OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin， and provide data support for the enhancement of relevant policies. METHODS In this research， the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin （October-December 2021 and October-December 2022）， and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost （DDDc） of various types of insulins. The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated， using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income （i.e. the proportion of annual expenditure） as an indicator. RESULTS After the specialized centralized procurement， DDDc of various types of insulins decreased by 20.7%-71.8%， with an average reduction of 45.7%. Moreover， the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin. The reduction in the proportion of annual expenditure on insulin ranged from 24.3% to 73.4%， with an average decrease of 48.5%. Premixed insulin analogs experienced the greatest reduction （73.4%）. Following the specialized centralized procurement， DDDc of insulin decreased in all provinces. Except for Guangxi （10.2%）， the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%. CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability， thereby alleviating the economic pressure on patients with diabetes. There are notable cost disparities among provinces and among insulin categories， which require attention.

Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

This article reports a rare case of proliferative glomerulonephritis with monoclonal immunoglobulin deposits. The patient, a middle-aged woman, exhibited clinical manifestations including nephrotic syndrome, microscopic hematuria, renal insufficiency, hyperglycemia, and bilateral diabetic retinopathy. Notably, monoclonal bands were absent in both blood and urine immunofixation electrophoresis. Renal biopsy revealed membranoproliferative glomerulonephritis, with immunofluorescence revealing exclusive petal-like deposition of IgG3 subtype along the capillary loop. Electron microscopy demonstrated segmental thickening of the glomerular basement membrane, along with electron dense deposits in the subendothelial and mesangial areas, lacking discernible substructure. The diagnosis comprised proliferative glomerulonephritis with monoclonal immunoglobulin deposition concurrent with diabetic nephropathy. Subsequent sequential treatment with daratumumab and cyclophosphamide over 6 months led to partial remission of nephrotic syndrome, normalization of renal function, and significant improvement of anemia. During the 24-month follow-up period, no serious adverse reactions occurred.

Objective To observe the value of deep learning combine with radiomics based on MRI for evaluating H3 K27 status of midline gliomas.Methods Totally 127 patients with diffuse midline glioma H3 K27-altered(H3-DMG)and 127 patients with midline glioblastoma(GBM)without H3 K27 mutation were retrospectively enrolled.The patients were randomly divided into training set(n=204)and test set(n=50)at the ratio of 8:2.U-Net neural network visual and radiomics features of tumors were extracted based on MRI,and a deep learning radiomics model was established,its value for evaluating H3 K27 status was observed.Results Based on training set,0.500 was obtained as the security score partition value for the model classification task.In test set,the median safety score of the obtained deep learning radiomics model for evaluating H3 K27 status of H3-DMG and GBM was 0(0,0)and 0.999(0.616,1.000),respectively,for the former was lower than for the latter(Z=-5.114,P＜0.001).The sensitivity,specificity,accuracy and area under the curve of deep learning radiomics model for evaluating H3 K27 status in training set was 93.14％,81.37％,87.25％and 0.953(95％CI[0.923,0.976]),respectively,while was 88.00％,80.00％,84.00％and 0.922(95％CI[0.829,0.986])in test set,respectively.Conclusion Deep learning radiomics based on MRI could accurately evaluate H3 K27 status of midline gliomas.

OBJECTIVE: To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. METHODS: The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. RESULTS: Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. CONCLUSION TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.
Humans ; Fracture Healing/physiology* ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic ; Fractures, Bone ; Osteogenesis

