This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background and objective The incidence rate of lung cancer in Xuanwei has been continuously in-creasing in recent years,and it also features high incidence across all age groups and high mortality rates among female lung cancer patients.Therefore,the search for more stable biomarkers for the diagnosis of Xuanwei lung cancer holds tremendous clinical application prospects.This study aims to explore the clinical application value of these four microRNAs(miRNAs)in-dividually and in combination with traditional lung cancer tumor markers in the detection and diagnosis of Xuanwei lung can-cer.Methods By detecting the expression levels of four miRNAs and five traditional lung cancer tumor markers in the serum of 45 Xuanwei lung cancer patients and healthy physical examination participants,the Logistic regression model was employed to comprehensively evaluate the sensitivity,specificity,diagnostic efficacy,and other relevant statistical indicators of the four miR-NAs in the diagnosis of Xuanwei lung cancer.Results Among the individual miRNAs,miR-4646-5p and miR-3654 showed significant differences in expression levels between the Xuanwei lung cancer group and the control group(P＜0.05).miR-3654 demonstrated the best diagnostic performance with a sensitivity of 86.7％ ,specificity of 82.2％ ,and an area under the curve of 0.847.Combining miR-3654 with miR-4646-5p and carcinoembryonic antigen(CEA)resulted in the highest diagnostic ef-ficacy for Xuanwei lung cancer,with a sensitivity of 73.3％ ,specificity of 93.3％ ,area under the curve of 0.901,and a positive predictive value of 91.7％ .Conclusion Among the four miRNAs,serum miR-3654 exhibits the best diagnostic efficacy for Xuanwei lung cancer.Combined with miR-4646-5p and CEA,its diagnostic value for Xuanwei lung cancer can be effectively enhanced,making it a promising screening indicator for Xuanwei lung cancer.

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective To investigate the effects of Astragalus polysaccharides(HPS)on farnitol X receptor(FXR)-small heterodimer chaperone receptor(SHP)signaling pathway and key proteins of glucose and lipid metabolism in diabetic rats.Methods Twelve male Wistar rats were randomly selected as blank group,and the remaining 60 rats were fed with a one-time intrabitoneal injection of streptozotocin(STZ,50 mg·kg-1)combined with a high-sugar and high-fat diet to replicate the diabetic rat model.The model rats were randomly divided into model group,positive control group(400 mg·kg-1·d-1 Bifidobacterium quadruple viable bacterial tablet suspension),experimental-H,-M,-L groups(200,100 and 50 mg·kg-1·d-1 HPS suspension),respectively.Blank group and model group were given equal volume of pure water once a day for 8 weeks.Blood glucose(Glu)was measured before and after gavage.Real-time fluorescent polymerase chain reaction(RT-PCR),Western blot were used to detect the mRNA and protein expression level of FXR,SHP,antiperoxisomal proliferator-activated receptor α(PPARα),antiphosphoenolpyruvate carboxylkinase(PEPCK),sterol regulatory receptor binding protein-1c(SREBP-1c),glucose 6 phosphatase(G6Pase).Results Glu levels in normal group,model group,positive control group and experimental-H group after treatment were(7.66±0.61),(29.25±1.64),(23.31±3.02),(19.31±5.13)mmol·L-1,respectively;the relative expression levels of FXR mRNA in liver tissues were 1.00±0.04,0.44±0.03,0.61±0.06,0.87±0.03,respectively;the relative expression levels of SHP mRNA were 1.00±0.04,0.40±0.01,0.67±0.01,0.67±0.02;the relative expression levels of G6Pase mRNA in liver tissues were 1.00±0.06,3.00±0.08,1.87±0.03,1.44±0.05,respectively;the relative expression levels of PEPCK mRNA in liver tissues were 1.00±0.04,1.88±0.03,1.31±0.02,1.23±0.04,respectively;the relative expression levels of SREBP-1c mRNA in liver tissues were 1.00±0.04,1.90±0.01,1.26±0.03,1.06±0.04;the relative expression levels of PPARα mRNA in liver tissues were 1.00±0.02,0.16±0.01,0.45±0.01,0.96±0.03,respectively.Compared with blank group,positive control group and experimental-H group,there were statistically significant differences in the above indexes between model group and blank group(all P＜0.01).The protein expression trend of FXR,SHP,G6Pase,PEPCK,SREBP-1c,PPARα was consistent with mRNA expression.Conclusion HPS may regulate FXR-SHP signaling pathway in liver tissue,inhibit the expression of key proteins of glucose and lipid metabolism,promote lipid oxidation,improve Glu and protect liver tissue in diabetic rats.

