With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes

Objectives:The purpose of this cross-sectional study was to determine the predictive value of measuring awake blood pressure(BP)at different time points on nocturnal hypertension by ambulatory blood pressure monitoring(ABPM)device in patients with hypertension. Methods:A total of 204 consecutive hypertensive outpatients seeking medical care at the First Affiliated Hospital of Fujian Medical University from April 2023 to July 2023 were enrolled.We measured office BP and out-office BP.Out-office BP include evening BP,bedtime BP,morning BP and mean morning BP which were measured by ABPM device and BP daily record.Nocturnal hypertension was defined by the mean nocturnal systolic blood pressure≥120 mmHg(1 mmHg=0.133 kPa).ROC curve analyses of different awake blood pressure was established to identify significant correlates to nocturnal hypertension.The serial test was also performed.The value of the two indexes in predicting nocturnal hypertension was compared.The predictors of nocturnal hypertension were evaluated by multivariate analysis. Results:Of the 204 subjects,104(51.0%)had nocturnal hypertension.The repeated measures analysis of variance(ANOVA)showed that mean nighttime systolic BP and bedtime systolic BP were similar(P=0.641).Nocturnal hypertension was present in 75.7%(84/111)of patients with bedtime systolic BP≥120 mmHg,in 94.2%(49/52)of patients with bedtime systolic BP≥135 mmHg and in 88.2%(75/85)of patients with mean morning systolic BP≥135 mmHg.ROC curve analyses showed that the diagnostic accuracy of mean morning systolic BP(AUC 0.903,P＜0.05)for subjects with nocturnal hypertension was significantly superior to that of office systolic BP,evening systolic BP,bedtime systolic BP,morning systolic BP.Multivariate logistic regression analysis revealed that mean morning systolic BP and bedtime systolic BP were significantly associated with a higher risk of nocturnal hypertension(P＜0.05).ROC curve analyses of predicted probability of bedtime systolic BP and mean morning systolic BP showed higher diagnostic accuracy(AUC 0.929,P＜0.05).The serial test showed that nocturnal hypertension was present in 98.0%(49/50)of patients with bedtime systolic BP≥130 mmHg and mean morning systolic BP≥135 mmHg. Conclusions:Mean morning BP and bedtime BP are significant correlates of nocturnal hypertension in patients with hypertension,and combined mean morning BP with bedtime BP showed higher diagnostic accuracy,which might used for predicting nocturnal hypertension with high efficiency.

Allogeneic hematopoietic stem cell transplantation is an effective method for treating various hematological diseases. Membranous nephropathy is the second leading cause of novo glomerular disease after transplantation. Protocadherin FAT1 is a target antigen for diagnosing membranous nephropathy, primarily related to hematopoietic stem cell transplantation. Here we report a rare case of membranous nephropathy after hematopoietic stem cell transplantation. The target antigen of membranous nephropathy was confirmed to be FAT1 by pathology combined with mass spectrometry analysis. The nephrotic syndrome achieved partial remission after corticosteroid combined with cyclosporine treatment, and the patient's condition was stable during follow-up.

