Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

This study is designed to address the development, synthesis, and screening of non-animal-derived nanoantibody libraries. Furthermore, it seeks to elucidate the impact of framework region selection and complementarity-determining region (CDR) design on the characteristics of synthesized nanoantibody libraries. These investigations aim to establish a robust theoretical and technical foundation for enhancing the efficacy, diversity, and practical applicability of synthetic nanoantibody libraries. In this study, a new framework (IGHV3S65*01-IGHJ4*01) was identified based on the high-throughput sequencing results of natural nanobodies, and degenerate primers were designed based on the frequency of amino acids at each position in the complementarity-determining region (CDR) region to synthesize the coding fragments of nanobodies by overlap PCR. After 40 times of electro-transformation, a single-frame synthesized nanobody library (SS-Library) containing 6×10⁹ clones was obtained, and the titer of the library was demonstrated to be 10¹³ PFU/mL after rescue by the helper phage M13K07. Random 48 single colonies were picked for PCR, which revealed an insertion rate of 95.8%. Sanger sequencing results showed that 38 clones had complete sequences, none of which showed cysteines or stop codons, and no identical sequences appeared, suggesting that the library had higher diversity. The library was screened and validated with three antigens, including bovine serum albumin (BSA), acetylcholinesterase (AchE), and immunoglobulin G (IgG). Finally, 2 nanobodies against BSA, 10 against AchE, and 15 against IgG were obtained. One positive clone of each antigen was singled out for recombinant expression, and the results showed that all the three nanobodies were expressed in a soluble form. The binding activity of recombinantly expressed nanobodies was evaluated using indirect enzyme-linked immunosorbent assay (ELISA) and bio-layer interferometry (BLI). The results demonstrated that the anti-AChE and anti-IgG nanobodies exhibited specific binding to their respective antigens, with affinity constants (KD) of 294 nmol/L and 250 nmol/L, respectively. The nanobody synthetic library preparation method proposed in this study is simple and easy to use with low preference, and it is expected to be a universal nanobody discovery platform for the preparation and development of lead specific nanobodies.
Single-Domain Antibodies/biosynthesis* ; Peptide Library ; Complementarity Determining Regions/immunology* ; Animals

Objective:To explore the rules of Traditional Chinese Medicine (TCM) prescriptions of gastroesophageal reflux disease based on Ancient and Modern Medical Records Cloud Platform.Method:The relevant medical cases from ancient medical case database, modern medical case database, shared medical case database and famous doctors' medical case database in Ancient and Modern Medical Records Cloud Platform (V2.3.8) were selected, and frequency analysis, attribute analysis, association analysis, cluster analysis and complex network analysis were performed on the herbs.Results:A total of 107 medical records were obtained, including 225 TCMs. The core medicines were Radix et Rhizoma Glycyrrhizae, Pericarpium Citri Reticulatae, Rhizoma Coptidis, Poria, and Fructus Evodiae. The drug property was mainly cold and warm, and the herbal tastes bitter and pungent. The meridian tropism of drugs mainly manifested in the spleen and stomach meridians. The core herbal pairs were Radix et Rhizoma Glycyrrhizae and Pericarpium Citri Reticulatae. The core prescription consisted of 17 herbs including Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Rhizoma Coptidis, Fructus Evodiae, Poria, Endoconcha Sepiae, Herba Taraxaci, Fructus Aurantii, Radix Paeoniae Alba, Radix Bupleuri, Jiang Banxia, Rhizoma Cyperi, Radix Aucklandiae, Caulis Bambusae In Taenia, Fructus Aurantii Immaturus, Fructus Amomi, and Rhizoma Atractylodis Macrocephalae. Conclusions:Chinese medicine treatment of gastroesophageal reflux disease is mainly based on Chaihu Shugan Powder, Zuojin Pill, and Wendan Decoction. Moreover, we need to combine with clinical symptoms to add or subtract herbs.

