Objective:To study the immunotherapeutic effect of chimeric hepatitis B core protein virus-like particles in subcutaneous lung adenocarcinoma mouse model, lays the foundation for the progression of tumor nano-therapeutic technology development.Methods:The plasmid was constructed by inserting a B-cell epitope of the human epidermal growth factor receptor-2 (HER-2) at hepatitis B core protein′s major immunodominant region (MIR). The recombinant virus nanoparticle, denoted as HBc-HER2, was obtained by E. coli expression system, followed by a series of purification steps. The immune response to this recombinant protein nanoparticle was assessed by measuring levels of anti-HER-2 antibody levels and characterizing antibody isotypes in a subcutaneous tumor mice model of lung adenocarcinoma. While tumor therapeutic efficacy was evaluated by measuring tumor size changes with an electronic caliper and MRI photography of subcutaneous tumor in mice.Results:A high-purity HBc-HER2 recombinant protein was obtained and could assemble into nanoparticle. Animal studies had demonstrated the robust immunogenicity of this vaccine in inducing high levels of HER-2 specific antibodies, yielding positive therapeutic outcomes against tumors.Conclusions:The engineered HBc-HER2 demonstrated notable tumor therapy efficacy in a subcutaneous lung adenocarcinoma mouse model, offering a foundation for tumor therapeutic nanotechnology vaccine research.

OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.

Objective:To identify the influencing factors for community elderly health services provided by general practitioners (GPs) using the social ecological theory, for reference in improving their participation and satisfaction.Methods:According to the social ecological theory, an ecological model for GPs to carry out community elderly health services was constructed from four levels: public policy ecology, community health service ecology, interpersonal relationship ecology, and individual characteristics ecology of general practitioners. A survey questionnaire was designed with six latent variables: public health policy support, public health service and basic medical service supply, doctor-patient relationship, individual participation and individual satisfaction. The questionnaire was distributed to 220 GPs from 11 primary healthcare institutions in Jiangsu province, China, who were randomly selected between October and November 2021. Exploratory and confirmatory analyses of the model were conducted using AMOS 25.0.Results:A total of 207 valid questionnaires were collected, and all the KMO values of the six latent variables were greater than 0.7, while the composite reliability values and average variance extracted values greater than 0.7 and 0.5, respectively. Both the reliability and validity of the data met the analysis requirements. Exploratory analysis revealed that public health policy support had a direct positive effect on both public health service and basic medical service supply (both effect sizes being 0.37). Public health service had a direct positive effect on doctor-patient relationship, individual participation and individual satisfaction (effect sizes being 0.52, 0.22, and 0.31, respectively). The direct effect of basic medical service supply on doctor-patient relationship was not significant (effect size being 0.03), but it had a direct positive effect on public health service (effect size being 0.46). Doctor-patient relationship had a direct positive effect on individual participation (effect size being 0.51), but its direct effect on individual satisfaction was not significant (effect size being 0.06). Individual participation had a direct positive effect on individual satisfaction (effect size being 0.52). Conclusions:By optimizing the public policy ecosystem, community health service ecosystem, and interpersonal relationship ecosystem, the participation and satisfaction of general practitioners can be systematically improved.

Calcium ; Homeostasis ; Humans ; Parkinson Disease/therapy*

Background and Objectives: RUNX2 plays an essential role during the odontoblast differentiation of dental pulp stem cells (DPSCs). RUNX2 Exon 5 is an alternative exon and essential for RUNX2 transcriptional activity. This study aimed to investigate the regulatory mechanisms of RUNX2 exon 5 alternative splicing in human DPSCs. Methods: and Results: The regulatory motifs of RUNX2 exon 5 were analyzed using the online SpliceAid program. The alternative splicing of RUNX2 exon 5 in DPSCs during mineralization-induced differentiation was analyzed by RT-PCR. To explore the effect of splicing factor YBX1 on exon 5 alternative splicing, gaining or losing function of YBX1 was performed by transfection of YBX1 overexpression plasmid or anti-YBX1 siRNA in DPSCs. Human RUNX2 exon 5 is evolutionarily conserved and alternatively spliced in DPSCs. There are three potential YBX1 binding motifs in RUNX2 exon 5. The inclusion of RUNX2 exon 5 and YBX1 expression level increased significantly during mineralization-induced differentiation in DPSCs. Overexpression of YBX1 significantly increased the inclusion of RUNX2 exon 5 in DPSCs. In contrast, silence of YBX1 significantly reduced the inclusion of exon 5 and the corresponding RUNX2 protein expression level. Knockdown of YBX1 reduced the expression of alkaline phosphatase (ALP) and osteocalcin (OC) and the mineralization ability of DPSCs, while overexpression of YBX1 increased the expression of ALP and OC and the mineralization ability of DPSCs. Conclusions Human RUNX2 exon 5 is conserved evolutionarily and alternatively spliced in DPSCs. Splicing factor YBX1 promotes the inclusion of RUNX2 exon 5 and improves the mineralization ability of DPSCs.