OBJECTIVE To study the spectru m-toxicity relationship of in vitro hepatotoxicity of aqueous extract from Euodia rutaecarpa. METHODS The aqueous extract from 16 batches of E. rutaecarpa from different habitats were prepared. The fingerprints of aqueous extract from E. rutaecarpa were established by ultra high performance liquid chromatography （UPLC） method and Similarity Evaluation System of TCM Fingerprint （2012A edition ），and common peaks were identified and the similarity was evaluated. Using normal human hepatocytes L 02 as subject ，inhibitory effect of aqueous extract from 16 batches of E. rutaecarpa to them were investigated. The spectrum-toxicity relationship of UPLC fingerprint of aqueous extract from E. rutaecarpa with the hepatotoxicity of hepatocytes L 02 was analyzed by grey relational analysis （GRA）and partial least squares regression analysis （PLSR）. The corresponding compound of the chromatographic peak with the greatest correlation with the in vitro hepatotoxicity of E. rutaecarpa were isolated ，prepared and identified. RESULTS There were 27 common peaks in UPLC fingerprints of aqueous extract from 16 batches of E. rutaecarpa ，with similarity of 0.375-0.995. Totally 9 peaks were confirmed ，i.e. neochlorogenic acid （peak 5），chlorogenic acid （peak 9），cryptochlorogenic acid （peak 10），caffeic acid （peak 12），rutin （peak 16），hyperin（peak 17），dehydroevotarine（peak 19），evotarine（peak 24），rutecarpine（peak 25）. The aqueous extract from 16 batches of E. rutaecarpa showed significant inhibitory effect on the growth of L 02 cells（P＜0.05 or P＜0.01），and the inhibitory rate ranged from 6.68％ to 67.95％. GRA showed that there were 18 common peaks with correlation degree greater than 0.8，which were peak 8＞peak 3＞peak 23＞peak 7＞peak 4＞peak 9＞peak 12＞peak 2＞peak 19＞peak 6＞ 4928381。E-mail：799247687@qq.com peak 15＞peak 5＞peak 1＞peak 17＞peak 21＞peak 26＞ peak 20＞peak 14 in descending order of correlation degree. PLSR showed that there were 14 peaks with regression coefficient＞0 and variable importance projection value ＞1，and the order of regression coefficient was peak 8＞peak 3＞peak 23＞ peak 2＞peak 7＞peak 4＞peak 12＞peak 9＞peak 19＞peak 5＞peak 17＞peak 26＞peak 10＞peak 15. Peak 8 had the greatest correlation with in vitro hepatotoxicity，and the corresponding compound of this peak was identified as 6-O-trans caffeoyl gluconic acid. CONCLUSIONS The in vitro hepatotoxicity of aqueous extract from E. rutaecarpa is the result of multiple component interaction，among which 6-O-trans caffeoyl gluconic acid shows closest relation with in vitro hepatotoxicity.

Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.

Objective:To evaluate the value of controlled low central venous pressure (CLCVP) in laparoscopic hepatectomy within an enhanced recovery after surgery (ERAS) programme.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, of liver function Child-Pugh grade A, with New York Heart Association classⅠor Ⅱ, scheduled for elective laparoscopic hepatectomy with an expected surgery time 3-5 h, were divided into 2 groups ( n=30 each) using a random number table method: CLCVP-ERAS group (group CE) and routine ERAS group (group E). In group CE, the central venous pressure was maintained less than 5 cmH 2O through using restricted fluid replacement, adjusting the position, giving the vasodilator and etc.In group E, the central venous pressure was maintained at 5-12 cmH 2O.Arterial blood samples were then collected before operation and at 1 and 4 days after operation for determination of parameters of hepatic and renal functions.The volume of fluid infused before and after liver resection, total volume of intraoperative fluid infused, blood loss, blood transfusion, duration of surgery, postoperative time to first flatus, off-bed time, length of hospitalization and total cost of hospitalization were recorded. Results:Compared with group E, the volume of fluid infused before liver resection, total volume of intraoperative fluid infused, blood loss, and blood transfusion were significantly decreased, the volume of fluid infused after liver resection was increased, the duration of surgery, time to first flatus after operation, off-bed time and length of hospitalization were shortened, and the total cost of hospitalization was reduced ( P<0.05), and no significant change was found in the parameters of hepatic and renal functions in group CE ( P>0.05). Conclusion:CLCVP is helpful for the rapid recovery of patients without obvious adverse reactions when used for laparoscopic hepatectomy within an ERAS programme.

OBJECTIVE: To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies. METHODS: A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks. RESULTS: A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ=11.345, χ=10.160, χ=6.358; all < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ=6.813, =0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation. CONCLUSIONS Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.
Antiviral Agents ; Carcinoma, Hepatocellular ; etiology ; DNA, Viral ; Follow-Up Studies ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; complications ; Liver Neoplasms ; etiology ; Prospective Studies

Objective:To investigate the effects of Jianpijiedutang combined with Kangfuxin Liquid in the treatment of recurrent oral ulcer(ROU).Methods:80 patients with ROU were divided into 2 groups(n=40).The patients in control group were treated with Kangfuxin Liquid local spray,those in the test group were treated with Jianpijiedutang combined with Kangfuxin Liquid spray.The patients were followed up for 24 weeks.The effects were evaluated according to the trial standard of Chinese Stomatological Association.Results:The interval of ROU increased and ulcer number decreased in the 2 groups during the observation period,the test group showed more effective outcome than the control group(P<0.05).In the treatment group ROU interval increased more than in the control group(P<0.01),and ROU ulcer number decreased more(P<0.01).Conclusion:The Jianpijiedutang combined with Kangfuxin Liquid spray is more effective than the latter used only.

