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Background: Environmental and social factors that impact resource allocation in rural, developing regions are key social determinants of health that require multi-sector collaboration to improve health opportunities. Thus, we sought to evaluate the spatial distribution and accessibility of medical resources to assess current disparities, determine best practices for resource allocation, and inform policies to improve regional health planning.Methods: We used the Gini coefficient and agglomeration degree to measure inequality among the frequency distribution of medical resources in Wenzhou, China. We applied the modified hierarchical two-step floating catchment area (H2SFCA) method to evaluate the spatial accessibility of medical institutions across the city. Finally, we explored the influencing factors of accessibility differences using the spearman correlation analysis. Results: The distribution of medical resources in Wenzhou is inequitable according to population and geographical distribution. The overall spatial accessibility of Wenzhou is poor, the accessibility of east region is higher than west region, and the accessibility of different levels of medical institutions varies greatly. Accessibility is positively correlated with the number of institutions (ρ=0.585), the number of doctors (ρ=0.670), population density (ρ=0.769), road density (ρ=0.792), and GDP (ρ=0.310).Conclusions: There are disparities in the spatial and unbalanced distribution of medical resources in Wenzhou. Policies and initiatives to improve the geographical distribution of resources, construct connected road networks, and enhance resident access to medical resources are needed.

Head motion is a major confounding factor impairing the quality of functional magnetic resonance imaging (fMRI) data. In particular, head motion can reduce analytical efficiency, and its effects are still present even after preprocessing. To examine the validity of motion removal and to evaluate the remaining effects of motion on the quality of the preprocessed fMRI data, a new metric of group quality control (QC), dissimilarity of functional connectivity, is introduced. Here, we investigate the association between head motion, represented by mean framewise displacement, and dissimilarity of functional connectivity by applying four preprocessing methods in two independent resting‐state fMRI datasets: one consisting of healthy participants (N = 167) scanned in a 3T GE‐Discovery 750 with longer TR (2.5 s), and the other of chronic back pain patients (N = 143) in a 3T Siemens Magnetom Prisma scanner with shorter TR (0.555 s). We found that dissimilarity of functional connectivity uncovers the influence of participant's motion, and this relationship is independent of population, scanner, and preprocessing method. The association between motion and dissimilarity of functional connectivity, and how the removal of high‐motion participants affects this association, is a new strategy for group‐level QC following preprocessing., Dissimilarity of functional connectivity uncovers the influence of participant's motion, and this relationship is independent of population, scanner, and preprocessing method. Participants with the greatest motion determined the strength of the association between motion and dissimilarity of functional connectivity. A new group‐based quality control strategy is proposed: if a group data set is large enough, participants with large motion in the data set be removed to make the regression slope of the association as flat as possible.

Objective Immune-related adverse events (irAEs) associated with programmed death 1 (PD-1) inhibitor in advanced lung cancer, at home and abroad, have scarcely been reported. We thus aimed to understand the adverse events related to the therapy of nivolumab, a PD-1 inhibitor, in advanced lung cancer, and to provide more experience for the future use of this drug. Methods 34 patients were included in this retrospective study in the Department of Oncology, Jiangsu Cancer Hospital from January 2016 to January 2019, and the adverse immune events were summarized. Results After treatment with nivolumab, irAEs including skin reaction, fatigue, loss of appetite, pneumonia, hypothyroidism, hyperthyroidism, elevated blood alanine aminotransferase (ALT), elevated amylase and decreased platelets and neutrophils were observed or detected, in which the incidences of more than 10% were pneumonia (23.5%), skin reaction (20.6%), fatigue (17.6%), loss of appetite (11.8%), and elevated blood ALT (11.8%). Most of the patients had grade I-II IrAEs, 2 patients with non-small cell lung cancer (NSCLC) developed grade III and IV immune pneumonia, and 1 patient with SCLC developed grade IV cardiotoxicity. The mean PFS of patients with advanced NSCLC was 195.81 ± 36.34 days [95%CI, 124.57~267.05 days] and their mean OS was 541.87 ± 110.80 days [95%CI, 324.70.44~759.03 days] ( Fig. 2 A and B). The objective response rate of patients with NSCLC was19.23% (5/26) and the disease control rate of those was 57.69% (15/26). Conclusion Though the incidence of immune-related adverse events of nivolumab monotherapy is relatively lower and most of them are in grade I-II, attention should be paid to a few serious adverse events that develop rapidly and even endanger life.