Objective:To explore the currents status of central vascular access devices (CVADs) in children's medical center in China and to provide a reference for the standardized use of CVADs and specialized nursing as well as a basis for pediatric intravenous therapy management.Methods:Totally 31 hospitals of Futang Research Center of Pediatric Development, children's hospitals of the medical treatment alliance as well as women and children care centers and general hospitals with pediatric departments were selected by convenient sampling from July 23rd to 31st, 2018. All the pediatric patients using CVADs were investigated with the Central Vascular Access Device Questionnaire which was designed by the research group, and the incidence of complications was also observed. Totally 1 333 questionnaires were collected, among which 1 288 were valid, accounting for an effective recovery rate of 96.62%.Results:There were 22 ClassⅢ and 9 ClassⅡ hospitals among the 31 hospitals. Among the 1 288 pediatric patients who used CVADs, 860 used peripherally inserted central catheters (PICC) , accounting for 66.77%; 342 used central venous catheters (CVC) , accounting for 26.55%; 77 used implantable venous access port (PORT) , accounting for 5.98%; and 9 used umbilical venous catheters, accounting for 0.70%. CVADs were mainly used in the Departments of Hematological Neoplasms, ICU, Intensive Care Unit Pediatric Surgery, Vasculocardiology and Neonatals. PICC, CVC and PORT were mainly applied to upper extremities (90.00%, 74 cases) , jugular vein (73.39%, 251 cases) and the breast (96.10%, 74 cases) respectively. In the maintenance of CVADs, there was the problem of co-existing dressings.Conclusions:CVADs have been widely used in pediatric patients, and the choice of CVADs is relatively standardized. However, the maintenance of the catheters, the use of dressings, the selection of infusion connectors and the control of related complications still need to be strengthened. It is recommended that nursing professionals and nursing managers should further strengthen their knowledge about the placement and maintenance of CVADs, and intensify their management and supervision in accordance with international and national guidelines and standards for intravenous infusion therapy to further reduce the incidence of vascular access complications in pediatric patients.

This work was supported by Science and Technology Program of Health and Family Planning Commission of Jiangxi Province (No.20161106) Abstract Objective: To investigate the prognostic value of subventricular zone (SVZ) invasion in glioma patients. Methods: The clini-cal data of 175 patients with glioma diagnosed based on pathology in Jiangxi Province Cancer hospital between January 2010 and July 2015 were analyzed retrospectively. There were 59 cases of World Health Organization (WHO) gradeⅡ, 59 cases of WHO gradeⅢ, and 57 cases of WHO gradeⅣat the first diagnosis. There were 75 cases of SVZ invasion (SVZ+) and 100 cases of SVZ non-invasion (SVZ-) according to preoperative magnetic resonance imaging. The survival outcomes of both cohorts were compared using the Log-rank test. The correlation between the recurrence pattern and SVZ involvement was analyzed using Chi-square tests. Results: The me-dian follow-up time was 63 months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 42.2% and 37.5%, respectively. These were 20.9% and 15.3% in the SVZ+group, compared with 57.1% and 44.1% in the SVZ-group, respectively (P<0.001 and P<0.001, respectively). The SVZ+group had fewer cases of total resection, larger lesions (maximum diameter greater than 5.0 cm), and more cases of gradeⅣ(P<0.001, P<0.001, and P=0.018, respectively). There were 89 cases of recurrence. The total recur-rence rate was 62.7% in the SVZ+group, compared with 42.0% in the SVZ-group (P=0.007); the distant recurrence rates were 21.3% and 7.0% (P=0.004), respectively. Conclusions: SVZ invasion is a poor prognostic factor for OS and PFS in gliomas, which is positively correlated with a low total resection rate, large lesions, and gradeⅣlesions, and increases the probability of total recurrence and dis-tant recurrence.

