OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

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

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 investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

The bone-touching acupuncture method, as one of the five-body acupuncture techniques, is widely used and highly effective in the treatment of brain diseases, though its theoretical foundation has been lacking. This paper explores the close connection between bones and the brain in both physiological and pathological states, as described in traditional Chinese medicine (TCM) classics, and explains the "bone-brain axis" concept within the framework of TCM. It summarizes the effects and characteristics of the five-body acupuncture techniques, traces the origins and modern applications of the bone-touching acupuncture method, and discusses its theoretical basis for treating brain diseases. The aim is to provide a reference for future clinical and mechanistic research on bone-touching acupuncture in brain disease treatment and to offer new perspectives and approaches for acupuncture treatment of brain diseases.
Humans ; Acupuncture Therapy/methods* ; Brain/physiopathology* ; Brain Diseases/physiopathology* ; Bone and Bones/physiopathology* ; Medicine, Chinese Traditional/methods*

Objective To explore the relationship between the expression of M2 pyruvate kinase(PKM2)and E-cad-herin(E-cadherin)in tumor tissues and the clinicopathology and prognosis of breast cancer patients.Methods 447 patients with breast cancer admitted from February 2020 to February 2022 were selected as the objects of this study.Breast cancer tissues and adjacent tissues of patients were taken,and patients were divided into good prognosis group(261 cases)and poor prognosis group(186 cases)according to the prognosis of patients.Immunohistochemistry was used to determine the expression of PKM2 and E-cadherin in the tissues of the patients,and the patients were followed up for 6 months.The patients were divided into groups according to whether the patients had recurrence and metastasis,and the relationship between the expression of PKM2 and E-cadherin in the breast cancer tissues of the patients and the clinicopathology was explored.The expression of PKM2 and E-cad-herin protein between breast cancer tissue and adjacent tissue,and between good prognosis group and poor prognosis group were compared,and the correlation between PKM2 and E-cadherin protein expression and poor prognosis of patients was explored.Results There were no differences in the expression of PKM2 and E-cadherin in breast cancer patients with different ages,tumor sites and tumor sizes(P＞0.05).The positive rate of PKM2 protein expression was higher and the positive rate of E-cadherin protein expression was lower in postmenopausal,middle and highly differentiated,stage I to II and no lymph node metastasis(P＜0.05).The positive rate of PKM2 in patients with poor prognosis was 94.62%,higher than 81.23%in patients with good prognosis;The positive rate of E-cadherin in patients with poor prognosis was 30.65%,which was lower than 46.36%in patients with good prognosis(P＜0.05).By Spearman correlation coefficient analysis,poor prognosis was positively correlated with the positive rate of PKM2 in breast cancer tissues(r=0.195,P＜0.001),and negatively correlated with the positive rate of E-cad-herin protein(r=-0.158,P=0.001).Conclusion PKM2 and E-cadherin protein expression in tumor tissues of breast canc-er patients has some link with the clinicopathology of patients,and there is some correlation with patient prognosis.

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.

