ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate （ATP） binding cassette transporter G2 （ABCG2） expression in hyperuricemic （HUA） rats， and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley （SD） rats were randomized into a normal group， a model group， low-dose （282.6 mg·kg^-1） and high-dose （565.2 mg·kg^-1） Simiaowan groups， and a Benzbromarone （4.7 mg·kg^-1） group. The HUA model was established via intraperitoneal injection of potassium oxonate （ip） combined with oral gavage of hypoxanthine （ig） for 14 days. Following modeling， treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin （HE） staining， and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay （ELISA） quantified tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， diamine oxidase （DAO）， and D-lactic acid （D-LA） levels. Real-time polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry assessed the expression of Claudin-1， Occludin， occludens-1 （ZO-1）， and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group， the model group exhibited epithelial shedding in the ileal villus， structural disruption， infiltration of extensive inflammatory cells， and significantly elevated Chiu's scores （P<0.01）. The DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum were markedly increased （P<0.01）， while mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion， were significantly reduced （P<0.01）. Compared with the model group， the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus， significantly lowered Chiu's scores （P<0.01）， significantly reduced DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum （P<0.01）， and upregulated mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion （P<0.01）. The 16S rDNA results showed that in the model group， the α-diversity index of the ileal microbiota was increased， and species diversity and richness were enhanced， with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased， and the abundance of pathogenic bacteria was increased， with butyrate-producing bacteria showing a low abundance. In contrast， Simiaowan at all doses reduced species diversity and richness， regulated microbiota dysfunction， and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria， decreased the abundance of harmful bacteria， and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Objective:To investigate the nutritional risk status of children in PICU and analyze its influencing factors.Methods:From July 2021 to February 2023,all children aged 1 to 18 years admitted to PICU of Beijing Children's Hospital were investigated by using the pediatric Yorkhill Malnutrition Scoring tool(PYMS)and the clinical data questionnaire.Results:A total of 492 children in PICU were enrolled.The first nutritional risk screening results showed that there were 32 cases of no/low nutritional risk(6.5%),76 cases of medium risk(15.4%),and 384 cases of high risk(78.1%).The incidence of medium/high nutritional risk was as high as 93.5%.The PYMS score of nutritional risk in PICU was(2.61±1.42).The results of multiple linear regression analysis showed that weight,fever time before admission,white blood cells,body mass index,primary diagnosis,father's education,and diet before illness were the main influencing factors of nutritional risk of children in PICU(P<0.05).Conclusion:Children in PICU are in a state of high nutritional risk.It is suggested that children in PICU should carry out nutritional screening in a standardized manner,identify children with high nutritional risk and its influencing factors early.To actively conduct nutritional assessment and nutritional intervention could improve the clinical outcome of children in PICU.

Objective To investigate the clinical characteristics in an elderly patient with sellar multiple myeloma.Methods Clinical features,laboratory data and radiologic profile of an elderly patient with sellar multiple myeloma were collected.Results The patient was an 85-year-old male.The main clinical manifestations were fatigue,poor appetite and polyuria.Laboratory examinations showed a significant decrease in blood sodium,several anterior pitu-itary hormones and an increase in total protein,mass of pituitary lesion and concentration of prolactin.During etio-logical screening,it was found that the blood immunoglobulin G(IgG)level was significantly increased,the blood M protein was positive and the bone marrow smear showed myeloma cells accompanied by multiple osteolytic lesions in the bones of the whole body.Considering the diagnosis of multiple myeloma,the pituitary lesion was likely to be the extra-medullary involvement.Conclusions The intrasellar plasmacytoma is not common.The disease onset is insidious with clinical features and imaging findings lacking specificity.Therefore,diagnosis relies on biopsy which poses risks for elderly patients and increases diagnostic challenges leading to misdiagnosis.

