OBJECTIVE To investigate the biodistribution of lipid nanoparticles(LNPs)with different surface charges and different particle sizes in mice.METHODS LNPs were prepared using microfluidic technology by incorporating positively charged phospholipids,negatively charged phospholipids,ioniz-able phospholipids,and neutral phospholipids into the formulation to create LNPs with corresponding surface charges.The particle size of the LNPs was controlled by polyethylene glycol(PEG)modifica-tion and measured using dynamic light scattering(DLS)and transmission electron microscopy(TEM),while the surface charge was analyzed using a zeta potential analyzer.The LNPs were labeled with a fluorescent dye,and the mice were intravenously injected with 0.625 μmol·kg-1 of LNPs.At 1,4,12 and 24 h post-injection,the brain,heart,livers,spleen,lungs and kidneys were collected.The fluorescence distribution in different organs was detected using an in vivo imaging system to reflect the distribution of LNPs in various organs.RESULTS Particle size analysis showed that,except the ionizable lipid nanoparticles without PEG modification(LNP-MC3),which had a particle size>200 nm,the particle sizes of positively charged LNPs without PEG modification(LNP-Pos),PEG-modified positively charged LNPs(LNP-Pos-P),PEG-modified neutral LNPs(LNP-Neu-P),PEG-modified ionizable LNPs(LNP-MC3-P),and PEG-modified negatively charged LNPs(LNP-Neg-P)were all<200 nm.Zeta potential analysis revealed that the surface charges of the LNPs were the highest in LNP-Pos,followed by LNP-Pos-P,LNP-MC3-P,LNP-Neu-P,LNP-MC3 and LNP-Neg-P.In vivo imaging results indicated that LNP-Pos-P,LNP-Pos and LNP-MC3-P were primarily distributed in the livers,lungs and kidneys,respectively,while LNP-Neu-P and LNP-Neg-P in the livers,kidneys,and lungs,respectively.The distribution of LNP-MC3-P in the brain,heart,spleen and kidneys peaked at 12 h post-injection,but at 24 h in the livers.The distribution of LNP-Pos-P in the lungs peaked at 1 h post-injection.CONCLUSION LNPs are primarily distributed in the livers.Surface charges influence the second most highly-distributed organs.LNP-Pos-P and LNP-MC3-P are the second most highly-distributed in the lungs,and LNP-Neu-P and LNP-Neg-P in the kidneys.

OBJECTIVE To investigate the biodistribution of lipid nanoparticles(LNPs)with different surface charges and different particle sizes in mice.METHODS LNPs were prepared using microfluidic technology by incorporating positively charged phospholipids,negatively charged phospholipids,ioniz-able phospholipids,and neutral phospholipids into the formulation to create LNPs with corresponding surface charges.The particle size of the LNPs was controlled by polyethylene glycol(PEG)modifica-tion and measured using dynamic light scattering(DLS)and transmission electron microscopy(TEM),while the surface charge was analyzed using a zeta potential analyzer.The LNPs were labeled with a fluorescent dye,and the mice were intravenously injected with 0.625 μmol·kg-1 of LNPs.At 1,4,12 and 24 h post-injection,the brain,heart,livers,spleen,lungs and kidneys were collected.The fluorescence distribution in different organs was detected using an in vivo imaging system to reflect the distribution of LNPs in various organs.RESULTS Particle size analysis showed that,except the ionizable lipid nanoparticles without PEG modification(LNP-MC3),which had a particle size>200 nm,the particle sizes of positively charged LNPs without PEG modification(LNP-Pos),PEG-modified positively charged LNPs(LNP-Pos-P),PEG-modified neutral LNPs(LNP-Neu-P),PEG-modified ionizable LNPs(LNP-MC3-P),and PEG-modified negatively charged LNPs(LNP-Neg-P)were all<200 nm.Zeta potential analysis revealed that the surface charges of the LNPs were the highest in LNP-Pos,followed by LNP-Pos-P,LNP-MC3-P,LNP-Neu-P,LNP-MC3 and LNP-Neg-P.In vivo imaging results indicated that LNP-Pos-P,LNP-Pos and LNP-MC3-P were primarily distributed in the livers,lungs and kidneys,respectively,while LNP-Neu-P and LNP-Neg-P in the livers,kidneys,and lungs,respectively.The distribution of LNP-MC3-P in the brain,heart,spleen and kidneys peaked at 12 h post-injection,but at 24 h in the livers.The distribution of LNP-Pos-P in the lungs peaked at 1 h post-injection.CONCLUSION LNPs are primarily distributed in the livers.Surface charges influence the second most highly-distributed organs.LNP-Pos-P and LNP-MC3-P are the second most highly-distributed in the lungs,and LNP-Neu-P and LNP-Neg-P in the kidneys.