ObjectiveTo identify potential distribution areas for wild Panax ginseng cultivated under forest in Liaoning province， China， and analyze the ecological factors of spatial stratified heterogeneity affecting its ecological suitability and quality suitability. MethodWild Panax ginseng samples cultivated under forest were collected from 33 cultivation bases in Liaoning province. The Maxent maximum entropy model and ArcGIS were used to delineate the ecological suitability zones. Correlation analysis was performed on seven indicators and 110 ecological factors. Variables with significant correlation （P<0.05） were used to build partial least squares regression analysis models. A comprehensive quality zoning was conducted using the analytic hierarchy process （AHP）. The geographic detector was employed to analyze the interactions among dominant ecological factors of spatial stratified heterogeneity affecting habitat suitability， quality suitability， and the ecological driving factors. ResultVegetation type was the most influential ecological factor for delineating the ecological suitability zones for wild Panax ginseng in Liaoning province. The main ecological suitability areas for wild Panax ginseng cultivated under forest were located in the northeast， east， and southeast regions along the line from Xifeng County to Gaizhou City. The comprehensive quality suitability of wild Panax ginseng cultivated under forest was highest in Kuandian County and Huanren County and gradually decreased to the northwest and southwest. Within the delineated regions， the suitability conditions and comprehensive quality of wild Panax ginseng cultivated under forest were primarily influenced by the interactions between radiation and precipitation factors. The content of the measured samples was significantly higher than the standards in the 2020 edition of the Chinese Pharmacopoeia， indicating the high overall quality of wild Panax ginseng in Liaoning Province. ConclusionAccording to the zoning and prediction results， areas in Fengcheng City， Xiuyan County， Zhuanghe City， Liaoyang County， Tieling County， Xifeng County， Gaizhou City， Haicheng City， and Dashiqiao City showed large potential distribution areas with high quality， making them highly promising for wild Panax ginseng cultivation. However， further experimental verification is required. The zoning results can provide insights for research on habitat suitability and comprehensive quality accumulation of wild Panax ginseng cultivated under forest， as well as guidance for the search for potential cultivation areas and industrial development of wild Panax ginseng in Liaoning Province.

ObjectiveTo analyze the dynamic response relationship between urban development and mortality rate in Shanghai， and to predict the trend of mortality rate changes. MethodsBy analyzing the total mortality rate （TMR）， gross domestic product （GDP） and socio-demographic index （SDI） in Shanghai from 1978 to 2017， a vector autoregressive （VAR） model was constructed to evaluate the impact of urban development on the mortality rate. ResultsThe fitted R2 of the VAR model was 0.92. The short-term effect of GDP on the improvement of death level was negative， while the long-term effect was positive， and the SDI was negative regardless of the short-term and long-term effects. By the tenth year， GDP and SDI contributed 10.61% and 27.25% to TMR changes， respectively. The model predicted that the mortality rate in Shanghai would be 9.17 per thousand by 2030. ConclusionLong-term economic growth can effectively promote a decline in population mortality. However， as the economy develops vigorously， the adverse effects of declining birth rates and population aging on population health during the era of high-level population development should not be ignored.

ObjectiveTo investigate the characteristics of gender difference and the trend of the mortality rate of senile dementia in registered population in Shanghai from year 2002 to 2018， and to provide the basis for formulating relative intervention measures before and after senile dementia from an public-health view. MethodsBased on the collected data of death registration， focused on the senile dementia disease codes F03，G30.0，G30.1，G30.8，G30.9 according to The International Classification of Diseases 10th revision （ICD-10）. We analyzed the characteristics of gender difference in the mortality rate of senile dementia in registered population in Shanghai from year 2002 to 2018. According to ASR， we calculated the standardized mortality rate of senile dementia， and used the chi-square test to compare the difference between the gender mortality rates. The trend and the turning point of the mortality rate of senile dementia were determined by linear regression analysis by Join-point. ResultsThe crude mortality rate of senile dementia in the registered population in Shanghai from year 2002 to 2018 was 5.46/10⁵， 3.50/10⁵ in males and 7.43/10⁵ in females. The standardized mortality rate of senile dementia was 2.61/10⁵， 1.67/10⁵ in males and 3.56/10⁵ in females. The trend of the standardized mortality rate of senile dementia in 17 years decreased ［APC=-5.5（-6.5，-4.5）%，P<0.01］. The trend of the standardized mortality rate of senile dementia decreased in both males ［APC=-4.9（-6.2，-3.6）%，P<0.01］ and females ［APC=-5.9（-6.9，-4.9）%，P<0.01］. The trend of the gender difference decreased ［APC=-6.8（-8.2，-5.3）%，P<0.01］. The mortality rate of senile dementia was higher in females than in males ［（χ²=33.63，P<0.01）］. ConclusionThe mortality rate of senile dementia in females is higher than in males in Shanghai， though the trend of the gender difference decreased. This gender difference is worth of attention.