As an inevitable trend of social development, aging has generated a wide and far-reaching impact on every aspect of society, especially posing severe challenges for the heath system of all countries and regions around the world. Facing the objective reality of humans co-existing with diseases in a long term and people’s ever-growing demand for healthcare, the successful development of vaccine products can provide people with effective preventive measures to combat infectious diseases. This article summarizes the development and use of 4 vaccines that are suitable for the elder population, i.e., influenza vaccine, pneumococcal vaccine, varicella-zoster virus vaccine and respiratory syncytial virus vaccine, aiming to provide some reference for the development and popularization of these vaccines and to improve the well-being of the senior citizens.

BACKGROUND:The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment.On the other hand,although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization,the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE:To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS:SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions(Fe2+)and divalent cobalt ions(Co2+)(Fe-Co/ZIF-8@SLC-0111)was synthesized by ion-exchange reaction and self-assembly,and loaded with hyaluronic acid(HA)by electrostatic adsorption,followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA(abbreviated as FC-S).Meanwhile,nanoparticles Fe-Co/ZIF-8-HA(abbreviated as FC)without SLC-0111 were synthesized by the same method.The nanocomposite platform was tested for particle size,zeta potential,surface morphology,in vitro reactive oxygen species generation,and ability to consume glutathione.Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects.The cytotoxicity of FC-S was detected by CCK-8 assay.Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S.In addition to H2O2,the effects of FC-S and FC on intracellular pH,carbonic anhydrase 9 protein expression,cell viability and apoptosis,intracellular reactive oxygen species and glutathione content,and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION:(1)The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure,uniform size and good dispersion.Its particle size was about 323 nm;zeta potential was about-11.1 mV,and the nanoplatform had a certain reactive oxygen species generation capacity in vitro.(2)FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes.When the mass concentration of FC-S was≤20 μg/mL,there was no obvious cytotoxicity to MG-63 cells and L929 cells,and 20 μg/mL FC-S was selected to act on MG-63 cells in subsequent experiments.(3)Compared with FC group,the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased(P<0.01);the intracellular acidic environment was enhanced;the content of reactive oxygen species was increased(P<0.001);the mitochondrial damage was aggravated;the number of dead cells was increased,and the apoptosis rate was increased(P<0.001).(4)The results indicate that FC-S,as a novel composite nanoplatform,can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production,thus enhancing the efficacy of chemodynamic therapy.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

ObjectiveTo evaluate the effect of multiple punctures on the quality of inactivated poliomyelitis vaccine made from Sabin strains(sIPV)in 5-dose vials.MethodsPre-puncture samples were sampled by opening the cover from 3batches of sIPV stored for about 24 months and balanced at room temperature at least 20 min;The same three batches of sIPV were punctured for the first to fifth needle on the 0,7,14,21 and 28 d respectively,which were balanced at room temperature at least 20 min before each sampling. After sampling,the remaining samples were returned to 2～8 ℃ for preservation. According to the requirements of enterprise registration standard(YBS01052021),all the samples before and after the fifth needle puncture were tested,and the other 4 needle puncture samples were tested for pH,osmotic molar concentration,aseptic test,bacterial endotoxin,D antigen content of typeⅠ,Ⅱ and Ⅲ virus,appearance,abnormal toxicity,protein content and 2-phenoxyethanol content. The relative change rates of 2-phenoxyethanol content,protein content,osmotic molar concentration and D antigen content of typeⅠ,Ⅱ and Ⅲ virus were calculated. SPSS 20 software was used to analyze the relative change rate of each index by one-way ANOVA,and the effect of multiple punctures on the quality of sIPV was evaluated.ResultsThe result of each test item was in compliance with enterprise registration standard before and after each puncture. There was no significant difference between each puncture on the relative rate of change of 2-phenoxyethanol content,protein content,D-antigen content of typeⅡ and Ⅲ virus(F = 2. 125,1. 155,1. 137 and 1. 882,P = 0. 152,0. 386,0. 393and 0. 190,respectively);There was a significant difference in the relative change rate of osmotic molar concentration and Dantigen content of TypeⅠvirus(F = 4. 750 and 4. 010,P = 0. 021 and 0. 034,respectively). The result of Duncan test showed that compared with the first puncture,the relative change rate of osmotic molar concentration after the second and third puncture showed no significant difference,while that after the fourth puncture showed significant difference and a relatively stable result was observed after the fifth puncture. Regarding the relative rate of change of D-antigen content of TypeⅠvirus,there was no significant difference among the first,second,fourth and fifth punctures,while a significant difference existed between the third and the other four punctures.ConclusionFive punctures within 28 days had no effect on the quality of sIPV in 5-dose vials.

Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.
Acute Disease ; Adult ; Basiliximab/therapeutic use* ; Child ; Female ; Graft vs Host Disease/drug therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Steroids/therapeutic use*

Objective:To investigate the risk factors of cardiovascular and cerebrovascular events in patients undergoing maintenance hemodialysis (MHD).Methods:A total of 285 patients undergoing MHD in the Blood Purification Center of Yixing People′s Hospital from May 2013 to March 2018 were enrolled, including 137 patients with cardiovascular and cerebrovascular events and 148 patients without cardiovascular and cerebrovascular events. The demographic and clinical data of patients were retrospectively reviewed. The age, systolic blood pressure, duration of dialysis and prevalence of atherosclerosis were compared between the two groups; the risk factors of cardiovascular and cerebrovascular events were analyzed by multivariate logistic regression.Results:There were significant differences in age, systolic blood pressure, duration of dialysis and prevalence of atherosclerosis; serum creatinine, serum phosphorus, hs-CRP and triglyceride levels between the two groups ( P<0.05). Multivariate logistics analysis showed that age ≥50 years ( B=0.42, 95 %CI 1.06-3.06, P=0.03), duration of dialysis≥24 months ( B=0.85, 95 %CI: 1.23-3.79, P=0.01), atherosclerosis ( B=0.58, 95 %CI: 1.13-4.02, P=0.04), hypertension ( B=0.23, 95 %CI: 1.34-9.25, P<0.01), diabetic kidney disease (DKD) ( B=0.36, 95 %CI:1.19-8.27, P<0.01) , increased hs-CRP ( B=0.83, 95 %CI: 1.12-3.90, P<0.01), high serum phosphorus ( B=0.91, 95 %CI: 1.06-1.54, P<0.01) and elevated TG ( B=0.50, 95 %CI: 1.08-5.57, P<0.01) were independent risk factors for cardiovascular and cerebrovascular events in MHD patients. Early and active intervention of these risk factors may improve the clinical prognosis of MHD patients. The Cox survival curve showed that the probability of cardiovascular and cerebrovascular events increased when the duration of dialysis was>12 months, and it increased more significantly when the duratio n>24 months. Conclusion:The older age, dialysis duration, comorbidities of atherosclerosis, hypertension, DKD, and elevated serum hs-CRP, phosphorus, triglyceride may increase the probability of cardiovascular and cerebrovascular events for MHD patients.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards