ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P＜0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P＜0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)％of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)％.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)％of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)％.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To establish the reference intervals for test indicators of thyroid function,namely thyroid stimulating hormone(TSH),free thyroxine(FT4),and free triiodothyronine(FT3),in the children aged 0 to 15 years old in Nanning,China.Methods A total of 1 289 healthy children aged 0 to 15 years old who attended the Guangxi International Zhuang Medicine Hospital Affiliated with Guangxi University of Chinese Medicine from October 2018 to August 2023 were selected.The concentrations in serum TSH,FT4,and FT3 were measured by chemiluminescent microparticle immunoassay(CMIA).According to the Clinical and Laboratory Standards Institute(CLSI)EP28-A3c guideline,the nonparametric percentile method was used to establish the reference intervals for TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area.Results The established reference intervals were as follows:TSH(male):0 to＜1 month:0.88-7.81 μIU/mL,1 month to 15 years:0.59-5.06 μIU/mL;TSH(female):0 to＜1 month:0.93-8.42μIU/mL,1 month to 15 years:0.60-4.30 μIU/mL.FT4(male):0 to＜1 month:0.99-1.92 pg/mL,1 month to 15 years:0.86-1.33 pg/mL;FT4(female):0 to＜1 month:1.05-2.06 pg/mL,1 month to 15 years:0.85-1.37 pg/mL;FT3:0 to＜1 month:2.16-4.24 pmol/L,1 month to＜11 years:2.75-4.49 pmol/L,11 to 15 years:2.45-4.34 pmol/L.Significant differences were observed among different gender and age groups for TSH,FT4,and FT3 levels(P＜0.05).Conclusion This study successfully established the refer-ence intervals of TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area,which were significantly different among various gender and age groups.

Objective:To retrieve and summarize the best evidence for nursing of hematopoietic stem cell reinfusion in children.Methods:Clinical decisions, guidelines, recommended practices, evidence summaries, systematic reviews, and expert consensuses on nursing of hematopoietic stem cell reinfusion in children were searched in Chinese and English databases as well as related websites such as British Medical Journal (BMJ) Best Practice, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, Guidelines International Network, Scottish Intercollegiate Guidelines Network, Joanna Briggs Institute Evidence-Based Health Care Center Database, UpToDate, CINAHL, Embase, PubMed, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from database establishment to March 2023. Two researchers independently conducted literature quality evaluation, identified the included literature, extracted evidence item by item, and translated, organized and summarized the evidence.Results:A total of nine articles were included, including two clinical decisions, two expert consensuses, four guidelines, and one evidence summary. 24 pieces of evidence were summarized from six aspects, consisting of child preparation, stem cell preparation, item preparation, nursing during reinfusion, nursing after reinfusion, and evaluation and education.Conclusions:The best evidence for nursing of hematopoietic stem cell reinfusion in children involves a wide range of aspects. Managers, clinical medical and nursing staff should apply evidence based on specific medical situations in order to safely and reasonably perform hematopoietic stem cell reinfusion.

Background China is witnessing an accelerated aging process and an increasingly serious situation of Parkinson's disease. Research on the pre-disease stage and its related influencing factors has gained more and more attention. Objective To analyze the current situation of prodromal Parkinson's disease (pPD) of people aged 55 years and above in four provinces of China, and to explore its influencing demographic and socio-economic characteristics. Methods Using the data of Community-based Cohort Study on Nervous System Disease in 2020, a total of 10724 participants with complete data on demographic and socio-economic factors and risk factors on Parkinson's disease were selected. Based on the criteria recommended by the International Parkinson and Movement Disorder Society (MDS), we evaluated risk level (i.e., post-test probability) of pPd, prevalence of possible or probable pPD, and number of pPD-related risk/prodromal markers in the participants. Multiple linear regression and multiple logistic regression models were used to analyze the influencing socio-demographic factors of risk level of pPd and prevalence of possible or probable pPD, and Poisson regression and multinomial logit regression models were used to analyze the influencing socio-demographic factors of the number of pPD-related risk/prodromal markers in the total sample, men, and women, respectively. Results The median (P₂₅, P₇₅) of post-test probability of pPD in 2020 was 0.78% (0.42%, 1.66%), the prevalence rate of possible or probable pPD was 0.34%, and 69.03% of the participants reported 3-5 pPD-related risk/prodromal markers. The post-test probabilities of men, those with older age, lower education level, per capita monthly household income < 1000 yuan, urban residency, or without active employment were higher (P<0.05). Men and being aged ≥ 75 years had a higher prevalence of possible or probable pPD (P<0.05). The OR of possible or probable pPD was 8.404 (95%CI: 2.839−24.879) in subjects aged ≥ 75 years versus those aged 55−64 years. Males, those without active employment, being less educated, with older age, and urban residents were more likely to report pPD-related risk/prodromal markers than those of the opposite groups (P<0.05). Conclusion Men, subjects aged ≥75 years, those with lower education level, urban residents, and those without active employment have higher risk levels of pPD and are more likely to report pPD-related risk/prodromal markers among people aged 55 years and above in the four provinces of China, poor economic situation is also associated with higher risk levels of pPD.

