Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

Constructing a multi-tiered healthcare security system can meet the diverse and individualized healthcare service demand of the general public.Public hospitals,as the main providers of healthcare services in China,effectively integrate with commercial health insurance,which can accelerate the implementation of high-quality healthcare services,promote innovative development,and optimize product coverage and operational efficiency for commercial health insurance,achieving a win-win situation.Taking Shanghai as the research object,it analyzes the supply and demand status of multi-tiered healthcare security in Shanghai based on population characteristics,economic level,healthcare resources,and policy environment.It identifies the difficulties in the current collaboration between public hospitals and commercial insurance.Finally,it proposes exploring the expansion of independent development space for specialized services,improving the level of coordination between commercial insurance institutions and public hospitals in health management services,promoting the management and sharing of data,strengthening the protection of innovative medicines and devices by commercial insurance,in order to promote the coordinated development of commercial insurance and public hospitals.

Constructing a multi-tiered healthcare security system can meet the diverse and individualized healthcare service demand of the general public.Public hospitals,as the main providers of healthcare services in China,effectively integrate with commercial health insurance,which can accelerate the implementation of high-quality healthcare services,promote innovative development,and optimize product coverage and operational efficiency for commercial health insurance,achieving a win-win situation.Taking Shanghai as the research object,it analyzes the supply and demand status of multi-tiered healthcare security in Shanghai based on population characteristics,economic level,healthcare resources,and policy environment.It identifies the difficulties in the current collaboration between public hospitals and commercial insurance.Finally,it proposes exploring the expansion of independent development space for specialized services,improving the level of coordination between commercial insurance institutions and public hospitals in health management services,promoting the management and sharing of data,strengthening the protection of innovative medicines and devices by commercial insurance,in order to promote the coordinated development of commercial insurance and public hospitals.

Constructing a multi-tiered healthcare security system can meet the diverse and individualized healthcare service demand of the general public.Public hospitals,as the main providers of healthcare services in China,effectively integrate with commercial health insurance,which can accelerate the implementation of high-quality healthcare services,promote innovative development,and optimize product coverage and operational efficiency for commercial health insurance,achieving a win-win situation.Taking Shanghai as the research object,it analyzes the supply and demand status of multi-tiered healthcare security in Shanghai based on population characteristics,economic level,healthcare resources,and policy environment.It identifies the difficulties in the current collaboration between public hospitals and commercial insurance.Finally,it proposes exploring the expansion of independent development space for specialized services,improving the level of coordination between commercial insurance institutions and public hospitals in health management services,promoting the management and sharing of data,strengthening the protection of innovative medicines and devices by commercial insurance,in order to promote the coordinated development of commercial insurance and public hospitals.

Objective To investigate the expression level of plasma miR-34a in patients with diabetic kidney disease(DKD)and its clinical significance.Methods 189 type 2 diabetes mellitus(T2DM)patients treated in our hospital from June 2019 to June 2020 were selected and divided into normal proteinuria group(Nor,UACR<30 mg/g,n=88),microalbuminuria group(Mic,30≤UACR<300 mg/g,n=60)and macroproteinuria group(Mac,UACR≥300 mg/g,n=41)based on the levels of UACR.,During the same period,healthy individuals who underwent physical examination were selected as the normal control group(NC,n=90).Neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM-1)were measured by ELISA.The expression of miR-34a in plasma was measured by reverse transcription-poly-merase chain reaction,The diagnostic value of DKD was analyzed by receiver operating characteristic(ROC)curve.Results The levels of FPG,HbA1c,Scr,BUN,NGAL,UACR,KIM-1 and miR-34a in NC,Nor,Mic and Mac groups increased sequentially(P<0.05).Pearson correlation analysis showed that miR-34a was positively correlated with FPG,HbA1c,Scr,BUN,NGAL,UACR and KIM-1(P<0.01).The area under ROC curve was 0.824,with the sensitivity 75.1%and specificity 86.7%,respectively.Conclusion Plasma miR-34a has certain diagnostic value for DKD.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.