Objective To evaluate the application of flipped classroom(FC)approach in endocrine system integrated course for students from 4+4 clinical medicine pilot class at Peking Union Medical College(PUMC).Methods The study included the students of 4+4 clinical medicine pilot class grades 2019-2023 in PUMC.The students of grades 2019-2021(n=77)served as the control receiving traditional teaching method,while the students of grades 2022 and 2023(n=76)were selected as the experimental group,which were taught by FC approach.The selected teaching content is thyroid theme.The scoring rates of thyroid related questions in the final exam were as-sessed and a questionnaire survey was conducted to evaluate teaching satisfaction and effectiveness.Results The scoring rates of experimental group were significantly higher as compared to that of control group(P＜0.05).Over 90％of the students in the experimental group strongly satisfied or satisfied with the teaching content arrangement,design form,classroom atmosphere,teacher-student interaction of FC and expressed willingness to continue with this methodology.In addition,over 90％of the students strongly agreed or agreed that FC stimulated learning inter-est,improved self-learning ability,strengthened the connection between theory and clinical practice,inspired clini-cal reasoning,enhanced the abilities to analyze and solve problems,and cultivated communication and teamwork skills.Conclusions The application of FC approach in endocrine system integrated course achieved excellent teaching outcomes with high satisfaction of the students.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Objective To investigate the changes of serum sclerostin(SOST)and secreted frizzled related protein 5(SFRP5)levels and their prognostic value in patients with post-traumatic osteoarthritis(PTOA).Methods 84 patients with PTOA admitted to the hospital from January 2020 to January 2022 were selected as the disease group,and 84 healthy patients who underwent physical examination in the hospital during the same period were selected as the health group.Serum SOST and SFRP5 levels were detected in the diseased and healthy groups by enzyme-linked immunosorbent assay.The patients in the disease group were followed up for 1 year and the prognosis of PTOA patients was evaluated by Lysholm knee function score.Spearman correla-tion analysis was used to analyze the correlation between serum SOST,SFRP5 and Lysholm knee function score in PTOA patients.Multivariate Logistic regression was used to analyze the prognostic factors of PTOA patients.The predictive value of serum SOST and SFRP5 levels in poor prognosis of PTOA patients was ana-lyzed by receiver operating characteristic(ROC)curve.Results Compared with the healthy group,the serum SOST and SFRP5 levels in the disease group were significantly decreased,and the difference was statistically significant(P＜0.05).Spearman correlation analysis showed that serum SOST and SFRP5 levels were posi-tively correlated with Lysholm knee function score.Multivariate Logistic regression analysis showed that body mass index＞25 kg/m2,Kelgran-Lawrence grade Ⅲ/Ⅳ at admission and cartilage Outerbridge grade Ⅲ/Ⅳ at admission were independent risk factors for poor prognosis in PTOA patients(P＜0.05).Long-term exercise,SOST and SFRP5 levels were protective factors(P＜0.05).ROC curve analysis showed that the area under ROC curve(AUC)of serum SOST and SFRP5 combined in predicting poor prognosis of PTOA patients was higher than that of SOST and SFRP5 alone in predicting poor prognosis of PTOA patients(Z=2.316,P=0.021;Z=2.356,P=0.019).Conclusion Serum SOST and SFRP5 levels are reduced in PTOA patients compared to healthy individuals,both of which are associated with poor prognosis in PTOA patients and have some predictive efficacy for patient prognosis.