Background Tuberculosis is the most common complication of pneumoconiosis, which accelerates the progression of pneumoconiosis. Pneumoconiosis combined with tuberculosis is a major health risk. Objective To understand the outpatient health service utilization for patients of pneumoconiosis combined with tuberculosis and its main influencing factors. Methods A stratified random sampling combined with non-random sampling was used to select 11181 pneumoconiosis patients in 27 provincial administrative regions (excluding Shanghai, Tianjin, Hainan, Tibet Autonomous Region, Taiwan, Hongkong and Macao Special Administrative Regions) from December 2017 to June 2021. A self-constructed questionnaire, i.e. Health Seeking Behaviors of Pneumoconiosis Patients and Their Influencing Factors, was used, which included basic information, outpatient and inpatient service utilization, and influencing factors of medical treatment behaviors of pneumoconiosis patients. The effective recovery rate of the questionnaire was 90.7%. All patients of pneumoconiosis combined with tuberculosis (n=762) were included as the study subjects. The difference of outpatient utilization in the past two weeks, choosing medical institutions, and the reasons of not seeking medical treatment between urban and rural areas, and the influencing factors of outpatient service utilization were analyzed. Results The study subjects were mainly silicosis combined with tuberculosis (502 cases, 65.9%) and coal workers' pneumoconiosis combined with tuberculosis (232 cases, 30.5%), aged (58.6±12.5) years old. The main region was Western China (45.1%), followed by Eastern China (22.1%), Centeral China (20.2%), and Northeastern China (12.6%). The outpatient utilization rate in the past two weeks was 38.5% (293/762), and the main medical institutions consulted were municipal or provincial hospitals (32.0%), district or county hospitals (28.6%), and township hospitals or health service centers (17.5%). Short distance (20.7%), the availability of specialist outpatient services (16.7%), high level of medical care (14.8%), and low medical cost (12.3%) were the main reasons in choosing medical institutions. Higher proportion of patients seeking medical services due to acute exacerbation in rural areas was reported than in urban areas in the past two weeks (P<0.01). In addition to being hospitalized (113 cases, 41.4%) and self-purchasing medicine (46 cases, 16.8%), the reasons for not seeking medical treatment were self-perceived mild symptoms (15.0%) and high medical cost without reimbursement (9.5%). The multiple regression results showed that outpatient rate for patients of pneumoconiosis combined with tuberculosis in the western region was higher than that in the eastern region (OR=1.66, 95%CI: 1.03, 2.68); patients with an annual personal income of 10000-35500 yuan had a higher outpatient rate than the > 35500 yuan income group (OR=2.54, 95%CI: 1.49, 4.36); the outpatient rate of silicosis patients was higher than that of coal workers' pneumoconiosis (OR=1.83, 95%CI: 1.23, 2.72); the outpatient rate of patients with clinically diagnosed cases (no classified stage of pneumoconiosis) was higher than that of patients with stage I pneumoconiosis (OR=2.32, 95%CI: 1.24, 4.31). Exacerbation of pneumoconiosis-related symptoms in past two weeks (OR=4.26, 95%CI: 2.89, 6.28), occupational injury insurance (OR=0.49, 95%CI: 0.30, 0.80), and hospitalization in past one year (OR=2.37, 95%CI: 1.41, 3.97) were the main factors influencing the outpatient health service utilization among patients of pneumoconiosis combined with tuberculosis. Conclusion The outpatient rate of patients of pneumoconiosis combined with tuberculosis is higher than that of patients of pneumoconiosis without tuberculosis. The utilization of outpatient services is related with disease factors and socio-economic security factors.

BACKGROUND:The remediation and treatment of bone defects present considerable challenges,with a variety of clinical intervention strategies available.One such approach,the Masquelet technique,has demonstrated high rates of success and reliable outcomes and is currently employed in clinical practice.However,the underlying mechanisms of this technique remain incompletely understood,and certain challenges persist in its clinical application,indicating that this technique is not yet fully mature. OBJECTIVE:To compile and categorize the biomaterials currently employed in research aimed at improving the Masquelet technique,in order to provide insights and references for the further development of this technique. METHODS:A literature search of the China National Knowledge Infrastructure and PubMed databases was conducted,spanning publications from January 2013 to November 2022.The search terms used included"Masquelet technique;induced membrane technique;induced membrane;biomaterial;bone defect"in both Chinese and English.A total of 58 articles meeting the inclusion criteria were reviewed. RESULTS AND CONCLUSION:(1)The emergence and continual development of the Masquelet technique provide a therapeutic strategy for treating bone defects.Some researchers are focusing on developing superior spacer materials,autograft substitutes,and membrane materials that mimic the properties of the induced membrane,to simplify the two-stage procedure,shorten treatment duration,and reduce patient distress.(2)Calcium sulfate,silicone,poly(lactic-co-glycolic acid),and polypropylene can replace polymethylmethacrylate bone cement to form induced membranes in animal experiments or clinical applications,each with their advantages.Contrary to expectations,common materials such as titanium and polyvinyl alcohol sponge cannot replace polymethylmethacrylate bone cement.(3)Autograft substitutes are diverse,with allograft bone,β-tricalcium phosphate,absorbable gelatin sponge,α-calcium sulfate hemihydrate,bioactive glass,titanium,and tantalum demonstrating their ability to reduce the quantity of autologous cancellous bone graft required in the second stage of the procedure.Among them,allograft bone,β-tricalcium phosphate,bioactive glass,titanium and tantalum can replace autogenous bone as grafts,and other materials need to be mixed with autogenous bone,in both clinical and fundamental experiments.(4)Biomimetic-induced membranes,human amnion,human decellularized dermis,polytetrafluoroethylene,and even autogenous cortical bone have been shown to possess properties similar to the induced membrane.(5)Most of the application and research of biomaterials in this technology still exist in the stage of basic research and have not been applied in clinical practice or popularized on a large scale,but the above materials can provide more sufficient theoretical basis and new ideas for the exploration of Masquelet technical mechanism,the improvement of surgical methods and clinical application.

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.