Brain functional network properties are globally disrupted in multiple musculoskeletal chronic pain conditions. Back pain with lumbar disk herniation (LDH) is highly prevalent and a major route for progression to chronic back pain. However, brain functional network properties remain unknown in such patients. Here, we examined resting-state functional magnetic resonance imaging-based functional connectivity networks in chronic back pain patients with clear evidence for LDH (LDH-chronic pain n = 146), in comparison to healthy controls (HCs, n = 165). The study was conducted in China, thus providing the opportunity to also examine the influence of culture on brain functional reorganization with chronic pain. The data were equally subdivided into discovery and validation subgroups (n = 68 LDH-chronic pain and n = 68 HC, for each subgroup), and contrasted to an off-site data set (n = 272, NITRC 1000). Graph disruption indices derived from 3 network topological measurements, degree, clustering coefficient, and efficiency, which respectively represent network hubness, segregation, and integration, were significantly decreased compared with HC, across all predefined link densities, in both discovery and validation groups. However, global mean clustering coefficient and betweenness centrality were decreased in the discovery group and showed trend in the validation group. The relationship between pain and graph disruption indices was limited to males with high education. These results deviate somewhat from recent similar analysis for other musculoskeletal chronic pain conditions, yet we cannot determine whether the differences are due to types of pain or also to cultural differences between patients studied in China and the United States.

Background. Both transforaminal percutaneous endoscopic lumbar discectomy with foraminoplasty (TF PELF) and transforaminal percutaneous endoscopic lumbar discectomy without foraminoplasty (TF PELD) were developed for lumbar disc herniation (LDH) patients. However, the safety and effectiveness between the TF PELF and TF PELD have not been investigated. Methods. Of the included 140 LDH patients, 62 patients received TF PELF (PELF group) and 78 patients received TF PELD (PELD group). The operation time, the duration of staying at the hospital, and complication incidences were recorded. All patients were followed up for 2 years, where low back and leg visual analogue scale (VAS) pain ratings and Oswestry Disability Index (ODI) were compared between the 2 groups before and after surgery. Modified Macnab criterion was estimated for all patients at postoperative 2 years. Results. There were no significant difference of the operation time, number of days staying at the hospital, and the incidence of complications between the 2 groups (P>0.05). Two cases in the PELF group and 1 case in the PELD group received a second surgery due to unrelieved symptoms postoperatively. Low back and leg VAS and ODI scores decreased in both groups after operation (P<0.01), respectively, but were not significant between the 2 groups over time (P>0.05). Six patients in the PELF group and 3 patients in the PELD group did not continue the follow-up; thus, only 131 patients completed Macnab evaluation. The satisfactory rate was reported as 80.4% in the PELF group and 90.7% in the PELD group (P>0.05). Conclusions. This study suggested that the safety and effectiveness of TF PELF are comparable to TF PELD for LDH patients.

Both pain rating and exponential model revealed that percutaneous endoscopic lumbar discectomy provided rapid pain recovery that was maintained for at least 3 months compared with conservative treatments., Introduction: Lumbar disc herniation (LDH) is a common back disorder that evokes back and/or leg pain. Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive surgery for patients with LDH. However, there is little evidence of effectiveness of PELD compared with conservative treatments. Objective: The goal of this study was to quantify the efficacy of PELD compared with conservative treatments. Methods: Here, we conducted a prospective observational cohort study using momentary pain assessments via a smartphone app during 3 months following surgery. The trajectories of daily ecological momentary pain assessments were fitted with an exponential model containing two parameters: a pain reduction coefficient and the percentage of persistent pain. To control for selection bias between PELD and Conservative groups (N = 167 and 34), we used inverse probability (IP) of treatment weighting for statistical comparisons. Results: Compared with conservative treatments, both momentary pain rating and the exponential model showed statistically significant pain recovery following PELD (p < 0.001). In addition, PELD had a faster pain recovery rate (hazard ratio (95% confidence interval): 1.75 (1.40, 2.20), p < 0.001), greater overall pain recovery rate (odds ratio (95%CI): 2.35 (2.01, 5.26), p < 0.001), faster pain reduction (t199 = 3.32, p = 0.001), and lower estimated persistent pain (Z = 2.53, p = 0.011). Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Conclusions: In conclusion, momentary pain rating and the model fitting revealed that PELD provided rapid pain recovery that lasted for at least three months. Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Daily momentary pain rating on a smartphone may be able to provide more informative data to evaluate effect of an intervention than pain assessment on hospital visits.

