Dengue fever, caused by of dengue virus (DENV) infection, is one of the most prevalent arboviral infections worldwide. It is estimated that approximately 390 million people are infected with DENV each year, of whom approximately 96 million will develop clinical symptoms and one in every twenty people may develop severe dengue leading to shock, internal bleeding and death. DENV includes four serotypes (1-4), each of which can cause various forms of disease. There is currently no specific treatment for dengue fever, and only two vaccines have been approved for use in some countries: CYD-TDV and TAK-003. CYD-TDV, which is suitable for people aged 9-45, can be affected by antibody-dependent enhancement (ADE), leading to more severe infections. Therefore, how to reduce or eliminate ADE becomes an important issue in current dengue vaccine research. In addition, the effects of DENV non-structural proteins on the immune system cannot be ignored. Currently, at least seven dengue vaccines are in various stages of development and clinical trials. This review will focus on three vaccine candidates that have made significant progress, and summarize the ways to avoid ADE the progress in the development of dengue vaccines using non-structural proteins as immunogens.

Objective To investigate the distribution characteristics of serum sIgE antibodies against four allergenic protein components of egg white in children with egg allergy,and then clarify the clinical application value of single component-resolved diagnostics of egg allergy.Methods Serum samples from 197 children with egg allergy were collected.The levels of serum sIgE antibodies against four major allergenic protein components of egg white,including ovomucin,ovalbumin,ovotransferrin,and lysozyme,were detected by the light-excited chemiluminescence assay(LiCA),and the distribution characteristics of sIgE antibodies were analyzed.Results The positive rates of serum sIgE antibodies against ovalbumin,ovomucin,ovotransferrin,and lysozyme in 197 chlidren with egg allergy were 77.16%(152/197),70.56%(139/197),35.02%(69/197),and 18.27%(36/197),respectively.The positive rate of serum sIgE antibody against both ovomucin and ovalbumin was 30.45%.There was a weak correlation between the levels of sIgE antibodies against egg and the cumulative levels of sIgE antibodies against four allergenic protein components(r=0.266 8,P＜0.05).There were signifi-cant individual differences in the levels of serum sIgE antibodies against four allergenic protein components of egg white in the children with egg allergy.Conclusion There is individual heterogeneity in the levels of serum sIgE antibodies against four components of egg white in the children with egg allergy.The detection of sIgE antibodies against egg white components can distinguish different forms of egg allergies,which is of great value for the accurate diagnosis and precise desensitization of children's egg allergy.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Purpose: Titanium implants are widely used in the treatment of dentition defects; however, due to problems such as osseointegration failure, peri-implant bone resorption, and periimplant inflammation, their application is subject to certain restrictions. The surface modification of titanium implants can improve the implant success rate and meet the needs of clinical applications. The goal of this study was to evaluate the effect of the use of porous titanium with a chitosan/hydroxyapatite coating on osseointegration. Methods: Titanium implants with a dense core and a porous outer structure were prepared using a computer-aided design model and selective laser sintering technology, with a fabricated chitosan/hydroxyapatite composite coating on their surfaces. in vivo and in vitro experiments were used to assess osteogenesis. Results: The quasi-elastic gradient and compressive strength of porous titanium implants were observed to decrease as the porosity increased. The in vitro experiments demonstrated that, the porous titanium implants had no biological toxicity; additionally, the porous structure was shown to be superior to dense titanium with regard to facilitating the adhesion and proliferation of osteoblast-like MC3T3-E1 cells. The in vivo experimental results also showed that the porous structure was beneficial, as bone tissue could grow into the pores, thereby exhibiting good osseointegration. Conclusions Porous titanium with a chitosan/hydroxyapatite coating promoted MC3T3-E1 cell proliferation and differentiation, and also improved osseointegration in vitro. This study has meaningful implications for research into ways of improving the surface structures of implants and promoting implant osseointegration.

Objective:To explore the feasibility and safety of minimally invasive surfactant administration (MISA) in preterm neonates with respiratory distress syndrome (NRDS).Methods:In this multicenter prospective randomized controlled trial, 92 preterm infants with gestation age ≤30 weeks and diagnosed with NRDS were enrolled in 8 level Ⅲ neonatal intensive care units (NICU) in Beijing-Tianjin-Hebei Region from 1 st July 2017 to 31 st December 2018. They were randomly assigned to minimally invasive surfactant administration (MISA) group or endotracheal intubation surfactant administration (EISA) group according to random number generated by computer. Infants in both groups received calf pulmonary surfactant preparation at a dose of 70-100 mg/kg. The data of demography, perinatal situation, medication administration, complications, clinical outcomes in the two groups were compared with Chi-square test, Student′s t-test, Mann-Whitney U test or Fisher′s exact test. Results:Among the 92 preterm infants, 53 were males, 39 were females; 47 were in the MISA group (25 males), and 45 were in the EISA group (28 males). The gestational age and birth weight were (29.5±1.2) weeks and (1 271±242) g in all patients, (29.5±1.4) weeks and (1 285±256) g in the MISA group, and (29.6±0.9) weeks and (1 255±227) g in the EISA group. The duration of surfactant infusion and the length of whole procedure in the MISA group were significantly longer than that in the EISA group (60 (18, 270) s vs. 50 (30, 60) s, Z=3.009, P=0.003; 90 (60, 300) s vs. 60 (44, 270) s, Z=3.365, P=0.001). For the outcomes, the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and bronchopulmonary dysplasia (BPD) were lower in the MISA group than in the EISA group (36% (17/47) vs. 67% (30/45), χ 2=8.556, P=0.003; 26% (12/47) vs. 47% (21/45), χ 2=4.464, P=0.035). Conclusions:Minimally invasive surfactant administration is applicable in preterm infants ≤30 weeks gestational age with NRDS. Although the length of whole procedure is longer than route endotracheal administration, the benefit of decreasing the incidences of hsPDA and BPD outweighs this demerit.

