Messenger ribonucleic acid (mRNA) is a promising therapeutic drug with great potential in the fields of immunology, oncology, vaccines and inborn metabolic diseases. However, due to its instability and susceptibility to nuclease degradation, efficient delivery vectors are required. Lipid nanoparticles (LNPs) are recognized as the most mature delivery vectors due to their advantages of easy formulation, high stability, efficient cell uptake and endosomal escape. However, the accumulation of LNPs in the liver severely limits the targeting and treatment of mRNA-LNP technology beyond the liver. To overcome this obstacle, researchers have been focusing on various means to achieve precise delivery of extrahepatic tissues and organs. This article mainly expounds the research progress of LNP-specific delivery mRNA from three aspects: endogenous targeting, active targeting and selection of administration route, in order to provide ideas and directions for the design of new mRNA-LNP delivery systems in the future.

Abstract: Objective To evaluate the performance of QuantiFERON-TB Gold Plus (QFT-Plus) in screening the prison population for latent tuberculosis infection (LTBI), and analyze the related influencing factors of latent infection, so as to provide the basis for screening the prison population for latent tuberculosis infection. Methods The basic characteristics and screening results of the newly admitted prison population were collected, using QuantiFERON-TB Gold (QFT-GIT) assay as the gold standard. The kappa value and the area under the ROC curve were used to evaluate the detection performance of QFT-Plus. At the same time, Kruskal-Wallis test was used to compare the difference of IFN-γ production between tubes. A logistic regression model was established to analyze the influencing factors of latent tuberculosis infection in the prison population. Results A total of 100 valid subjects were included in this study, and 24 LTBI patients were screened. The median age of the participants was 38 years, with a median LTBI age of 44 years and a median healthy age of 37 years. In addition, the education level was mainly concentrated in college and above. Consistency checks of various screening methods revealed that the highest coincidence rate of QFT-Plus and QFT-GIT detection results was 0.917, with the largest area under the curve at 0.958. The K-W analysis showed that the amount of IFN-γ in QFT-Plus TB tube was significantly higher than that in QFT-GIT TB tube, and the variation range of IFN-γ in QFT-Plus tube was greater. In addition, multivariate analysis showed that increasing age (aOR: 1.046, 95%CI: 1.004-1.089) was a risk factor for LTBI in the prison population, while having an education level of college or above (aOR: 0.263, 95%CI: 0.071-0.972) was a protective factor. Conclusions QFT-Plus, as a newly developed method for detecting LTBI, showed basic consistency with QFT-GIT, and the consistency was higher than that of other skin test methods. However, due to the large variation of IFN-γ production in QFT-Plus, it is still necessary to further explore the diagnostic threshold. In the screening of LTBI in prisons, special attention should be given to the elderly population and the population with low education levels.

A three-dimensional(3D)medical image segmentation network(CA-SegResNet)which incorporates a 3D coordinate attention mechanism is proposed to address the issue of segmenting identified vertebral bones from spinal computed tomography(CT)images.The network extracts image features through a deep residual convolutional neural network and fuses the feature maps from each encoder layer with the input of the corresponding decoder layer.Subsequently,a 3D coordinate attention module is introduced to capture inter-channel relationships as well as directional and positional information,establishing long-range dependencies across different spatial directions,thereby enabling precise segmentation of the identified vertebral bones.For the segmentation tasks involving the identified cervical vertebra(the 7th cervical vertebra)and the identified thoracic vertebra(the 12th thoracic vertebra)across 105 cases,CA-SegResNet achieves average Dice similarity coefficients(DSC)of 0.934 5 and 0.918 9 on the test set,with average Hausdorff distances(HD)of 7 and 8 mm.Compared with U-Net results,the average DSC is improved by 0.014 5 and 0.0463,while average HD is reduced by 176 and 388 mm.The results demonstrate that the network can realize the precise segmentation of identified vertebral bones from CT images.