Objective To evaluate which factors may affect magnetic resonance imaging(MRI)performance in the detection of pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC).Methods This retrospective study involved 89 patients diagnosed with invasive breast carcinoma who received NAC at The Second Affiliated Hospital of Xi'an Jiaotong University from July 2019 to December 2021.Breast MRI was performed before and after NAC.Based on the pathological results obtained surgery after the completion NAC and using Miller-Payne classification as the evaluation standard,the patients were divided into two subgroups:pCR and non-pathological complete response(npCR).Chi-square test was used to compare the MRI characteristics of pre-NAC lesions between the two groups.ROC curve analysis was made to analyze the accuracy,sensitivity,specificity,positive predictive value,and negative predictive value of MRI after NAC;the diagnostic performance of MRI in predicting pCR in different tumor subtypes was analyzed.We made univariate and multivariate analyses of factors affecting radiographic complete response(rCR)and pCR concordance.Results MRI analysis after NAC showed rCR in 20 cases(22.5％)and pCR in 28 cases(31.5％).Considering rCR as a"positive"result of MRI analysis,MRI assessment was accurate in 79 cases,including 19 true positive cases and 60 true negative cases.MRI assessment was inaccurate in 10 cases,including 9 false negative cases and 1 false positive case.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MRI assessment of pCR were 67.86％,98.36％,88.76％,95.00％,and 86.96％.MRI had the lowest diagnostic efficiency in evaluating pCR of ERBB2+breast cancer after NAC.Single factor analysis showed that estrogen receptor(ER),clinical stage,background parenchymal enhancement,and maximum tumor diameter all affected the consistency of rCR and pCR(P＜0.05).Multivariate Logistic regression analysis showed that the independent influencing factor affecting the consistency of rCR and pCR was clinical stage.Conclusion MRI demonstrated good accuracy in predicting pCR after NAC in the breast cancer patients examined.Pre-treatment MRI characteristics and tumor subtypes may be related to the diagnostic accuracy of post-NAC MRI in breast cancer patients.

Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
Animals ; Mice ; Anticodon/genetics* ; Transcriptome ; Protein Biosynthesis ; RNA, Transfer/chemistry* ; Amino Acids/metabolism* ; Mammals/metabolism*

Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.

Objective:To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas (SPT) and non-metastatic SPT, and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods:Twelve metastatic SPT patients admitted to Peking University People's Hospital, Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively, including 3 males and 9 females, with a median age of 47 years old, ranging from 21 to 73 years old. Thirty non-metastatic SPT patients with clear diagnosis, clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group, including 12 males and 18 females, with a median age of 42 years old, ranging from 34 to 69 years old. Clinical data such as gender, age and pathological data were collected. Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results:There was no significant difference in general data between the two groups (all P>0.05). Among the 12 metastatic SPT patients, 4 cases metastasized to liver, 2 to spleen, 2 to lung, 2 to lymph nodes, 1 to mediastinum, and 1 to sacrum. Compared with the non-metastatic tissue, the MLH1 protein deletion in metastatic pancreatic lesions (metastatic SPT-P) and metastatic lesions (metastatic SPT-M) were increased [both 33.3%(4/12)], and the difference was statistically significant (both Chi square=5.00, both P=0.041). Compared with 0 (0/30) MLH1 gene methylation rate in non-metastatic SPT tissues, the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues [both 30% (3/10)] were higher, with statistical significance (both Chi square=0.96, both P=0.032). Conclusion:Compared with non-metastatic SPT, the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT. MLH1 methylation may occur before metastasis, which can be used as a predictor of SPT metastasis.

Objective:To study the use of primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck in pancreaticoduodenectomy (PD).Methods:The clinical data of 21 patients who were treated with primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck in PD at Beijing Chaoyang Hospital Affiliated, West Campus, Capital Medical University, Rizhao Hepatobiliary-pancreatic-splenic Surgery Research Institute, Binzhou Second People’s Hospital, Chaoyang Central Hospital from February 2022 to May 2022 were retrospectively analyzed. There were 12 males and 9 females, with ages ranging from 31.0 to 82.0 years (median age 63.0 years). The success rates of linear stapling at pancreatic neck, time of pancreaticojejunostomy, postoperative complications, pancreatic fistula risk score, and length of hospital stay were studied.Results:Among the 21 patients, there were 3 patients who underwent open PD and 18 patients who underwent laparoscopic PD. Primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck was successfully carried out in all these patients. The success rate was 100.0%. The success rate of finding pancreatic ducts at the pancreatic stumps and inserting an drainage tube was 100.0%(21/21). In the 3 patients who underwent open PD, the operation time were 230.0, 245.0 and 250.0 minutes respectively. The time for completing pancreaticojejunostomy were 12.0, 13.0 and 12.0 minutes respectively. The estimated blood loss were 300.0, 450.0 and 600.0 ml respectively. The length of hospital stay were 14.0, 15.0 and 21.0 days. In the 18 patients who underwent laparoscopic PD, the operation time was (295.9±14.5) min, the time for constructing pancreaticojejunostomy was (22.3±1.5) min, the blood loss was (180.0±40.0) ml, the length of hospital stay ranging from 8.0 to 16.0 days (median 10.5 days). Among all the 21 patients, the pancreatic fistula risk score was (4.7±1.5). Postoperative acute pancreatitis occurred in 3 patients (14.3%), delayed gastric emptying occurred in 4 patients (19.0%), and all of them recovered after conservative treatment. There was no postoperative bleeding, nosocomial infection, grade B and C postoperative pancreatic fistula or perioperative death.Conclusion:The continuous single-layer pancreaticojejunostomy after linear stapler closure of the pancreatic neck was safe, reliable, simple and technically easy. It has the potential to prevent clinical postoperative pancreatic fistula and pancreaticojejunostomy bleeding. It is worth to popularize this surgical procedure.