Objective: To analyze the stress distribution of different types of bone tissue around porous titanium implant in different mechanical loads and to further evaluate the biomechanical properties of porous titanium implant. Methods: Finite element (FE) models of implant restorations for the maxillary first premolar was established, and the diameter of implants in the models was 4.1 mm. Five models was constructed according to diameter of implant central pillar and the thickness of outer porosity: solid group (group A), central pillar 1.5 and 3.1 mm and outer porosity 30% (group B and C), central pillar 1.5 and 3.1 mm and outer porosity 40% (group D and E). Different loads (150 N vertical force, 50 N lateral force) were applied to the occlusal surface of implant restorations in type Ⅲ bone and maximal von Mises stress was evaluated. Meanwhile, a couple of simplified maxillary part models varied in four types of bone were constructed with the implants bearing load of simulation ultimate force to evaluate the stress distribution of different types of bone. Results: With different mechanical loading, the stress value of bone tissue around porous implant (group B-E) was greater than that in the solid structure (group A). Under the load of simulation ultimate force, the maximum stress of the bone rised with the increase of porosity and thickness of the porous implant. And the maximum stress value of the surrounding bone tissue changed with the change of bone. Under vertical loading, the maximal von Mises stress of the bone around solid implants of group A was 17.56 MPa, which was a little lower than that of group B and C. And the maximal equivalent von Mises stress of group D and E was 69.24 MPa. The results of lateral force and simulation ultimate force loading were similar. The stress of the bone tissue around implant increased with the decrease of bone quality. The maximum stress value of group D implant was 134.95 MPa. Conclusions Porous structure of the implant is conducive to transmit stress to surrounding bone tissue and increases the mechanical stimulation of bone. However, if the value and direction of load are inappropriate or quality of bone is poor, pathological stress may be produced.

Objective: To compare the biomechanical characteristics of four-implants mandibular overdentures supported by Locator attachment or bar-clip attachment under different mechanical loads using three-dimensional finite element analysis method. Methods: Two different models of four-implants supported mandibular overdentures using Locator attachment and bar-clip attachment (hereinafter called Locator model and bar-clip model) were established. Each model was subjected to five different mechanical loading conditions: 100 N vertical loading in central incisor (vertical load of incisor), 100 N vertical loading or oblique loading in canine (vertical or oblique loads of canines), 100 N vertical or oblique loading in mandibular first molar (vertical or oblique loads of mandibular first molar). The stress distributions in implants, peri-implant bone and mucosa were recorded under the above five conditions to evaluate the effects of different attachments on the biomechanical properties of implant-supported mandibular overdentures. Results: Regardless of loading conditions and types of attachments, the stress concentration in implants were located at the neck of implants, and the stress concentration in peri-implant bone was located in the cortical bone. The stress values in mucosa were always much smaller than those in implants and cortical bone. Regardless of loading positions (on canine or on mandibular first molar), the maximum stress at the bone interface around the implant under lateral loading was much higher than that under vertical loading. Under various loading conditions, the stress in implants and cortical bone of the Locator model (the highest von Mise stress value was respectively 79.5 and 22.3 MPa) were lower than that of bar-clip model (the highest von Mise stress value was 110.3 and 28.7 MPa respectively) while the maximum compressive stress in mucosa (0.198 MPa) in Locator model was slightly higher than that in the bar-clip model (0.137 MPa). Conclusions In clinical practice, the lateral force applied to the implant-retained overdenture should be minimized to avoid complications caused by pathological loads. Under the same loading condition, the stress distributions in overdenture using Locator attachment are more dispersed, which is more conducive to long-term stability of implants.

OBJECTIVETo compare the effect of different surface processes on bond strength and microscopic structure using a scanning electron microscope (SEM) and an energy distribution spectrum (EDS) at the bonding interface between zirconia framework and veneering ceramic.

METHODSWIELAND zirconia core material was cut into 33 rectangular specimens and fired on into rectangular specimens (10 mm×5 mm×5 mm). The specimens were randomly divided into three groups (n=
11). The sandblasting group was sandblasted before firing. The sandblasting and liner coverage group was sandblasted before firing and then sintered with liner coverage after firing. The control group was not processed. All the veneering ceramics (5 mm×
5 mm×5 mm) were fired on into the zirconia substructure by slip-casting technique. One bilayered specimen in each group was prepared for SEM and EDS to examine the bonding conditions. The other specimens were measured for shear force using an electronic universal dynamometer. The data obtained were analyzed by using the statistical software SPSS 17.0.

RESULTSThe values of the shear bond strength test were (13.80±1.54) MPa for the control group, (18.06±0.59) MPa for the sandblasting group, and (21.04±1.23) MPa for the sandblasting and liner coverage group. Significant differences existed among the three groups (P<0.01).

CONCLUSIONSAbrasion before firing significantly increases the shear bond strength of zirconia to veneering porcelain. The use of porcelain combined with liner increases the shear bond strength.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.