Objective:To analyze the hospitalization expenses of elderly patients with hypertension and its influencing factors, so as to provide reference for optimizing the medical service management of elderly patients with hypertension.Methods:Medical record home page data of all hypertension inpatients of elderly patients at two tertiary general hospitals in Jiangsu province from 2017 to 2020 were retrieved. These data were used to analyze the basic information, hospitalization expenses and their influencing factors. Descriptive analysis was used for all data, variance analysis was used for one-way analysis, and multiple linear regression was used for multivariate analysis.Results:A total of 20 596 elderly inpatients with hypertension were included in this study. The number of patients was increased from 1 476 in 2017 to 10 771 in 2020. Among them, the number of inpatients with≥2 diseases increased from 1 105(74.86%) to 10 564(98.08%); From 2017 to 2020, the average hospitalization expenses of elderly inpatients with hypertension were 11 500 yuan, 13 600 yuan, 13 800 yuan and 14 100 yuan respectively, increasing year by year; Gender, age, number of hospitalizations, hospitalization days and number of diseases were the influencing factors of hospitalization expenses( P<0.05), and the hospitalization expenses increased with the increase of hospitalization days, number of diseases and age. Conclusions:The number of elderly patients with hypertension, the incidence of comorbidity, and the average hospitalization cost in tertiary hospitals in Jiangsu province were increasing year by year. There were many factors affecting the hospitalization cost. The author suggested that the treatment of elderly patients with hypertension should be shifted to prevention, so as to reduce the economic burden of disease and improve their quality of life.

To investigate the clinical and imaging features，diagnosis，treatment and prognosis of patients with wilson disease（WD）.Methods The clinical data of wilson's disease with mental and behavior disorder were analyzed.Results The patient started the disease at the age of 16.At the beginning of the disease，she was talking to herself，laughing and in a daze，which did not attract the attention of her family.The first diagnosis and treatment was not made until the age of 22.Brain atrophy and T-2 high signal in bilateral thalamus，brainstem，cerebellum，pontine arm and putamen were shown on head MRI.K-F ring was positive under slit lamp，ceruloplasmin <3 mg/dl.Gene detection showed ATP7B gene variation.Conclusion When patients start with mental,emotional，and cognitive disorders,accompanied by intracranial symmetrical lesions and combined with systemic multiple system damage，WD should be considered.K-F loop，ceruloplasmin and gene detection are helpful for early diagnosis and treatment.

Objective:To analyze the sensitivity and specificity of SARS-CoV-2 nucleic acid testing in 20 348 close contacts of COVID-19 cases in different prevention and control stages in Guangzhou and to provide scientific evidence for optimizing epidemic response strategies.Methods:A total of 20 348 close contacts of COVID-19 cases in Guangzhou were traced between February 21 and September 22,2020. All the close contacts were tested for the nucleic acid of SARS-CoV-2. The sensitivity and specificity of nucleic acid testing and diagnosis in the different prevention and control stages were compared.Results:In 20 348 close contacts, 12 462 were males (61.24%), the median ( P 25, P 75) of age of them was 31.0 years (23.0,43.0), the median number ( P 25, P 75) of nucleic acid testing for them was 2.0 (1.0,3.0), and the median ( P 25, P 75) of their quarantine days was 12.0 (8.0,13.0) days, respectively. A total of 256 COVID-19 cases were confirmed in the close contacts after seven nucleic acid tests. In the 1 st, 2 nd, 3 rd and 7 th nucleic acid testing, the sensitivity and specificity were 69.14% and 99.99% (177 cases confirmed), 89.84% and 99.99% (230 cases confirmed), 97.27% and 99.99% (249 cases confirmed), and 100.00% and 99.98%, respectively. In the three stages of COVID-19 prevention and control in China: domestic case stage, imported case stage, and imported case associated local epidemic stage, the sensitivity of the 1 st nucleic acid testing was 70.68%, 68.00% and 67.35%, and the specificity was 99.98%, 100.00% and 100.00%, respectively. Conclusions:The sensitivity of nucleic acid testing in the close contacts at the different stages were consistent with slight decrease, which might be related to the increased proportion of asymptomatic infections in the late stage of epidemic prevention and control with COVID-19 in Guangzhou. It is suggested to give three nucleic acid tests to improve the sensitivity and reduce false negative risk.