ObjectiveTo investigate the objective characteristics of tongue manifestations in patients with coronary heart disease （CHD）. MethodsA total of 315 participants with CHD were recruited in the CHD group， and 211 healthy participants who underwent physical examination were recruited as the healthy control group. In addition， according to the common comorbidities （primary hypertension， carotid atherosclerosis， type 2 diabetes mellitus， fatty liver， hyperlipidaemia， heart failure， and cerebral infarction） in 315 participants with CHD， each comorbidity was classified into a group of comorbidities with that disease and a group of non-comorbidities. Tongue images were captured using a TFDA-1 tongue diagnostic instrument to characterise the tongue body （TB） and tongue coating （TC）， comparing the RGB， HIS， and Lab colour spaces in the chromaticity index （R， red； G， green； B， blue； H， hue； I， intensity； S， saturation； L， lightness； a， red-green axis； b， yellow-blue axis）， the tongue coating thickness index （per-All）， contrast （CON）， angular second moment （ASM）， entropy （ENT）， and mean （MEAN） in texture metrics. ResultsCompared with the healthy control group， the characteristic indexes of tongue body in CHD group showed lower TB-R， TB-G， TB-B， TB-I， TB-L and higher TB-H， TB-b； and the characteristic indexes of tongue coating in CHD group showed lower TC-R， TC-B and higher TC-CON， TC-MEAN， TC-H， TC-b （P＜0.05 or P＜0.01）. Compared with non-combined primary hypertension group， CHD combined primary hypertension group showed higher per-All， TB-G， TB-L， and lower TB-a， TC-a （P＜0.05）； compared with the non-combined carotid atherosclerosis group， CHD combined carotid atherosclerosis group showed higher TB-CON， TB-ENT， TB-MEAN， and lower TB-ASM （P＜0.05 or P＜0.01）； compared with the non-combined type 2 diabetes mellitus group， CHD combined type 2 diabetes mellitus group showed lower per-All and higher TB-H （P＜0.05 or P＜0.01）； compared with the non-combined fatty liver group， CHD combined fatty liver group showed higher TB-CON， TB-MEAN， TB-ENT， and lower TB-ASM and TC-S （P＜0.05 or P＜0.01）； compared with the non-combined hyperlipidaemia group， CHD combined hyperlipidaemia group showed lower TB-S and TB-a （P＜0.05）； compared with non-combined heart failure group， CHD combined heart failure group showed lower TB-R， TB-G， TB-I， TB-L， and higher TB-a （P＜0.05 or P＜0.01）； compared with non-combined cerebral infarction group， CHD combined cerebral infarction group showed higher TC-CON， TC-ENT， TC-MEAN， and lower TC-ASM （P＜0.05 or P＜0.01）. ConclusionCompared to healthy individuals， patients with CHD tend to have darker tongue colours and rougher TC textures. Compared with non-comorbidity participants， those with primary hypertension tended to be lighter tongue colour and thicker tongue coating， those with carotid atherosclerosis had paler tongue body， those with type 2 diabetes mellitus had thinner tongue coating， those with fatty liver disease had paler tongue body and whiter tongue colour， those with hyperlipidaemia and heart failure had paler tongue colour， and those with cerebral infarction had rougher tongue texture.

This article reports the diagnosis and treatment of a case of acromegaly in a pregnant patient who took bromocriptine during pregnancy and delivered successfully. A retrospective summary of the clinical data and treatment outcomes before and after two pregnancies of the patient is provided. The patient took bromocriptine during the second pregnancy, and her condition remained stable. A baby girl was delivered by caesarean section at full term. The article suggests that pregnancy in acromegaly patients, after the stabilization of the condition, can lead to favorable outcomes. The use of dopamine receptor agonists during pregnancy does not increase adverse events during the perinatal period.

Objective To explore the effect of the physician-nurse-social worker linkage rehabilitation model on the psychological status in patients receiving methadone maintenance treatment(MMT).Methods Ninety-four patients who received MMT were enrolled and randomly divided into experimental group(n = 48)and control group(n = 46).The experimental group received physician-nurse-social worker linkage rehabilitation model intervention,while the control group received conventional methadone treatment service.The anxiety,depression and quality of life of the two groups were evaluated before the intervention,3 months and 6 months after the intervention.Results After 6 months of physician-nurse-social worker linkage rehabilitation mode intervention,the depression status and the anxiety status of the experimental group subjects were significantly improved compared with those before intervention,and both BDI and BAI scores were significantly lower than those of the control group subjects(P＜0.05).Moreover,the proportion of"had depression"and"had anxiety"in the experimental group were significantly lower than those in the control group(P＜0.05).After 6 months of intervention,the QOL-DA score of the experimental group subjects(183.77±8.90)was significantly higher than that of the control group sub-jects(174.76±11.14)(P＜0.01).Conclusion The physician-nurse-social worker linkage rehabilitation model had certain advantages in improving the psychological state of MMT patients,which is worthy of promotion.