In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Objective To investigate the epidemiological characteristics and diagnosis of imported Plasmodium malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Guangxi Zhuang Autonomous Region and Henan Province from 2014 to 2021, so as to provide insights into malaria control in these five provinces. Methods All data pertaining to malaria cases reported in five provinces of China were captured from Chinese Disease Control and Prevention Information System from 2014 to 2021, and the epidemiological characteristics of imported P. malariae and P. ovale malaria cases were analysed using a descriptive epidemiological method. The duration from onset of malaria to initial diagnosis, duration from initial diagnosis to definitive diagnosis, institutions of initial and definitive diagnoses, and proportion of correct malaria diagnosis at initial diagnosis were statistically analyzed. Results A total of 1 223 imported P. malariae and P. ovale malaria cases were reported in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021, there were 158 P. malariae malaria cases (12.92%) and 1 065 P. ovale malaria cases (87.08%). Totally 98.53% (1 205/1 223) of the imported malaria cases were from Africa, with Angola (18.99%, 30/158), Nigeria (11.39%,18/158), Cameroon (10.76%, 17/158), Ghana (10.13%, 16/158) and the Democratic Republic of the Congo (10.13%,16/158) as predominant countries where P. malariae malaria cases were from, and Ghana (23.19%, 247/1 065), Cameroon (14.74%, 157/1 065), Nigeria (9.39%, 100/1 065) and Angola (6.95%, 74/1 065) as predominant countries where P. ovale malaria cases were from. There were significant differences in the duration from onset of malaria to initial diagnosis (χ² = 27.673, P = 0.000) and duration from initial diagnosis to definitive diagnosis of P. malariae and P. ovale malaria cases (χ² = 29.808, P = 0.000), and the proportions of correct initial diagnosis of P. malariae and P. ovale malaria cases were 38.61% (61/158) and 56.53% (602/1 065). There were 74.69% (118/158) of P. malariae malaria cases with definitive diagnosis in county-, city-, and province-level medical institutions, and 79.25% (844/1 065) of P. ovale malaria cases with definitive diagnosis in county- and city-level medical institutions and county-level centers for disease control and prevention. Conclusions The imported P. malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021 were mainly returned from Africa and the proportion of correct diagnosis of P. malariae and P. ovale malaria was low at initial diagnosis. Persistent improvements in the diagnostic capability of malaria are required in medical institutions.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Purpose The aim of this study is to investigate the relationship between the expression of kinesin family member C1(KIFC1)in endometrioid carcinoma and clinicopathological features and prognosis of endometrioid carcinoma patients.Methods The expression of KIFC1 in 30 cases of paracancer-ous endometrium and 95 cases of endometrioid carcinoma was detected by immunohistochemical SP method.qRT-PCR and Western blot were used to detect the expression level of mRNA and protein of KIFC1 in 30 pairs of fresh cancer tissues and ad-jacent non-cancer tissues.Furthermore,the relationship between KIFC1 protein expression and survival time was analyzed by TC-GA database,and their clinicopathologic features were analyzed.Results The immunohistochemistry results showed the positive rate of KIFC1 in endometrioid carcinoma(61.05％)was signifi-cantly higher than that in the neighboring noncancerous tissue(13.33％),and the difference was statistically significant(P＜0.05).The expression of KIFC1 was correlated with myometrial invasion,FIGO stage and lymphatic metastasis(all P＜0.05).The relative expression of KIFC1 mRNA in endometrioid carci-noma(2.99±0.59)was significantly higher than that in the neighboring noncancerous tissue(1.00±0.29),and there was significant difference(P＜0.05).The relative expression of KIFC1 protein in endometrioid carcinoma(1.70±0.36)was significantly higher than that in the neighboring noncancerous tissue(0.72±0.17),and there was significant difference(P＜0.05).Furthermore,elevated KIFC1 expression was positive-ly correlated with a poorer prognosis.Conclusion KIFC1 is upregulated in endometrioid carcinoma and associated with poor prognosis of patients,KIFC1 was expected to be a potential ther-apeutic target and prognostic indicator for endometrioid carcino-ma.

Objective To investigate the relationship among circulating soluble major histocompatibility complex class Ⅰ-related chain A(sMICA),soluble major histocompatibility complex class Ⅰ-related chain B(sMICB),the activity of systemic lupus erythematosus(SLE)and autoantibodies.Methods A total of 156 SLE patients(SLE group)and 103 healthy volunteers(control group)who underwent physical examination in outpatient physical examination center were selected from the Qianjiang Hospital Affiliated to Chongqing University from January 2020 to January 2023.According to SLE disease activity score(SLEDAI),these SLE patients were divided into mild activity group(n=43),moderate activity group(n=69),and severe activity group(n=44).Serum levels of sMICA and sMICB,and the proportion of autoantibodies and peripheral blood NK cells were detected.Spearman or Pearson method was used to analyze the correlation among sMICA,sMICB,score,autoantibodies and peripheral blood NK cells proportion.Receiver operating characteristics(ROC)curve was used to evaluate the value of sMICA and sMICB in the diagnosis of SLE activity.Results Serum sMICA(173.65±23.92 pg/ml)and sMICB(96.35±15.74 pg/ml)levels in SLE group were higher than those in control group(32.51±6.27 pg/ml,12.03±2.47 pg/ml),while the proportion of CD3-CD56+NK cells(12.02％±2.65％)in peripheral blood was lower than that in control group(18.35％±3.71％),and the differences were statistically significant(t=58.498,53.897,-16.010,all P＜0.05).Serum sMICA and sMICB levels in severe active group were higher than those in moderately active group and mildly active group(t=8.192,12.352;19.652,23.742,all P＜0.05),and the proportion of CD3-CD56+NK cells in peripheral blood was lower than that in moderate and mild active groups(t=8.154,10.658,P＜0.05).The differences in positive rates of anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody in SLE patients with different disease activities were significant(x2=8.795,7.216,7.539,8.946,all P＜0.05).Serum sMICA and sMICB levels in SLE patients were positively correlated with SLED AI score,anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody(r=0.206～0.402,all P＜0.05),and negatively correlated with the proportion of CD3-CD56+NK cells in peripheral blood(r=-0.563,-0.427,all P＜0.05).The areas under the curve of SLE in severe active group diagnosed by sMICA and sMICB alone were 0.652 and 0.704,respectively.The area under the curve of SLE in severe active group diagnosed by sMICA and sMICB combined with SLE was 0.812,which was higher than that by the single diagnosis(Z=3.050,2.346,all P＜0.05).Conclusion The increased serum sMICA and sMICB levels in SLE patients were associated with the increased positive rate of SLE autoantibodies,the decreased proportion of NK cells in peripheral blood and the enhanced disease activity,which could be used as potential markers of SLE.

In the study of age estimation in living individuals,a lot of data needs to be analyzed by mathematical statistics,and reasonable medical statistical methods play an important role in data design and analysis.The selection of accurate and appropriate statistical methods is one of the key factors af-fecting the quality of research results.This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics,difference analysis,consistency test and multivariate statistical analysis,as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals,and summarizes the relevance and application prospects between medical statistical methods and machine learning methods.This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.