Objective To investigate the value of aortic dissection detection (ADD) risk score in the diagnosis of acute aortic syndromes (AAS). Methods Three hundred and forty-two patients with acute chest pain or back pain admitted to the Department of Emergency of the First Affiliated Hospital of Xiamen University from January 2013 to April 2016 were enrolled. At last, 71 patients were definitely diagnosed as AAS (AAS group), and 271 cases were diagnosed as non-AAS (non-AAS group). Furthermore, according to the ADD risk score, they were subdivided into two groups: low-risk (ADD score ≤ 1) and high risk (ADD score >1) subgroups. In the two groups, the ADD risk indexes and the proportions of patients with different risk scores were observed; the receiver operating characteristic curve (ROC curve) was drawn to evaluate the value of ADD risk score for diagnosing AAS. Results Compared with the non-AAS group, the proportions of patients in AAS group with indicators of high-risk pain characteristics, such as sudden pain and laceration-like pain were increased significantly [83.1% (59/71) vs. 31.0% (84/271), 29.6% (21/71) vs. 0 (0/271)];meanwhile, the proportions of patients with high-risk physical examination indicators, such as systolic blood pressure differences among the 4 extremities and the defect of local nerve function in AAS group were also significantly increased [23.9% (17/71) vs. 0 (0/271), 11.3% (8/71) vs. 0 (0/271), both P < 0.05]; the proportion of patients with high risk AAS score in AAS group was higher than that in the non-AAS group [66.2% (47/71) vs. 1.5% (4/271), P < 0.01]. The sensitivity of ADD score ≥ 1 for diagnosis of AAS and area under ROC curve (AUC) were all higher than those of ADD score ≥2 (sensitivity: 98.6% vs. 66.2%, AUC: 0.819 vs. 0.564), moreover, the specificity and the positive predictive value of ADD score ≥ 2 for diagnosis of AAS were higher than those of ADD score ≥ 1 (98.5% vs. 59.8%, 92.2% vs. 39.1%respectively). When the ADD risk score ≥ 1, its odds ratio (OR) = 104.0, 95% confidence interval (CI) was 0.761-0.877, P = 0.000; while ADD risk score ≥ 2, OR = 130.7, 95%CI was 0.516-0.612, P = 0.003. Conclusion It is shown that when ADD risk score (> 1) is used to diagnose AAS, it has relatively high sensitivity, when ADD score being high risk (> 1 score) is applied to diagnose AAS, its specificity is high, thus ADD risk score has important value in helping the early diagnosis of AAS.

We studied the status of parasite pollution in fish and shrimps in Fujian Province,and provided basis for prevention and control of parasite pollution and food safety in aquatic products.Stratified random sampling method was used,and Fujian Province was divide into Eastern,Southern,Western,Northern and Central five regions of Fujian province.Based on the data collected from the five regions between 2012 and 2016,digestion and compression methods were conducted to detect the levels of parasite metacercariae and larvae in both freshwater and marine products.Results showed that the total parasitoid infection rate was 5.15％ (130/2 524).The infection rate of trematode metacercariae and nematode larvae were 3.72％ (94/2524) and 1.43％ (36/2 524),respectively.Twenty-eight marine aquatic species were investigated and the infection rate was 17.25 ％ (88/510),in the form of Anisakis infection.The parasite infection rates in the five regions were 10.38％ (27/260) in Mindong,5.84％ (27/462) inMinnan,4.63％ (30/648) in Minxi,4.64％ (29/625) in Minbei and 9.91％ (103/1 039) in Minzhong.The freshwater products in Fujian Province have been polluted by parasites and are area-depended.The infection rate of marine aquatic products is kept in a high level.Fujian Province should strengthen the food safety and health publicity,take effective prevention and control strategies,and use early warning mechanisms to insure the food safety in province.