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.

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.

Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable sig-nificance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39％of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.

Objective: To evaluate the safety and clinical efficiency of holmium laser enucleation of the prostate (HoLEP) in the treatment of small-volume BPH (SBPH) complicated by severe lower urinary tract symptoms (LUTS). METHODS: We retrospectively analyzed the clinical data on 82 cases of SBPH with severe LUTS treated by HoLEP from January 2017 to December 2018. The patients were aged (65.5 ± 7.6) years, with a mean prostate volume of <40 ml, a total IPSS of 24.8 ± 4.6, a QOL score of 5.2 ± 0.8, the maximum urinary flow rate (Qmax) of (7.6 ± 3.7) ml/s, and a mean PSA level of (1.8 ± 1.4) μg/L. RESULTS: All the operations were successfully completed, the mean operation time averaging (30.2 ± 5.0) min, enucleation time (26.7 ± 5.6) min and comminution time (3.5 ± 1.1) min, and the enucleated tissue weighing (20.3 ± 4.9) g. After surgery, the bladders were irrigated for (3.5 ± 1.9) h, with (3.0 ± 1.7) L of rinse solution, and catheterization lasted (24.8 ± 9.7) h. Histopathology revealed moderate or severe lymphocytic infiltration in 69 cases (84.1%). At 6 months after operation, significant improvement was observed in the IPSS, QOL, Qmax and PSA level compared with the baseline (P < 0.05). To date, no urethral stricture-related reoperation was ever necessitated. CONCLUSIONS HoLEP is safe and effective for the treatment of SBPH complicated by severe LUTS and can be employed after adequate preoperative evaluation of the patient.《.
Humans ; Lasers, Solid-State ; Lower Urinary Tract Symptoms/surgery* ; Male ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Retrospective Studies

【Objective】 To investigate the molecular mechanism of PES1 promoting the proliferation, invasion and migration of papillary thyroid cancer by upregulating the ERα/ERβ protein ratio. 【Methods】 The protein expression level of PES1, ERα, and ERβ in normal thyroid tissue specimens and PTC tissue specimens were analyzed by immunohistochemistry. We preformed Western blotting to detect the expression of PES1, ERα and ERβ using human PTC-derived BCPAP and K1 cells and normal thyroid-derived Nthy-ori3-1 cells. In Nthy-ori3-1 and BCPAP cells, Western blot was used to detect the effect of PES1 overexpression and PES1 knockdown on the ratio of ERα and ERβ protein expression. MTT and Transwell were used to measure the effect of PES1, ERα and ERβ on the proliferation, invasion and migration of PTC cells. 【Results】 The protein expression level of PES1 and ERα in PTC tissues was significantly higher than that in normal adjacent tissues, while the protein expression level of ERβ was significantly lower than that in normal adjacent tissues. PES1 and ERα protein levels were gradually increased and ERβ protein level was decreased with the degree of malignant behavior of PTC patients. And PTC patients with large tumor size, ETE, LNM, high BRAFV600E expression and high TNM stage(III-IV) had higher rates of high PES1 and ERα protein expression and low ERβ protein expression. In Nthyori3-1 cells ERα/ERβ protein ratio was significantly less than 1(about 0.43), however, in BCPAP and K1 cells ERα/ ERβ protein ratio was significantly greater than 1(about 2.25, about 2.82). The protein expression level of PES1 was positively correlated with the protein ratio of ERα/ERβ. The overexpression of PES1 made a significant increase of ERα/ERβ protein ratio in Nthy-ori3-1 cells(about 2.54). The down-regulation of PES1 significantly reduced ERα/ERβ protein ratio in BCPAP cells(about 0.41). The down-regulation of PES1 decreased the proliferation, invasion and migration of papillary thyroid carcinoma cells, while the overexpression of PES1 significantly enhanced the proliferation, invasion and migration of papillary thyroid carcinoma cells. 【Conclusions】 ERα and ERβ are co-expressed in human PTC tissues and cells. PES1 modulates the balance between ERα and ERβ by elevating the ERα protein level and simultaneously reducing the ERβ protein level, then up-regulating the ERα/ERβ protein ratio and promoting the proliferation, invasion and migration of PTC cells, and then promoting the occurrence and development of PTC.

BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

OBJECTIVE: To investigate the effect of electroacupuncture preconditioning combined with induced urination on urinary retention after milligan-morgan hemorrhoidectomy. METHODS: Eighty patients with mixed hemorrhoids were randomly divided into an electroacupuncture group and a routine group, 40 cases in each group. Anesthesia at Yaoshu (GV 2) was given in the two groups. In the electroacupuncture group, electroacupuncture at Zhongji (CV 3)，Guanyuan (CV 4)，Pangguangshu (BL 28) and Sanyinjiao (SP 6) was applied with tolerant intensity for 30 min before operation, 2 Hz/100 Hz in frequency. After operation, induced urination was given, namely hot compress of bladder area and sound of hearing water. In the routine group，induced urination was given after operation. The score of the first urination waiting time, the distension of lower abdomen on the evening of the postoperative, the first time urinary volume and incidence of urinary retention were compared between the two groups. RESULTS: The scores of the first urination waiting time after operation and distension of lower abdomen in the evening of the postoperative in the electroacupuncture group were lower than those in the routine group, the first time urinary volume was more than that in the routine group, and the incidence of urinary retention was lower than that in the routine group (5.0% (2/40) vs 22.5% (9/40), all <0.05). CONCLUSION Electroacupuncture preconditioning combined with induced urination can effectively prevent the incidence of urinary retention after milligan-morgan hemorrhoidectomy.
Electroacupuncture ; Hemorrhoidectomy ; Hemorrhoids ; Humans ; Urinary Retention ; therapy ; Urination

OBJECTIVE: To compare the effect of electroacupuncture preconditioning with different frequencies on anal pain after milligan-morgan hemorrhoidectomy. METHODS: A total of 120 patients with mixed hemorrhoids were randomly divided into an electroacupuncture group A (dilatational wave, 2 Hz/100 Hz in frequency), an electroacupuncture group B (continuous wave, 2 Hz in frequency) and an electroacupuncture group C (continuous wave, 100 Hz in frequency), 40 cases in each group. Electroacupuncture at Xialiao (BL 34) and Chengshan (BL 57) was applied with tolerant intensity for 30 min before operation in all groups. The number of additional anesthetic drugs in the 3 groups, the visual anal pain score (VAS) and limb activity score at 4, 12, and 24 h after operation, the maximum VAS score within 24 h after surgery and oral dose of aminophenol dihydrocodeine were compared. RESULTS: The number of additional anesthetic drugs in the electroacupuncture group A, the electroacupuncture group B and the electroacupuncture group C were 4, 5, 4 respectively, and there was not statistically significant (>0.05). There was no significant difference in the anal pain VAS score and limb activity score at 4 h after operation among the 3 groups (>0.05), at the 12 h after operation, the VAS scores and limb activity scores in the electroacupunctures group A and B were lower than those in the electroacupuncture group C (<0.05), at 24 h after operation, the VAS score and limb activity score in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (<0.05), the maximum VAS score within 24 h and oral dose of aminophenol dihydrocodeine within 24 h after operation in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (<0.05). CONCLUSION Different frequency electroacupuncture preconditioning has the effect of alleviating anal pain after milligan-morgan hemorrhoidectomy. The analgesic effect of electroacupuncture with different frequencies is different. The electroacupuncture analgesic effect of 2 Hz /100 Hz dilatational wave is better than 2 Hz and 100 Hz continuous waves.
Anal Canal ; Electroacupuncture ; Hemorrhoidectomy ; Hemorrhoids ; therapy ; Humans ; Pelvic Pain

Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion: Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.
Antineoplastic Agents ; Dasatinib/therapeutic use* ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors ; Retrospective Studies ; Treatment Outcome

Objective To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase(LTC4S) during hepatic ischemia reperfusion(I/R).Methods Adult male SD rats were divided into 3 groups:control group(sham),ischemic-reperfusion group(I/R) and V-PYRRO/NO group. Liver subjected to 1 hour of partial hepatic ischemia followed by 5 hours of reperfusion, saline or V-PYRRO/NO[1.06 mmol/(kg·h)] administered intravenously. The mRNA expression of LTC4S in rat liver was examined by RT-PCR method,the protein expressions of NF-κB p65,p50 and IκB in liver cell lysates and nu-clear extracts were detected by Western blot analysis. Results Hepatic mRNA expression of LTC4S in I/R group was higher than that in sham group(P<0.05), whereas it was lower in V-PYRRO/NO group than that in I/R group(P<0.05). Moreover,compared with sham group,the protein expressions of NF-κB p65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm(P<0.01,P<0.05) during hepatic I/R injury.However,IκB protein in three groups did not change. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was found in sham liver,I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65,but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions V-PYRRO/NO may down-regulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB during hepatic I/R injury.