Background Gastrointestinal microbiota plays an important role in the development of Parkinson's disease (PD), and dietary factors have a great impact on intestinal micro ecology. At present, few studies focus on red meat and PD, especially prodromal PD (pPD). Objective To understand the relationships of the intake of red meat and processed meat products with pPD and the number of risk/prodromal markers, and to explore the association of dietary factors with pPD. Methods Based on the data of Community-based Cohort Study on Nervous System Disease in 2018 and 2020, adults aged 55 years and older with complete demographic information, dietary survey information, and information on risk factors related to PD were selected from four provinces of China. After excluding those reporting abnormal total energy intake or those reporting alcohol drinking or abused drugs for a long period of time, and confirmed mental diseases with prescribed drugs, a total of 10003 subjects were included. Food frequency questionnaire was used to calculate the intake of red meat and processed meat products. The pPD-related risk/prodromal markers were selected following the International Parkinson and Movement Disorder Society criteria for pPD, and the risk level and the number of markers of pPD were then calculated. The relationship between the intake of red meat and processed meat and the risk level of pPD was analyzed by multiple linear regression. The relationship between the intake of red meat and processed meat and the pPD marker number groups was analyzed by multinomial logit regression model. Results In 2018, the intake of red meat and processed meat was 28.57 g·d⁻¹ in the target population. In 2020, the median of the number of risk/prodromal markers was 3, and the median M (P₂₅, P₇₅) of the posterior probability of pPD was 0.74% (0.42%, 1.49%). The multiple linear regression analysis showed that the higher the intake of red meat and processed meat, the higher the risk level of pPD in follow-up (b=0.021, P<0.05). The multiple logit regression model showed that compared with the lowest quartile (Q1), the highest quartile (Q4) group of red meat and processed meat intake were more likely reporting 3−5 risk/prodromal markers than ≤ 2 risk/prodromal markers (OR=1.185, 95%CI: 1.015−1.382). Conclusion The intake level of red meat and processed meat is related to the risk level of pPD, and a higher intake of red meat and processed meat may be a potential risk factor of pPD.

Background It has been reported that a high intake of dairy products might be associated with an increased risk of Parkinson's disease (PD) in foreign studies, but no such study has yet been conducted on prodromal Parkinson's disease (pPD) and the Chinese population. Objective To investigate the prospective relationship between the intake of dairy products and pPD among people aged 55 and above in four provinces of China. Methods The research data were obtained from the baseline 2018 and follow-up 2020 surveys of Community-based Cohort Study on Nervous System Disease. A total of 9984 residents were selected who participated in both waves of surveys and had complete data on demographics, dietary products intake, and risk factors for PD. We evaluated the risk level and the numbers of related risk/prodromal markers of pPD in the participants based on a criteria recommended by the International Parkinson and Movement Disorder Society (MDS). Food Frequency Questionnaire was used to obtain food consumption data in the past 12 months, and the intake of dairy products was calculated and divided into non-consumption and tertiles of consumption (T1, T2, and T3 from low to high). Multiple linear regression was used to analyze the association between baseline dairy intake and risk level of follow-up pPD. Poisson regression and multinomial logit regression models were used to analyze the relationship of baseline dairy products and the number of risk/prodromal markers of follow-up pPD in the population, and multiple logistic regression was used to analyze each risk/prodromal marker of follow-up pPD according to baseline levels of dairy products intake. Results The percentage of residents without dairy products consumption was 58.02% in 2018, and the dairy products intakes were relatively high among residents being female, aged 55 to 74 years, with an education level of middle school and above, with a per capita monthly household income ≥ 1000 yuan, living in urban areas, and without active employment (P<0.05). The median risk level of pPD was 0.74% in 2020, and the proportion of residents with 3 to 5 markers was 66.74%. The multiple linear regression analysis results suggested no association between baseline dairy intake and follow-up risk level of pPD. The Poisson regression model showed that the high dairy products intake group at baseline (T3, median=250.00 g·d⁻¹) was found to be 1.159 (95%CI: 1.065~1.261, P_trend<0.001) times more likely to have the risk/prodromal markers of pPD at follow-up than non-consumers. When the number of markers was grouped, no statistically significant association was found by multiple logistic regression analysis. Conclusion Although high dairy products intake levels might be associated with pPD risk/prodromal markers among people aged 55 and above in four provinces of China, no direct association is found between dairy products intake and pPD risk levels in this study.

Background Changes in cognitive function exist before the onset of clinical Parkinson's disease. However, studies on association between cognitive function and prodromal Parkinson's disease (pPD) are limited. Objective To estimate probability of pPD and assess its association with global and domain cognitive function in Chinese elders. Methods Data were drawn from the Community-based Cohort Study on Nervous System Disease 2018 (baseline) and 2020 (follow-up). We selected 3911 residents aged 55 and above who participated the two waves, without Alzheimer's disease and Parkinson's disease, and with completed information on demographics, disease history, cognitive function test, and risk factors of Parkinson's disease. Cognitive function was assessed using the Chinese version of Montreal Cognitive Assessment Scale. Calculation of probability of pPD and assessment of possible (probability between 30% and <80%) or probable (probability ≥80%) pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multiple linear regression model was employed to analyze the association between baseline cognitive function and follow-up probability of pPD. Results The medians of scores of baseline global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention, and orientation were 23, 12, 9, 6, 5, 14, and 6, respectively. The median of follow-up probability of pPD was 0.87%, and the proportion of participants with possible or probable pPD was 0.4%. The differences in the distribution of follow-up probability of pPD were significant in groups by baseline global cognitive score quartiles (χ²=21.68, P<0.001). A higher baseline global cognitive score was considerably related to a lower follow-up probability of pPD, b(95%CI)=0.994(0.988~0.999), P=0.040. After adjusting for selected confounders, the results of multiple linear regression analyses showed that the probability of pPD in the highest quartile group was decreased by 10.7% (b=0.893, 95%CI: 0.794-0.992, P=0.034) relative to the lowest quartile group, and the trend was significant (trend P=0.031). Higher baseline index scores of execution, attention, and orientation were highly related to a lower follow-up probability of pPD (all P<0.05). Conclusion Declines in global cognitive function and cognitive domains of execution, attention, and orientation may associate with a higher probability of pPD in middle-aged and elderly population, which suggests the significance of cognitive intervention in early stage for pPD prevention.