This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Aim To study the molecular mechanism of pterostilbene(PTS)inhibiting the growth of esophage-al squamous cell carcinoma(ESCC).Methods Soft agar assay was used to detect the effect of PTS on the anchored independent growth of KYSE150.TMT-la-beled quantitative proteomics analysis was used to ana-lyze the influence of PTS on the proteome of KYSE150.Then the differentially expressed proteins(DEPs)enrichment was analyzed by GO and KEGG,and signaling pathway interactions were analyzed by STRING database.The molecular docking model of PTS and PPARα was established by computer.Trans-mission electron microscopy was used to observe the in-fluence of PTS on the morphology change of KYSE150.Western blot analysis the effects of PTS on PPARα sig-naling pathway and ferroptosis related proteins expres-sion.Results PTS inhibited the anchorage-independ-ent growth capability of KYSE150.A total of 249 DEPs were identified by proteomic analysis,including 175 up-regulated proteins and 74 down-regulated pro-teins.The DEPs enrichment analysis showed that PPAR signaling pathway was related to unsaturated fat-ty acid synthesis,pyruvate metabolism and other meta-bolic signaling pathways.PTS caused the reduction of mitochondrial volume and mitochondrial cristae of KYSE150.PTS inhibited the expression of PPARα sig-naling pathway and ferroptosis related proteins.Con-clusion PTS induced the ferroptosis of ESCC by in-hibiting PPARα signaling pathway.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Acute mitral regurgitation(MR)in the setting of myocardial infarction(MI)may be the result of papillary muscle rupture(PMR).The clinical presentation can be catastrophic,with refractory cardiogenic shock.This condition is associated with high morbidity and mortality.Transcatheter edge-to-edge repair(TEER)has become increasingly common in treating severe mitral regurgitation.This case details a successful TEER is feasible and safe in patients with acute MR following MI.TEER is an emerging treatment option in this clinical scenario that should be taken into consideration.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*