Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (-25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.
Aged ; Aged, 80 and over ; Atrioventricular Block/therapy* ; Bundle of His/physiology* ; Cardiac Pacing, Artificial ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Molecular pharmacognosy( MP) is a new interdisciplinary science,which integrates the pharmacognosy and molecular biology,and focuses on the crude drugs' classification and identification,cultivation and protection,and production of active ingredients at the molecular level. Pogostemon cablin is one of the ten major southern medicines in China,MP research on this famous herb has developed on the basis of traditional research methods,and achieved certain results. This article summarized the MP research achievements of P. cablin in recent years,the prospect of this field is also discussed to provide references for the protection,development and utilization of P. cablin resources.
China ; Lamiaceae ; Molecular Biology ; Pharmacognosy ; Pogostemon

AIM:To analyze zebrafish embryos and to identify erythropoietin (Epo) as an active renal anti-apoptotic factor in an Epo receptor (EpoR)-dependent manner. METHODS:For transient knockdown of Epo and EpoR in renal Tg (wt1b:EGFP) zebrafish reporter lines, the morpholino antisense oligonucleotide technique was used. Morphant zebrafish embryos were phenotypically analyzed using fluorescence microscopy. Apoptosis was determined by TUNEL assay and Annexin V staining. Western blot was used to identify Akt phosphorylation in Epo and EpoR knockdown zebrafish. RE-SULTS:Epo and EpoR zebrafish morphants exhibited pathophysiological changes within the pronephros, adversely affecting pronephric structure. Zebrafish embryos upon silencing of Epoa and EpoR showed a significant increase in the apoptosis within the zebrafish pronephros, consequently leading to renal pathophysiological effects. Decreased p-Akt was identified in Epo and EpoR knockdown zebrafish embryos. CONCLUSION:Epo is an essential regulator of renal development and function by interacting with its receptor EpoR and thereby repressing apoptosis, mechanistically by promoting Akt phospho-rylation.

To investigate the space-time patterns of schistosomiasis after the stage of transmission controlled in Hubei Province, so as to provide the reference for precise controlling.The data of human schistosomiasis cases in Hubei Province from 2015 to 2016 and basic information of human schistosomiasis cases and serum antibody titer of human schistosomiasis cases in 2016 were collected and analyzed. The spatial clustering of human schistosomiasis was detected by the Flexible spatial scan statistics and Kulldorff circular scan statistic, respectively.Totally 64 819 serological positive cases from 51 counties and 1 504 stool hatching positive cases from 17 endemic counties were reported in Hubei Province in 2015, and 39 365 serological positive cases were reported from 48 counties in 2016. All of them were identified as the research objects. No stool hatching positive cases were reported from the routine work in the whole province in 2016. There were 1 603 cases of the highest antibody titer (1∶80 or more), with the proportion of 4.07%. According to the results of Kulldorff spatial clustering analysis, there were eight and six spatial clustering areas in the distribution of serological positive cases and stool hatching positive cases in 2015, respectively. The numbers of spatial clustering areas in the distribution of serological positive cases and the cases of the highest antibody titer (1∶80 or more) were eight and five in 2016, respectively. According to the results of Flexible spatial clustering analysis, there were three and two spatial clustering areas in the distribution of serological positive cases and stool hatching positive cases in 2015, respectively. The numbers of spatial clustering areas in the distribution of serological positive cases and the cases of highest antibody titer (1∶80 or more) were two and one in 2016, respectively.The distribution of human schistosomiasis cases is not balanced, and there is spatial clustering in Hubei Province. So the key area for prevention and control is on the middle and lower reaches of the Yangtze River in the future.