Mushroom-derived cyathane-type diterpenes possess unusual chemical skeleton and diverse bioactivities. To efficiently supply bioactive cyathanes for deep studies and explore their structural diversity,

Objective:To study the impact of Roux-en-Y reconstruction with isolated pancreatic drainage (RYR) on delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD).Methods:The data of 203 patients who underwent PD at 5 clinical centers from January 2014 to June 2020 were collected. According to the method of reconstruction of the digestive tract, the patients were divided into the RYR group ( n=88) and the conventional loop reconstruction (CLR) group ( n=115). The incidence and severity of DGE were compared between groups. The risk factors of clinically relevant DGE (CR-DGE) after PD were analysed by univariate and multivariate analyses. Results:Of 203 patients, there were 124 males and 79 females, aged (61.6±10.2) years. The overall incidence of DEG was 27.6% (56/203). The incidence of CR-DGE in the RYR group was significantly lower than that in the CLR group [13.6%(12/88) vs 26.1%(30/115), P=0.030]. Patient age of more than 65 years ( OR=2.966, 95% CI: 1.162-8.842, P=0.024), clinically relevant pancreatic fistula ( OR=3.041, 95% CI: 1.122-8.238, P=0.029), ascites and abdominal infection ( OR=10.000, 95% CI: 2.552-39.184, P=0.001), and CLR ( OR=3.206, 95% CI: 1.162-8.842, P=0.024) were identified as independent risk factors for CR-DGE. The duration of hospitalization and hospital expenditure of patients were significantly increased in the CR-DGE group ( P<0.05). Conclusions:Patients over 65 years with clinically relevant pancreatic fistula, with ascites or abdominal infection after operation, had a higher evidence of CR-DGE. Roux-en-Y reconstruction with isolated pancreatic could helped to decrease the incidence of CR-DGE after PD.

Objective:To explore the perivenous blocking management strategy for portal vein-superior mesenteric vein (PSMV) resection and reconstruction and its effect on postoperative complications in patients undergoing pancreaticoduodenectomy (PD).Methods:The data of 137 patients with pancreatic cancer treated with PD in Beijing Chaoyang Hospital Affiliated to Capital Medical University, Chaoyang Central Hospital, the Second Hospital of Chaoyang, Rizhao Central Hospital, the Second People's Hospital of Binzhou from January 2010 to December 2020 were collected. There were 83 males and 54 females with an average age of 61.8 years. There were 42 patients in the reconstruction group and 95 patients in the control group. The main intraoperative indexes and postoperative complications were compared between the two groups with the aim to review our experience in PSMV resection and reconstruction by using the perivenous blocking management strategy.Results:PD was successfully completed in 137 patients in the reconstruction group, the PSMV blocking time was 15-120 min, with a median of 30 min. The operation time 380 (330, 465) min, intraoperative blood loss 725 (500, 1000) ml, and postoperative hospital stay 21.0 (16.0, 28.0) d in the reconstruction group were significantly higher than those of control group [305 (280, 340) min, 400 (300, 500) ml and 18.0 (14.0, 24.5) d] (all P<0.05). The reoperation rate and perioperative mortality were 4.8% (2/42) and 2.4% (1/42) in the reconstruction group, while 2.1% (2/95) and 1.0% (1/95) in the control group, respectively. There was no significant difference between the two groups (both P>0.05). The incidence of pancreatic fistula, peritoneal effusion and infection, pulmonary infection of the reconstruction group was significantly higher than those of the control group ( P<0.05). There was no significant difference in the incidence of postoperative bleeding, delayed gastric emptying, biliary fistula, incision infection, reoperation between the two groups ( P>0.05). Conclusions:PSMV resection and reconstruction significantly increased the incidences of complication after PD, including pancreatic fistula, peritoneal effusion/infection and pulmonary infection. The perivenous blocking management strategy significantly promoted smooth postoperative recovery and effectively reduced morbidity rates of postoperative bleeding and mortality after PSMV resection and reconstruction in PD.