Objective:To assess the prognostic factors of World Health Organization(WHO)grade Ⅱ gliomas.Methods:A total of 146 patients diagnosed with WHO grade Ⅱ gliomas were treated at Jiangxi Province Tumor Hospital between June 1997 and April 2015,in-cluding 90 gross total resections(GTRs)and 56 partial resections.According to the 2007 WHO grading system of gliomas,there were 96 astrocytomas,30 oligodendrogliomas,and 20 oligoastrocytomas.Results:The median follow-up time was 88 months.Five-year overall survival(OS)and progression-free survival(PFS)rates were 75.7% and 60.0%,respectively,and 10-year OS and PFS rates were 57.4% and 37.8%,respectively.Univariate analysis of OS revealed statistically significant differences in age,sex,subventricular zone (SVZ) invasion, peritumoral edema, residual tumor volume, preoperative tumor size and numbers, and the extent of resection (P<0.05). Compared with astrocytoma patients, oligodendroglioma patients had better OS and PFS (P=0.040 and 0.049, respectively). Among those factors,sex,SVZ invasion,residual tumor volume,preoperative tumor numbers,and the extent of resection were like-wise significant for PFS (P<0.05). Multivariate analysis revealed that the extent of resection, SVZ invasion, and peritumoral edema were independent prognostic factors for OS(P<0.05)and the extent of resection and tumor numbers were independent prognostic fac-tors for PFS(P<0.05).Sixty patients developed recurrences,including 53 tumor bed failures and 7 intracranial disseminations.Conclu-sions:The extent of resection,SVZ invasion and peritumoral edema may be independent prognostic factors for OS in low-grade glio-mas.Postoperative radiotherapy would improve PFS for patients who underwent GTRs.The major pattern of failure was tumor bed re-currence.

Objective To explore ultrasonographic characteristics and prognosis of cesarean scar pregnancy in the ultrasound.Methods To conducted a retrospective study of 8 cases of diagnoses of cesarean scar pregnancy in ultrasound in our hospital from January 2013 to August 2015.All cases had ultrasonographic examinations regularly during the pregnancy and were confirmed placenta increta by cesarean section or prenatal MRI (6 cases).The imaging characteristics of 8 cases of pregnant women in early pregnancy by transvaginal ultrasound,and the positions of gestational sac and chorion frondosum were observed.Ultrasonic follow-up results,numbers of cesarean delivery,final diagnosis,and pregnancy outcome were analyzed.Results Eight cases of patients were diagnosed cesarean scar pregnancy,and all of ceses were diagnosed placenta increta by ultrasound from 11 weeks to 24 weeks of gestation.It was found that the positions of chorion frondosum were located in the lower edge of gestational sac in Two-dimensional ultrasound and the chorion frondosum was covered in cesarean section scar.The echoes of proliferous chorion frondosum were stronger than the rest of chorion leve and decidua reflexa,and the thickness of proliferous chorion frondosum were thicker than the rest of chorion leve and decidua reflexa.In the follow-up ultrasound of 8 cases in the second trimester,the original position of chorion frondosum which covered and the position of placenta were roughly similar.The position of placenta did not move up with the gestational weeks,in addition,appeared as placenta previa and covered in cesarean section scar.Five patients had strong childbearing willing of continue to conceive,one case of which needed hysterectomy,four of which underwent cesarean section delivery with alive births after using bilateral iliac arteries balloon occlusion.The rest 3 cases underwent induction of labor after using bilateral iliac arteries balloon cclusion.Conclusions Cesarean scar pregnancy in first pregnancy may be develop as placenta accreta in second and third trimester pregnancy.If chorion frondosum was observed to cover cesarean section scar by ultrasound in early pregnancy,scar pregnancy diagnosis was established.Pregnant women who have strong willing to continue their pregnancy should be pay more attentin to thiers placenta previa and placenta percreta in second and third trimester pregnancy.Close follow-up are needed.