The role of (pro)rennin receptor (PRR) in cardiomyocytes of a heart failure (HF) rat model was studied. Spontaneously hypertensive rats (SHR) with HF (SHR-HF) or not were identified by two-dimensional (2-D) ultrasound. Age-matched Wistar Kyoto normotensive (WKY) rats were used as controls. PRR short hair RNA (sh-RNA) was injected into the heart of SHR-HF. Simultaneously SHR and controls received the same shRNA injection into the heart. Scramble shRNA was injected into the heart as controls. The expression of PRR mRNA and protein in cardiomyocytes was detected by using real-time PCR and Western blotting respectively. The heart function was evaluated by 2-D ultrasound, including eject fraction (EF%), fractional shortening (FS%), left ventricle thickness (LV), and inter-ventricular septal thickness (IVS). The number of apoptotic cardiomyocytes was counted by using flow cytometry. The results showed that the mRNA and protein expression levels of PRR were significantly higher in cardiomyocytes of SHR-HF group than in those of SHR group or control group. The apoptosis of myocytes in SHR-HF group was increased as compared with SHR group or control group. After knock-down of PRR with shRNA in SHR-HF group, the apoptosis of myocytes was reduced, resulting in the improved heart function. It was suggested that down-regulation of PRR might protect the heart from development of HF in SHR-HF by inhibiting the apoptosis of cardiomyocytes.
Animals ; Apoptosis ; genetics ; physiology ; Blotting, Western ; Chymosin ; metabolism ; Disease Models, Animal ; Enzyme Precursors ; metabolism ; Gene Expression ; Heart Failure ; genetics ; metabolism ; physiopathology ; Male ; Myocardium ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; RNA Interference ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptors, Cell Surface ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo analyze the high risk factors for tumor recurrence in short term after hepatectomy for the patients with primary hepatocellular carcinoma (HCC).

METHODSFive hundreds and two patients with primary HCC underwent hepatectomy were included from January 1997 to December 2008. Among these patients, males were 419 cases and females were 83 cases. The age was 14 to 82 years (average age 54 years). The results of evaluation on 2 months after resection and tumor recurrence and survival were analyzed.

RESULTSAccording to the operative and pathologic findings and the evaluation on 2 months after hepatectomy, the patients with vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher after resection or(and) positive TACE (tumor dyeing on TACE within 1 month and a deposit of lipiodol on CT scan) were high risk factors (high-risk group, 106 cases, 21.1%), the recurrence-free survival was 22%, 9% and 3% (1, 2 and 5 year) and overall survival was 52%, 25% and 8%. On the non-high risk group patients, the recurrence-free survival was 84%, 67%, 42% and 31% (1, 2, and 5 year) and overall survival was 97%, 85%, 56% and 35%. The bigger tumor, poor differentiation, tumor invading to liver capsule, satellite focus and TNM III-IV stage in high-risk groups were more significantly than that in non-high-risk groups.

CONCLUSIONThe vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher or (and) positive TACE within 2 months after resection are high risk factors for HCC patients in short term after hepatectomy, which mean tumor remnant.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Disease-Free Survival ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; mortality ; pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVETo investigate the effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene (Ad(5)-HGF) on hematopoietic stem cells mobilization in patients with extensive coronary heart disease.

METHODSPatients with extensive coronary heart disease were treated with intracoronary infusion of adenovirus vector encoding hepatocyte growth factor (Ad(5)-HGF 5 x 10(9) pfu) gene plus stent implantation (n = 9) or equal physiological saline plus stent implantation (n = 9). Angioplasty and stent implantation was performed according to standard clinical practice by the femoral approach and blood samples were drawn from each patient at baseline before PCI, 6 to 24 hours and 6 days post procedure. The number of CD34(+), CD38(+) and CD117(+) cells in peripheral blood was analyzed by flow cytometer.

RESULTSThe number of circulating CD34(+) cells in Ad(5)-HGF gene treatment group 6 hours after procedure and the number of circulating CD117(+) cells 6 days post procedure were significantly higher in Ad(5)-HGF gene treatment group than those in the control group (0.104 +/- 0.082 vs. 0.022 +/- 0.012, P = 0.021) and (0.058 +/- 0.058 vs. 0.012 +/- 0.009, P = 0.034), respectively.

CONCLUSIONIntracoronary administration of Ad(5)-HGF could mobilize hematopoietic stem cells into peripheral blood and the consequent role of this observation on myocardial regeneration warrants further detailed studies.