Objective　To assess the willingness of students with latent tuberculosis infection (LTBI) in Jiangsu Province to undergo preventive treatment and identify factors influencing their decision, aiming to provide insights for tuberculosis prevention and control strategies in school. Methods The physical examination information of tuberculosis latent infection cases was collected from screenings of new school enrollment and contacts of tuberculosis patients in 6 cities of Jiangsu Province from December 2022 to December 2023. Data on past medical history and understanding of preventive treatment were gathered through an online questionnaire survey on the website of Juanxing, and the influencing factors related to the willingness to take preventive medication were analyzed by logistic regression analysis model. Results In December 2022 to December 2023, a total of 13 school tuberculosis outbreaks occurred in 6 cities, and 1 661 contacts were screened, among which 162 cases met the criteria for prophylactic medication, 96 cases were included in the study by filling in the questionnaire. A total of 22 600 new students from 56 schools participated in the TB screening upon enrollment, of which 358 tested positive for the tuberculin skin test alone, meeting the criteria for preventive medication, and 251 of them completed the willingness survey. Finally, 347 students who met the criteria for preventive treatment were included in the study, with 164 expressing to accept preventive treatment representing a treatment acceptance rate of 47.3%. The results of multivariate analysis showed that university (OR=17.950, 95%CI: 3.078-104.686, P=0.001) and contact with the source of school tuberculosis epidemic (OR=19.542, 95%CI: 6.289-60.726, P<0.001) were associated with increased willingness to receive preventive treatment, while unclear whether to pay for the drugs themselves (OR=0.349, 95%CI:0.133-0.916, P=0.032) was associated with decreased willingness to receive preventive treatment. Compared with Huai'an City, the willingness to receive preventive treatment was significantly lower among students from Nantong City (OR=0.005, 95%CI:0.000-0.063, P<0.001), Nanjing City (OR=0.022, 95%CI: 0.003-0.703, P<0.001) and Lianyungang City (OR=0.074, 95%CI:0.008-0.703, P=0.023). Conclusions The acceptance rate of preventive treatment among LTBI students in Jiangsu Province is not high and is affected by multiple factors. Health education and medication mobilization for preventive medication are essential.

Objective:To explore the direct economic burden and factors affecting out-of-pocket direct costs of multidrug-/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) patients in Jiangsu Province.Methods:MDR/RR-PTB patients diagnosed and treated at 13 municipal tuberculosis (TB)-designated hospitals in Jiangsu Province between January 1, 2021, and December 31, 2022, were included, and basic information and direct economic costs were obtained through questionnaires and hospital information systems. Stepwise multiple linear regression was used to analyze the factors influencing patients' out-of-pocket direct costs.Results:The age of the 233 MDR/RR-PTB patients was (44.04±15.64) years. The M( Q1, Q3) direct medical expense of the patients was 134 051.00 (98 934.01,163 205.73) Yuan, of which the M( Q1, Q3) reimbursement by health insurance or policy reduction was 100 462.10 (78 120.00,130 816.00) Yuan, and the M( Q1, Q3) out-of-pocket direct medical expense was 21 694.62 (14 734.83,37 813.00) Yuan. The M( Q1, Q3) direct non-medical expense was 4 971.00 (3 138.00,7 870.00) Yuan. Age, registered residence location, TB resulting in divorce or separation from spouse or partner, drug resistance test results, and treatment regimens were the influencing factors associated with out-of-pocket direct costs for MDR/RR-PTB patients. Conclusions:The direct economic burden caused by MDR/RR-PTB in Jiangsu Province is heavy. It is necessary to emphasize psychological guidance and care for MDR/RR-PTB patients, improve the diagnosis, treatment, and management of MDR/RR-PTB, and effectively reduce the economic burden of MDR/RR-PTB patients.

Objective　To explore the association between outdoor air pollutants sulfur dioxide (SO2) and nitrogen dioxide (NO2) exposure and latent tuberculosis infection (LTBI) risk among middle school students. Methods　Basic information and LTBI screening results were collected from students undergoing entrance physical examinations in 68 middle schools across six prefecture-level cities in eastern China from 2018 to 2021. The LTBI test was conducted using the purified protein derivative method. Additionally, data on outdoor air pollutant concentrations and meteorological factors in these six cities from 2015 to 2021 were extracted. A generalized additive model was employed to assess the impact of SO2 and NO2 exposure on the risk of LTBI among middle school students, and sensitivity and subgroup analyses were further performed. Results　A total of 198 275 students were included in the final analysis, of which 11 721 students were diagnosed with LTBI. Compared with the non-LTBI group, the LTBI group had a higher proportion of males and Han ethnicity, as well as older age and higher body mass index (all P<0.001). With every 10 units increase in SO2 concentration, LTBI risk increased by 12.22% (95%CI: 4.47-20.54), 23.25% (95%CI:16.13-30.81), and 22.77% (95%CI:16.78-29.07) at lag times of one year, two years, and three years, respectively. Similarly, for every 10 units increase in NO2 concentration, LTBI risk increased by 22.20% (95%CI: 17.23-27.38), 27.22% (95%CI: 21.41-33.31), and 32.05% (95%CI: 25.76-38.65), respectively, at the corresponding lag times. Furthermore, the positive association between SO2 and NO2 concentrations and the risk of LTBI was robust in the sensitivity analyses and remained significant in both male and female students. Conclusions　Outdoor air pollutants SO2 and NO2 exposure are positively associated with the risk of LTBI among middle school students. Since many developing countries face the dual challenges of high LTBI rates and severe outdoor air pollution, reducing outdoor air pollutant concentrations may help mitigate the tuberculosis burden in these countries.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