Objective:To explore the expression of programmed death ligand-1 (PD-L1) protein in grade Ⅲ non-special type invasive breast cancer and its related factors, so as to provide a basis for immunotherapy.Methods:A total of 63 surgically resected specimens of grade Ⅲ non-special type invasive breast cancer diagnosed by pathology in Cancer Hospital & Shenzhen Hospital of Chinese Academy of Medical Sciences from February 2017 to February 2021 were collected. The HE-stained sections were reviewed, and the proportion of immune cells (IC) in all invasive active tumor cells in the tumor sections was calculated. The expression of PD-L1 (SP142) protein in all specimens was detected by immunohistochemistry. The relationship between the positive expression of PD-L1 protein and the clinicopathological parameters was analyzed, and the Pearson correlation test was used to analyze the relationship between the expression of PD-L1 (SP142) and the degree of IC infiltration.Results:Among 63 patients, 19 patients (30.2%) were triple-negative type, 34 patients (53.9%) were luminal type, and 10 patients (15.9%) were human epidermal growth factor receptor 2 (HER2) overexpression type. The positive rate of PD-L1 (SP142) in grade Ⅲ non-special type invasive breast cancer was 77.8% (49/63). The positive rate of PD-L1 (SP142) in triple-negative type was 94.7% (18/19), the positive rate in non-triple-negative type was 70.5% (31/44), and the difference between the two groups was statistically significant ( P = 0.047). The positive rate of PD-L1 (SP142) in estrogen receptor (ER)-negative patients or progesterone receptor (PR)-negative patients was both 90.3% (28/31), which was higher than that of ER-positive patients or PR-positive patients (65.6%, 21/32), and the difference was statistically significant ( P = 0.018); the positive rate of PD-L1 (SP142) was not related to the patient's age, tumor site, tumor maximum diameter and number, vascular tumor thrombus, nerve invasion, lymph node metastasis, HER2 status and Ki-67 positive index (all P > 0.05). The expression of PD-L1 was positively correlated with the degree of IC infiltration ( r = 0.716, P<0.001). Conclusion:In grade Ⅲ non-special type invasive breast cancer, the patients with triple-negative type has a high positive rate of PD-L1, and the patient with negative ER or PR has a high positive rate of PD-L1; the tumor IC infiltration is positively correlated with the expression of PD-L1.

ObjectiveTo investigate whether Xiayuxue decoction exerts an anti-liver fibrosis effect by inhibiting glial cell line-derived neurotrophic factor (GDNF). MethodsA total of 24 C57BL/6 mice were randomly divided into control group, model group, and Xiayuxue decoction group. The mice in the model group and the Xiayuxue decoction group were given intraperitoneal injection of 10% CCl4, and those in the Xiayuxue decoction group were given 0.4678 g/kg Xiayuxue decoction by gavage since week 4. The liver function parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and liver histopathology was observed. Immunohistochemistry was used to measure the protein expression of alpha-smooth muscle actin (α-SMA) and GDNF. GFP-Col-HSC and human primary hepatic stellate cells (HSCs) were treated with GDNF (10 ng/ml), and HSC activation was measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the model group had significant increases in the levels of ALT and AST, and compared with the model group, the Xiayuxue decoction group had significant reductions in the levels of ALT and AST (all P＜0.01). Liver histopathology showed that the model group had marked inflammatory cell infiltration and formation of fibrous septa by proliferated collagen fibers, and the Xiayuxue decoction group had loose fibrous septa and alleviated inflammatory cell infiltration. Immunohistochemistry showed that compared with the control group, the model group had significant increases in the expression of α-SMA and GDNF (both P＜0.01), which were observed in fibrous septa, and compared with the model group, the Xiayuxue decoction group had significant reductions in the expression of α-SMA and GDNF (both P＜0.05). Western blotting showed that the control group had relatively low expression of GDNF in liver tissue, the formation of liver fibrosis at week 6 of CCl4 modeling, and an around 10-fold increase in the expression of GDNF, and the Xiayuxue decoction group had significantly inhibited protein expression of GDNF (P＜0.01); there were significant increases in the expression of α-SMA and collagen type I α1 (Col1) in mice with liver fibrosis, with significant reductions in α-SMA and Col1 after treatment with Xiayuxue decoction (all P＜0.01). The in vitro experiment showed that GDNF induced the significant increases in the protein expression of α-SMA and Col1 in HSCs, which was significantly inhibited by Xiayuxue decoction (all P＜0.01). ConclusionThe expression of GDNF is significantly upregulated in the formation of liver fibrosis. GDNF can induce HSC activation, and Xiayuxue decoction can exert an anti-liver fibrosis effect by inhibiting GDNF.