Adenoviridae ; genetics ; Aged ; Coronary Disease ; blood ; Female ; Genetic Therapy ; Genetic Vectors ; Hematopoietic Stem Cell Mobilization ; methods ; Hepatocyte Growth Factor ; genetics ; therapeutic use ; Humans ; Male ; Middle Aged ; Transfection

Adenovirus vectors are one of the most promising gene transfer systems. They are of great value for gene therapy because these vectors achieve temporal high-level transgene expression and high gene transfer efficiency. To meet increasing needs of adenovirus vectors for gene therapy programs, parallel development of efficient, scalable and reproducible production processes is required. Perfusion cultivation of 293 cells is one of the most commonly used methods to produce adenovirus vectors and it is suitable for industrialized production specially. Experimental studies had been carried out to produce recombinant adenovirus containing the green fluorescent protein gene (Ad-GFP) by perfusion cultivation of HEK-293 N3S cells in a 5L stirring bioreactors. Perfusion rate was 1-2 volume/day. To infect the 293 N3S cells with Ad-GFP at the density of (2-4) x 10(6) cells/ ml. The time of collecting cells was 48 hours post infection. After three rounds of freeze/thaw and centrifugation, the crude viral lysates were stored at--80 degrees C until use. Then to get the Ad-GFP products by 2 x CsCl-gradient purification. The purity of the products was determined by the A260/A280 ratio and a high performance liquid chromatography (HPLC) assay. The infective titer was determined by a TCID50 assay. The culture term was 10-12 days. The infectious titer, the number of virus particle and the ratio of infectious titer to virus particle for the product were 1.0 x 10(11) IU/mL, 1.68 x 10(12) VP/mL and 6.0% IU/VP respectively. The A260/A280 ratio was 1.33, and the purity determined by HPLC was 99.2%. The cell specific productivity was around 1000 IU/cell. By perfusion cultivation of 293 N3S cells in a 5L stirring bioreactors, we established the production process for Ad-GFP, which paves a way to produce other recombinant adenovirus for gene therapy.
Adenoviridae ; genetics ; growth & development ; isolation & purification ; Bioreactors ; microbiology ; Cell Line ; Gene Transfer Techniques ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Humans ; Kidney ; cytology ; virology ; Recombinant Proteins ; biosynthesis ; genetics ; Recombination, Genetic ; Virus Cultivation ; instrumentation ; methods

OBJECTIVETo evaluate the significance of gastric acid reflux in children with reflux esophagitis (RE).

METHODSTwenty-four-hour esophageal pH monitoring and gastroscopy were performed in 180 children suffered from vomiting. The relationship between RE, non-esophagitis (NE), non-erosive reflux disease (NERD) and gastroesophageal reflux (GER) was analyzed.

RESULTSSixty-five of the 180 patients were confirmed as having RE by endoscopy. Among them, the number of cases with grades I, II and III RE according to the diagnostic criteria by endoscopy was 37, 19 and 9 cases, respectively, while the other 115 cases were diagnosed as NE. The positive rate of acid reflux in RE group was 58.5% (38/65), while it was 42.6% (49/115) in NE group (chi(2) = 4.179, P < 0.05). All parameters of acid reflux in RE group except for the episode of reflux and the number of reflux longer than 5 min were significantly higher than those in NE group. None of the parameters of acid reflux except for Boix-Ochoa score in grade III RE patients was significantly higher than that in both grade II and grade I RE cases. However, the difference in acid reflux parameter between grade I and grade II RE patients had not reached statistical significance. The results also showed that the positive rate of pathological acid reflux was 48.3% (87/180). Among them, 38 cases were RE, while other 49 cases were NERD. The difference in acid reflux between these two groups was not significant.

CONCLUSIONSGastric acid reflux may play a major role in the development of RE in children, but may not be a sole pathogenic factor. The degree of acid reflux is not closely correspondent to the severity of RE. Acid reflux may not completely contribute to RE. Gastroscopy is very important for patients with reflux symptom.

Adolescent ; Child ; Child, Preschool ; China ; Esophageal pH Monitoring ; Esophagitis, Peptic ; diagnosis ; etiology ; pathology ; physiopathology ; Esophagoscopy ; Female ; Gastric Acid ; secretion ; Gastroesophageal Reflux ; complications ; Humans ; Hydrogen-Ion Concentration ; Infant ; Male ; Severity of Illness Index