BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023.Methods:The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases.Results:A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years ( χ2=5.33, P=0.021; χ2=48.14, P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions:From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

Objective:To explore the effect of ointment massage on the postoperative recovery of newborns who had intestinal tract operation, aim to construct an effective post-operative ointment and massage scheme and to enrich the content of enhanced recovery after surgery in the field of newborns.Methods:Delphi expert inquiry method was used to construct the ointment message scheme. A total of 64 newborns undergone intestinal surgery from May 2022 to May 2023 in Guangdong Women and Children Hospital were selected as study subjects and divided into routine group (34 cases) and ointment group (30 cases) by random number table method. In addition to routine treatment and nursing, the newborns in the ointment group also received ointment massage. The postoperative gastrointestinal drainage volume, fasting days, the first feeding time, hospital stay and the number of cases of vomiting and abdominal distension between the two groups were compared.Results:A total of 16 experts with (38.93 ± 5.13) years old were inquired, 6 males and 10 females. The effective questionnaire response rates for the two rounds of expert inquiry were 16/16 and 15/16, the expert authority coefficients were both≥0.80, the Kendall′s W coefficients were 0.117 and 0.107, with statistically significant differences (both P<0.05). A ointment message scheme consisting of 8 acupoints and 7 kinds of traditional Chinese medicines was determined. In the routine group, there were 19 males and 15 females with (268.47 ± 11.27) gestational age. In the ointment group, there were 20 males and 10 femles with (271.93 ± 10.36) gestational age. The postoperative gastrointestinal drainage volume, fasting days, the first feeding time and the hospital stay in the ointment group were 74.0 ml, 6.0 d, 158.5 h and 13.0 d, which had significant differences with the 184.5 ml, 7.5 d, 192.0 h, 16.5 d in the routine group ( Z values were 2.07-2.45, all P<0.05). The incidence of vomiting and abdominal distension in the ointment group were both 8 cases, which were lower than the 19 and 18 cases in the routine group with a statistically significant difference ( χ2 = 5.58, 4.56, both P<0.05). Conclusions:The ointment massage in this study has a positive impact on the recovery of newborn infants after intestinal surgery, with high safety, in line with enhanced recovery after surgery concept, and is worthy of promotion.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

ObjectiveTo investigate the effects of Buyang Huanwutang （BYWHT） on reducing inflammatory injury and improving neurological function after cerebral ischemia-reperfusion in rats via activating the adiponectin （APN） pathway. MethodMale SD rats were randomized into sham， model， BYHWT （16 g·kg^-1， twice a day）， and BYHWT + APN inhibitor （GW9662） groups. In the sham group， blood vessels were isolated. The rat model of middle cerebral artery occlusion （MCAO） was established. The rats in the BYHWT+GW9662 group was treated with subcutaneous injection of GW9662 at 4 m·kg^-1 30 min before MCAO surgery and BYHWT at 16 g·kg^-1 by gavage after MCAO surgery， once in the morning and once in the evening. The immunofluorescence （IF） assay was employed to observe the expression of adiponectin receptor 1 （AdipoR1） and the colocalization of AdipoR1 with neuronal nuclei （NeuN） and ionized calcium binding adaptor molecule 1 （Iba1） in the brain. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of APN in the serum and brain. The balance beam test was carried out to examine the balance ability， and the grasping test to assess the recovery of limb strength. The immunofluorescence assay was used to detect the expression of myeloperoxidase （MPO）. Western blot was employed to determine the expression of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， IL-6， and IL-10 and in the brain. ResultCompared with the sham group， the modeling promoted the expression of AdipoR1 （P<0.01）， lowered the APN levels in the serum and brain （P<0.05， P<0.01）， increased the score in the balance beam test （P<0.01）， and decreased the grasping strength of forepaw （P<0.01）， which were accompanied with increased MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and decreased IL-10 level （P<0.01）. Compared with the model group， BYHWT promoted the expression of AdipoR1 （P<0.01）， elevated APN levels in the serum and brain （P<0.05， P<0.01）， and increased the grasping strength of forepaw （P<0.01）， which were accompanied with lowered MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and elevated IL-10 level （P<0.01）. All the above effects were partially blocked by GW9662. ConclusionBYHWT can reduce inflammatory injury and improve neurological function in the rat model of cerebral ischemia-reperfusion by activating the APN pathway.