Objective To analyze the economic burden due to healthcare-associated infection(HAI)in low birth weight(LBW)infants,and provide theoretical basis for formulating HAI related policies.Methods The data of LBW infants in a tertiary first-class hospital from January 2018 to December 2022 were retrospectively collected.Propensity score matching method and marginal analysis were adopted to evaluate the economic losses in LBW in-fants and hospitals due to HAI.Results A total of 1 048 LBW infants were included in analysis,124 of whom had HAI,with HAI incidence of 11.8％.A total of 109 pairs were successfully matched using the propensity score matching method.The median length of hospital stay for LBW infants in the HAI group and non-HAI group were 34.0 and 11.0 days,respectively,the length of hospital extended 23 days in LBW infants in the HAI group(P＜0.001).The median hospitalization expenses for LBW infants in HAI group and non-HAI group were 38 067.6 and 12 375.7 Yuan,respectively,the hospitalization expense for LBW infants in HAI group was 25 691.9 Yuan more than non-HAI group(P＜0.001).The major increased expenses were examination,treatment and medication fees.The total hospitalization expenses in different birth weight LBW infants in HAI group were all higher than non-HAI group,and the differences were all statistically significant(all P＜0.05).LBW infants with gestational age＜32 weeks had longer length of hospital stay and higher total hospitalization expense,differences were all statistically significant(all P＜0.05).When the marginal profit ratios were 5％,10％,and 15％,respectively,the economic losses caused by HAI were 371 000 Yuan,742 000 Yuan,and 1 114 000 Yuan,respectively;The ratios of loss-profit and loss-profit to infection coefficient were 0.33 and 2.79,respectively.Conclusion HAI cause significant economic losses to both LBW infants and hospitals.Infants with a birth weight ≤1 000 g and those with a gestational age＜32 weeks are key populations for prevention and control.The lost-profit to infection coefficient can be used to estimate the economic loss of the hospital,timely adjust infection control measures,and reduce the incidence of HAI.

BACKGROUND/OBJECTIVES: This study aimed to examine the food security status of urban poor adolescents and its association with diet quality. SUBJECTS/METHODS: A cross-sectional survey was conducted among 188 adolescents aged 13–18 yrs living in Kuala Lumpur, Malaysia. Household food insecurity and dietary intake data were collected using the Radimer/Cornell hunger and food insecurity instrument and 2-day 24-h dietary recalls, respectively. Diet quality was determined using the Malaysian Healthy Eating Index (HEI). Weight and height were measured and body mass index-for-age, as well as height-for-age z scores were calculated. RESULTS: The present study revealed that 47.9% of the adolescents experienced household food insecurity, 24.5% experienced individual food insecurity, 18.6% household food security, and 9.0% child hunger. The mean score of diet quality was 56.83 ± 10.09, with a significantly lower HEI score among food insecure adolescents (household food insecure, individual food insecure, and child hunger) than household food secure adolescents (P = 0.001). The differences between food secure and food insecure households were found to be significant for energy (P = 0.001) and nutrients including proteins (P = 0.006), carbohydrates (P = 0.005), dietary fiber (P = 0.001), folate (P < 0.001), and vitamin C (P = 0.006). The multiple linear regression showed that adolescents who experienced food insecurity (β = −0.328; P = 0.003) were found to be significantly associated with poor diet quality (F = 2.726; P < 0.01), wherein 13.3% of the variation in the diet quality was explained by the food security status. CONCLUSIONS Experiencing food insecurity contributed to poor diet quality among urban poor adolescents. Further longitudinal studies are needed to comprehensively understand this association to improve food insecurity and diet quality among urban poor communities.

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen. METHODS: The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed. RESULTS: The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD^- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients. CONCLUSION The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD^- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.
Busulfan ; Cladribine ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Retrospective Studies ; Transplantation Conditioning