Objective:To investigate the clinical efficacy of manual reduction under general anesthesia combined with anterior cervical discectomy and fusion (ACDF) in the treatment of lower cervical locked facet dislocation.Methods:Retrospectively analyzed were the data of 53 patients with traumatic single segment dislocation of lower cervical spine combined with single/bilateral facet articular lock who had been admitted to Department of Orthopaedic Spine Surgery, Xiangya Hospital, Central South University from January 2019 to December 2020. There were 36 males and 17 females, aged from 18 to 64 years (average, 45.5 years). All the patients were treated with ACDF under neuroelectrophysiological monitoring. Clinical efficacy was assessed by observing complications and comparing American Spinal Injury Association (ASIA) grading, Modified Japanese Orthopaedic Association (mJOA) scores, neck disability index (NDI) and visual analogue scale (VAS) before and after surgery.Results:All patients were followed up for 16 to 30 months (mean, 24 months). All incisions healed by primary intention with no infection after operation. There were 2 cases of delirium, 9 cases of abdominal distension, 4 cases of lower extremity venous thrombosis, and one case of central diabetes insipidus. Postoperative imaging data showed that all patients achieved sequential reduction of the cervical spine, intervertebral bony fusion, and no internal fixation loosening. The last follow-up showed that the overall improvement rate of ASIA grading of spinal cord function was 84.9% (45/53) compared with the preoperation and that the VAS score (2.0±0.5), mJOA score (13.1±3.1) and NDI index (16.6±5.9) were significantly improved compared with the preoperative values (7.5±1.5, 6.9±3.5, and 37.8±7.8) ( P< 0.05). Conclusion:On the premise of fully assessing the patient's injury status, manual reduction under general anesthesia combined with ACDF is a safe and effective treatment of single-level lower cervical fracture combined with facet dislocation.

Objective:To analyze the risk factors of acute renal injury (AKI) after coronary artery bypass grafting (CABG) in the elderly patients.Methods:A total of 423 patients aged over 60 years who underwent CABG in Linyi People′s Hospital from May 2014 to May 2010 were retrospectively analyzed. Patients were divided into AKI group and control group according to whether AKI occurred. The risk factors of AKI were analyzed by multivariate logistic regression.Results:Among the 423 patients, 62 cases(14.7%)developed postoperative acute kidney injury. Compared with the patients without AKI ( n=361), the proportions of patients with hypertension, heart function (NYHA) ≥ Ⅲ, atrial fibrillation and cardiopulmonary bypass were higher in AKI group, the proportion of patients using statins before operation was lower [71.0%(44/62) vs. 50.7%(183/361),χ 2 =8.75, P<0.01;38.77%(24/62) vs. 7.5%(27/361),χ 2 =48.67, P<0.01;16.1%(10/62) vs. 4.4%(16/361),χ 2 =12.55, P<0.01;51.6%(32/62) vs. 21.3%(77/361),χ 2 =25.37, P<0.01;59.7%(37/62) vs. 85.6%(309/361),χ 2=23.87, P<0.01]. Patients in AKI group had higher level of blood uric acid, urea nitrogen and creatinine [353.8(275.5, 462.5)μmol/L vs. 314.5(262.9, 383.6)μmol/L, Z=2.75, P=0.01;5.5(4.3, 8.2)mmol/L vs. 5.1(4.3, 6.4)mmol/L, Z=2.44, P＝0.02; 74.9(58.5, 92.7)μmol/L vs. 67.0(57.1, 76.3)μmol/L, Z=2.90, P=0.01];and longer operation time, more blood loss and blood vessel bridge than those in control group [(403.2±124.1) vs. (350.6±110.2), t =3.41, P<0.01;(4.0±0.9) vs. (3.7±0.8), t=2.83, P=0.01;(3.8±0.7) vs. (3.5±0.8), t=3.58, P<0.01]. The multivariate logistic regression analysis showed that preoperative cardiac function (NYHA)≥Ⅲ( OR=8.528,95% CI:3.734-19.477, P<0.01),hypertension( OR=6.455,95% CI:2.605-15.997, P<0.01),extracorporeal circulation( OR＝3.046,95% CI:1.190-7.795, P=0.02),diabetes mellitus( OR=2.294,95% CI:1.047-5.026, P=0.04),elevated serum uric acid level( OR=1.004,95% CI:1.000-1.008, P=0.03)were the independent risk factors for AKI. Statins is a protective factor for postoperative AKI( OR=0.366,95% CI:0.154-0.873, P=0.02). Conclusions:AKI is a common complication after CABG in elderly patients. Cardiac function(NYHA) ≥ Ⅲ,hypertension,extracorporeal circulation,diabetes mellitus,elevated serum uric acid level are risk factors and administration of stating is protective factor for the incidence of acute kidney injury in elderly patients after coronary artery bypass grafting.