy subjects aged 20-89 years old were selected from the public database of Dallas Lifespan Brain Study(DLBS),and then divided into a youth group(20-35 years old),an early-middle age group(36-50 years old),a late-middle age group(51-65 years old)and an elderly age group(66-89 years old).The structural magnetic resonance imaging(sMRI)images of the 314 subjects were treated with Freesurfer software to determine the volumes of the anterosuperior,anterior-inferior,middle-superior,middle-inferior and posterior subregions of the right and left sides of the hypothalamus.Differences in hypothalamic subregion volumes between the 4 groups were compared using analysis of covariance,and multiple comparisons between the 4 groups were performed using Bonferroni correction.Pearson's correlation coefficients were used to analyze the correlations of the hypothalamic subregion volumes with the scores of mini mental state examination(MMSE),digit comparison(DC)test,digit symbol(DS)test,and Hopkins verbal learning test(HVLT).Results The volumes of all the hypothalamic subregions except the right anterior inferior part decreased significantly with age(P＜0.05).All the hypothalamic subregions except the right anterior inferior part had the volumes correlated with MMSE scores positively(P＜0.05);the DC test scores were correlated positively with all the hypothalamic subregion volumes(P＜0.05);the DS test scores were correlated positively with the volumes of the hypothalamic subregions except the bilateral anterior-inferior part(P＜0.05);the scores of HVLT immediate memory test were positively correlated with the anterior-superior,middle-superior and posterior subregion volumes of the right and left sides of the hypothalamus(P＜0.05);the scores of HVLT delayed memory test were correlated positively with the volumes of the bilat-eral anterior-superior and left-middle-superior subregions(P＜0.05);the scores of HVLT delayed recognition test did not cor-relate with all the hypothalamic subregions(P＞0.05);the volumes of the bilateral hypothalamus were positively correlated with the scores of MMSE,DC test,DS test and HVLT immediate memory test(P＜0.05).Conclusion Volume changes in some hy-pothalamic subregions are associated with age-related memory decline during adult aging,which can be used to assess the risk of memory loss throughout adulthood.[Chinese Medical Equipment Journal,2024,45(5):8-15]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder(PTSD)rats.Methods Thirty male SD rats were used to construct a rat model of single prolonged stress(SPS).The model rats were randomly divided into the SPS,icariin,and icariin + K252a(tyrosine kinase receptor B inhibitor)groups(n= 10 each;another 10 normal rats were used as the control group).The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS,while the control and SPS groups were administered the same dose of normal saline.K252a cells were injected into the lateral ventricles.After 2 weeks,anxiety,depression,and fear memory disorder in rats in each group were detected by the mine experiment,ele-vated cross maze experiment,and conditional fear test.The binding activity of icariin to brain-derived neurotrophic factor(BDNF)and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry.The relative expressions of BDNF and TrkB pro-teins were detected by Western blotting.The expressions of postsynaptic density protein 95(PSD95)and synaptophysin(SYN)in the rat amygdala were detected using immunofluorescence.Results Icariin showed strong binding to BDNF.Compared with the control group,the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced.The open arm entry(OE)and arm opening time(OT)were significantly reduced,the freezing time and defecation times were significantly increased,and the expressions of the BDNF,TrkB,PSD95,and SYN proteins were significantly reduced(P<0.05).Compared with the SPS group,the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area,significantly increased OE and OT,significantly reduced the time of immobilization and defecation,and significantly increased the expressions of BDNF,TrkB,PSD95,and SYN proteins(P<0.05).Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats.This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.