Objective To describe the epidemic of imported infectious diseases in China between 2013 and 2016, including the kinds of infectious diseases, affected provinces, source countries and the epidemiological characteristics, and provide scientific information for the prevention and control of imported infectious diseases. Methods Data of cases of imported infectious diseases in China from 2013 to 2016 were collected from national information reporting system of infectious diseases, Microsoft Excel 2010 and SPSS 18.0 were used to conduct data cleaning and analysis. Results From 2013 to 2016, a total of 16206 imported cases of infectious diseases were reported in China. Of all the cases, 83.12%(13471 cases) were malaria cases, followed by dengue fever (2628 cases,16.22%). The majority of the imported cases were males (14522 cases, 89.61%). Most cases were aged 20-50 years. Except Zika virus disease and yellow fever, which were mainly reported before and after spring festival, other imported infectious diseases mainly occurred in summer and autumn. The epidemic in affected provinces varied with the types of infectious diseases, and Yunnan reported the largest case number of imported infectious diseases, followed by Jiangsu, Guangxi and Guangdong. The imported cases were mainly from Asian countries, such as Burma, and African countries, such as Angola, Equatorial Guinea and Ghana, which also varied with the types of infectious diseases. Conclusions We should pay more attention to imported infectious diseases and strengthen the prevention and control measures in our country. In order to reduce the incidence of imported infectious diseases, the health education should be enforced for persons who plan to travel abroad and the active surveillance should be strengthened for returned travelers.

Objective To investigate the ultrasound characteristics of congenital cystic adenomatoid malformation (CCAM). Methods The ultrasonographic features of 21 cases of fetal CCAM confirmed by prenatal ultrasound were analyzed. And ultrasound ifndings were compared with the postnatal thoracic computed tomography (CT), surgical result and follow-up data. Results (1) Prenatal ultrasonographic ifndings:2 cases of CCAM typeⅠ(10%, 2/21), 13 cases of typeⅡ(62%, 13/21), and 6 cases of typeⅢ(28%, 6/21). Of them, 95%(20/21) lesions were located in unilateral thorax, while 5%(1/21) in bilateral thorax. CCAM was ifrst detected at 18th-25th gestational week with a median of 22nd week. The CVR was<1.6 and>1.6 in 16 (76%, 16/21) and 5 (24%, 5/21) cases respectively. After reaching the maximum volume, the size of mass remained stable in 8 cases and regressed in 13 cases with even complete remission in 5 cases. There were mediastinal shift in 19 fetuses (90%, 19/21), polyhydramnios in 6, and concomitant structural abnormalities in 3 cases such as pulmonary sequestration, diaphragmatic hernia and fetal hydrops. (2) Clinical outcomes:15 newborns were conifrmed as CCAM by CT, in which 9 cases underwent surgical resection. One case was conifrmed by autopsy. Nineteen cases showed good prognosis. Whereas 1 pregnancy with fetal hydrops was terminated, and 1 fetus with diaphragmatic hernia died after birth. Conclusions Dynamic prenatal ultrasound assessment is the key factor in prognosis prediction of fetal CCAM. CCAM without other structural abnormalities has a good outcome.

OBJECTIVETo investigate the epidemiological characteristics of human infections with avian influenza A (H7N9) in China and to provide scientific evidence for the adjustment of preventive strategy and control measures.

METHODSDemographic and epidemiologic information on human cases were collected from both reported data of field epidemiological investigation and the reporting system for infectious diseases.

RESULTSA total of 433 cases including 163 deaths were reported in mainland China before June 4, 2014. Two obvious epidemic peaks were noticed, in March to April, 2013 and January to February, 2014. Confirmed cases emerged in 14 areas of China. Five provinces, including Zhejiang, Guangdong, Jiangsu, Shanghai, and Hunan, reported about 85% of the total cases. Median age of the confirmed cases was 58 years (range, 1-91), with 70% as males. Of the 418 cases with available data, 87% had ever exposed to live poultry or contaminated environments. 14 clusters were identified but human to human transmission could not be ruled out in 9 clusters.

CONCLUSIONHuman infections with avian influenza A (H7N9) virus showed the characteristics of obvious seasonal distribution, with certain regional clusters. The majority of confirmed cases were among the elderly, with more males seen than the females. Data showed that main source of infection was live poultry and the live poultry market had played a significant role in the transmission of the virus.

Adaptation, Psychological ; Aged ; Animals ; China ; epidemiology ; Demography ; Environmental Pollution ; Female ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; epidemiology ; prevention & control ; transmission ; Male ; Meat ; Poultry ; Research Design