This paper presents a new version Java code for the three-dimensional simulation of Cluster–Cluster Aggregation (CCA) model to replace the previous version. Many redundant traverses of clusters-list in the program were totally avoided, so that the consumed simulation time is significantly reduced. In order to show the aggregation process in a more intuitive way, we have labeled different clusters with varied colors. Besides, a new function is added for outputting the particle’s coordinates of aggregates in file to benefit coupling our model with other models. New version program summary Program Title: CCA v04 Program Files doi: http://dx.doi.org10.17632/zwz37tvjny.1 Licensing provisions: Apache-2.0 Programming language: Java Journal reference of previous version: Computer Physics Communications 207 (2016) 547–548 Does the new version supersede the previous version?: Yes Nature of problem: The previous program for CCA model can be optimized for yielding better operation efficiency and visualization effects. Besides, it can be extended for coupling with other models by adding some new functions. Solution method: Some redundant traverses of the clusters-list for updating an important variable were removed technically. Furthermore, displaying different clusters with distinct colors can benefit to the effectiveness of visualization. We have also introduced a new function for outputting the aggregated clusters, so that this model can be easily coupled with other models. Reasons for the new version: 1. In the previous versions [1–3], the global variable of D m a x , which means the maximum diffusion coefficient of clusters, is supposed to be calculated when aggregation occurs. In fact, this variable is critical to determine whether the currently selected cluster carries out diffusion or not. In the previous version, we had to traverse the clusters-list to update D m a x , even though it may keep unchanged after a round of aggregation. But, we have explored that it is not necessary to traverse all clusters, if we compare the previous variable of D m a x with the diffusion coefficient of the new cluster, which is formed by aggregating two clusters. In the case of the new one is larger, D m a x will be updated to it; otherwise, D m a x keep unchanged. Obviously, removing redundant traverses can enhance algorithm efficiency, and the time complexity of the algorithm is closely related to the loop in it. As a result, the new version of code can greatly cut down the simulation time, in contrast to the previous codes. 2. The old versions paint all particles with same color, which does not help to identify different clusters. In order to show the visualization of the 3D aggregate process in different states intuitively, we introduce labeling different clusters with different colors. Consequently, the particles belong to one cluster are painted with the same color. 3. A new function is added to record intermediate or final state of clusters so that it can be used for further research when using other relevant models. Summary of revisions: 1. Reduce unnecessary traverses of the clusters-list for speeding up simulation. 2. Paint clusters with different colors to pursuit better visualization effects. 3. Add a new function of exporting the coordinates of clusters to a text file for benefiting other models. Additional comments: To test the optimization effects offered by the new version of code, we have carried out a comparison experimentto measure the simulation time with different initial particles, by using the new and the previous version 3.0 of code. In the experiments, we set concentration C to 0.01, diffusion exponent γ to 0, sticking probability exponent σ to 1, the sticking probability P 1 to 0.1, absolute temperature T to 298 K, and the side length L of cube was respectively set to 30, 40, 50, 60, 70 and 80 to yield different initial particles, as the number of particles N can be calculated by the formula N = C ∗ L 3 [1]. To avoid the influences of hardware and software, we use Monte Carlo steps (MCS) as our simulation time [4–6]. As shown in Fig. 1 , the slope coefficient caused by this new version of code is about 1.3813, it is close to line complexity, as for the previous version, it is 1.5703, larger than the new one. It is obvious the new one has a faster running speed than the previous one. More importantly, the reduction of simulation time becomes more obvious when the number of simulated particles is getting larger. The changed visualization of our program is shownin Fig. 2 . We can clearly see how much clusters in simulation system, and how they distribute. And the button “save” marked red in Fig. 2 can help realize our new function by exporting the particle coordinates to a text file, which also store the related initial conditions. Acknowledgments This work was partially supported by “ National Natural Science Foundation of China (Nos. 41271292 , 61303038 )”. References [1] C. Li, H. Xiong, 3D simulation of the Cluster-Cluster aggregation model, Computer Physics Communications 185 (12) (2014) 3424–3429. [2] K. Zhang, H. Xiong, C. Li, A new version of code Java for 3D simulation of the CCA model, Computer Physics Communications 204 (2016) 214–215. [3] K. Zhang, J. Zuo, Y. Dou, C. Li, H. Xiong, Version 3.0 of code Java for 3D simulation of the CCA model, Computer Physics Communications 207 (2016) 547–548. [4] T. Vicsek, Dynamic scaling for aggregation of clusters, Physical Review Letters 52 (19) (1984) 1669–1672. [5] P. A. Netz, D. Samios, The study of network formation as a cluster-cluster diffusion-limited aggregation process: Modelling of the curing of an epoxy-resin using the Monte Carlo method, Macromolecular Theory Simulations 3 (3) (1994) 607–621. [6] H. Xiong, H. Li, W. Chen, L. Wu, Data structure for on-lattice cluster-cluster aggregation model performance optimization, Computer Physics Communications 185 (3) (2014) 836–840.

Hydrolytic degradable PBT/PEG copolymer was synthesized by macromolecular transesterification method from PBT and PEG macromonomers. The resultant copolymers were characterized by (1)H-NMR and GPC. The non-isothermal crystallization behavior of these copolymers was studied by differential scanning calorimetry (DSC). The water absorption and hydrolytic degradation behavior of PBT/PEG copolymers were also studied in detail.