Objective To establish a dual wavelength HPLC method to compare the content changes of seven active components:monoglycoside,loganin,swertin,paeoniflorin,gallic acid,5-hydroxymethyl furfural and paeonol in Liuwei Dihuang Decoction(hereinafter referred to as"Liuweidihuang Decoction")before and after the preparation of Cornus wine;To explore the effect and mechanism of Liu(Shan)and Liu(Jiu)on 90 days after ovariectomy in postmenopausal osteoporosis model rats.Methods ①The contents of seven active ingredients in the Cornus wine mixed with Liuwei Dihuang Decoction were determined by dual wavelength HPLC.Chromatographic conditions:hypersil C18 chromatography(4.6 mm×250 mm,5 μm),mobile phase acetonitrile-0.3%phosphoric acid,gradient elution(0-7 min,0%-8%acetonitrile;7-15 min,8%-10%;15-20 min,10%-15%;20-30 min,15%-23%;30-50 min,23%-45%),flow rate 0.6 mL·min-1,detection wavelength:240 nm(monoglycoside,loganin,swertin,paeoniflorin),274 nm(gallic acid,5-hydroxymethyl furfural,paeonol),column temperature 30℃,injection volume 20 μL.②6-8 month old SD rats,divided into sham-operated group,model group,positive drug group,shanshuang flesh with Liuwei Dihuang Decoction group(liu(shan)group)and wine cornelian flesh withLiuwei Dihuang Decoction group(liu(wine)group),dosing started on the 5 d after ovariectomy,weighed weekly,and 5 rats from each group were taken at 90 d after surgery,weighed,anaesthetized,serum taken,bilateral femurs,and organs(uterus,spleen,liver,both kidneys and heart)were weighed.Serum calcium(Ca),phosphorus(P)and estradiol(E2)levels were measured using a fully automated biochemical instrument and chemiluminescent microparticle immunoassay,respectively;bone mineral density(BMD)values were measured using a dual-energy X-ray bone densitometer.HE staining was used to observe the morphological changes of bone tissue in rats.Results ①All the seven potent ingredients mentioned above were contained in the Liuwei Dihuang Decoction before and after the wine preparation of Cornu Cervi Pantotrichum,and the total content of the seven potent ingredients in liu(wine)was higher than that in liu(shan)(P<0.01).Among them,gallic acid and 5-hydroxymethylfurfural were higher in Liu(Jiu)than in Liu(Shan)(P<0.01),while the content of monosidine was lower than in Liu(Shan)(P<0.01).②Comparison with the sham-operated group:90 d after surgery,the serum Ca,P,E2 levels and uterine index of rats in the model group decreased(P<0.01),the BMD value decreased(P<0.01),and the degree of structural damage to bone tissue The degree of damage to the bone tissue structure was deepened,manifested by enlargement of the bone marrow cavity,gradual increase of adipocytes,dilution of the bone trabeculae arrangement,reduction of the number of bone trabeculae or even fracture.③Compared with the model group,90 d after surgery,the serum E2,Ca,P levels and uterine index of the rats in the liu(shan)and liu(wine)groups increased(P<0.05),the bone tissue structure of the liu(shan)and liu(wine)groups improved significantly,and the BMD value increased significantly(The liver and spleen indices of the liu(wine)groups increased(P<0.05).Conclusion The combination of the wine preparation of Cornus officinalis and its use in the formula of LiuWei Di Huang Decoction both contain monosidine,strychnine,sweretin,paeoniflorin,gallic acid,5-hydroxymethyl furfural(5-HMF)and tannin,and can effectively interfere with PMOP.Among them,the anti-osteoporotic effect of Liu Wei Di Huang Tang,which was formulated with wine and dogwood,was better than that of Liu Wei Di Huang Tang,which was formulated with Cornus officinalis,and the former contained more 5-HMF and gallic acid than the latter,which may provide some experimental basis for the selection of wine and dogwood in the 2020 edition of the Pharmacopoeia and the clinical application of Liu Wei Di Huang Tang in the prevention and treatment of PMOP.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People

Objective To analyze the clinical features of 35 cases of Kennedy's disease and the correlation be?tween clinical features and CAG repeat size to strengthen the understanding of KD and to avoid misdiagnosis and delayed diagnosis.Methods Clinical data, including clinical signs and symptoms ,serum lipid, serum sex hormone level, electro?myography, the number of CAGs and (amyotrophic lateral sclerosis muscular atrophy,ALS) rating scale were collected from 35 patients genetically diagnosed of Kennedy disease and proceed system analysis. Results Patients with KD were adult onset with the average age of (40.77 ± 8.57) years and the average confirmed course were (8.32 ± 4.17) years. Forty-two point nine percent of the patients had family history. Clinical features included medulla oblongata and spinal muscular atrophy and weakness, limbs tremor, perioral muscles twitch and endocrine function and metabolic disorders in some cases. Creatine kinase, triglyceride, low density lipoprotein, follicle estrogen and prolactin were significantly in?creased compared to healthy adults (P:0.000,0.018,0.000,0.000,0.003). The number of CAG repeat was negatively correlated with the onset age (r=-0.549, P=0.001) but not associated with the illness severity (ALS rating scale) (r=0.001, P=0.998). ALS score was negatively correlated with course of disease(r=-0.540, P=0.001).Conclusions Chinese KD pa? tients share similar clinical phenotypes with those of other races but exhibit slightly different clinical characteristics. The length of the CAG repeat influences age at onset but not the severity of disease. Severity of disease is related to the course of disease.

Objective To describe the clinical features, differential diagnosis and therapeutic method of Madras motor neuron disease (MMND) to improve the understanding of MMND. Methods We retrospectively summarized the clinical data of 3 MMND patients. and conducted the related literature review to compare the similarities and differences on clinical features between our cases and foreign MMND patients. Results Patients in the present study were adult-on?set without definite family history. The main manifestations were multiple lower cranial nerve palsies along with weakness and wasting of proximal limbs. Bifacial palsy and dysarthria were most presented in patients, while definite hearing im?pairment was rarely seen. Two patients had fasciculation and atrophy in tongue and one presented with dysphagia. Weak?ness and atrophy were more frequently presented in upper extremities than in lower limbs. All patients had signs of upper motor neuron damage. The level of creatine kinase (CK) moderately increased in one case. Electromyography (EMG) de?tected a widespread neuronal damage in all patients. MMND should be differentiated from Amyotrophic Lateral Sclerosis, Kennedy Disease and Brown–Vialetto–van Laere Syndrome. Intravenous immunoglobulin therapy showed effective in some cases to some extent. Compare to foreign MMND patients, bifacial weakness at onset was more frequently presented in our patients, but hearing impairment was absent. Conclusion The clinical features of MMND include weakness and at?rophy of limbs, involvement of facial and bulbar muscles, pyramidal dysfunction and hearing impairment. Some clinical manifestations of our patients are different from foreign MMND patient.