Vesicular stomatitis virus (VSV) matrix protein (MP) has been reported to be capable of inducing apoptosis in vitro in the absence of other viral components. In the present study, the antitumor effect of a recombinant plasmid encoding VSVMP on human ovarian cancer and its apoptosis-inducing efficacy in vivo were further investigated.The recombinant plasmid DNA carrying VSVMP-cDNA (VSVMP-p) was constructed. SKOV3 ovarian cancer cells were transfected with VSVMP-p and examined for apoptosis by Hoechst 33258 staining and flow cytometric analysis. For in vivo study, intraperitoneal ovarian carcinomatosis models in nude mice were established and randomly assigned into four groups to receive six twice-weekly i.p. administrations of VSVMP-p/liposome complexes, empty plasmid/liposome complexes, liposome alone or 0.9% NaCl solution, respectively. The weight of intraperitoneal carcinomatosis and the survival were monitored. Tumor tissues were inspected for apoptosis by TUNEL and Hoechst-33258 assay.Plentiful apoptosis were observed in SKOV3 cells transfected with VSVMP-p. VSVMP-p reduced intraperitoneal tumor weight by about approximately 90% compared with control agents (p0.01) and significantly prolonged the survival of tumor-bearing mice (p0.05), with in vivo apoptosis index of 12.6+/-2.7% which was much higher than that of control groups (4%) (p0.05). Interestingly, this antitumor effect was accompanied by a noticeable NK cell accumulation. The treatment with VSVMP-p was devoid of any conspicuous toxicity.These observations suggest that VSVMP-p have strong antitumor effects by inducing apoptosis and possibly NK cell-mediated tumor resistance mechanisms, and it may be a potentially effective novel therapy against human ovarian cancer.

In this article, a pH sensitive semi-interpenetrating network (SIPN) hydrogel based on methacrylic acid, BSA, and PEG was prepared by UV initiated free radical polymerization. The swelling behavior and pH sensitivity of these hydrogels were studied in detail. With the increase in pH of the aqueous solution from 1.7 to 9.23, the swelling ratio of these hydrogels increased accordingly. The effect of BSA and crosslinker (BIS) content on the swelling behavior was more complicated, and the results were shown in the text.

In this paper, biodegradable aliphatic copolyesters were synthesized from e-caprolactone, adipic acid, and 1,6-hexanediol by melt-polycondensation method. The chemical structure, and thermal properties of these copolymers were studied in detail. The water absorption behavior and hydrolytic degradation behavior of this copolyester were also studied. This aliphatic copolyester prepolymer would be used to prepare the biodegradable poly(ester urethane), which might have potential application in biomedical field.

In this article, a new kind of biodegradable polyetheresteramide-based polyurethane (PEEA-U) copolymers were prepared by the melt polycondensation method from ϵ-caprolactone, 6-aminocaproic acid, poly(ethylene glycol), and toluene diisocyanate. The water absorption of PEEA-U was affected strongly by the reaction time and the content of chain extender; and the hydrolytic degradation behavior of the copolymers was mainly determined by the reaction time, chain extender content, and the pH value of the degradation medium. Also, DSC, 1H-NMR, and inherent viscosity were used to characterize the degradation behavior of the copolymers. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005

Biodegradable PBT/PEG copolymers were synthesized by macromolecular transesterification method, and were characterized by 1H-NMR and DSC. Alkaline degradation behavior was studied too. Indirubin loaded microspheres were prepared by O/W solvent evaporation method.

CCL19 [chemokine (C-C motif) ligand 19; also known as MIP-3beta (macrophage inflammatory protein-3beta) or ELC (Epstein-Barr-virus-induced molecule 1 ligand chemokine)], one of the immunostimulatory cytokines, chemoattracts both DCs (dendritic cells) and T-lymphocytes. Adenoviral vector is one of the most used gene delivery vectors for cancer therapy because of its high gene-transfection efficiency. However, its wider application is limited, owing to immune responses that reduce transgene expression and decrease the efficacy of repeated administration. We constructed the recombinant replication deficient adenoviral vectors containing the CCL19 gene (Ad-CCL19) and combined them with PEG-PE [poly(ethylene glycol)-phosphatidylethanolamine]-modified cationic liposomes (Ad-CCL19/PEG-PE) for immunotherapy against murine fibrosarcoma. Although there were hardly any therapeutic differences between Ad-CCL19- and Ad-CCL19/PEG-PE-treated mice that were observed at the second administration, the final results demonstrated that Ad-CCL19/PEG-PE-treated mice survived much longer. The antitumour efficacy may be related to the high level of CCL19 after the final administration and lasting expression of IFN-gamma (interferon-gamma) and IL-12 (interleukin-12) in the Ad-CCL19/PEG-PE-treated group, which were measured by reverse-transcription PCR and ELISA. The results demonstrated that PEG-PE-cationic-liposome-conjugated adenovirus could prolong the expression of the therapeutic gene in vivo and may enhance the antitumour efficacy.