ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

OBJECTIVE To establish a multi-dimensional value assessment framework for new antidiabetic drugs based on multi-criteria decision analysis theory， thus providing a theoretical framework and methodology for evidence-informed medical insurance decision-making. METHODS Firstly， multi-dimensional evidence was searched and obtained to provide reliable data for the establishment of the framework. Secondly， in terms of the obtained evidence， the value assessment framework was preliminarily constructed. Its structure， main core criteria， and contextual criteria were determined through focus group discussion. Finally， the criteria and sub-criteria of the framework and their weights were further determined， reasons for inclusion of sub-criteria and the reasonableness of rating scores were evaluated， and methods of assessment were optimized through expert consultation. RESULTS The multi-dimensional value assessment framework for new antidiabetic drugs was composed of core criteria and contextualized criteria， which could be used for quantitative and qualitative value assessment of new drugs， respectively. The core criteria consisted of five dimensions， with affordability （6.31） having the highest weighting score， followed by comparative effectiveness （6.20）， comparative safety （6.01）， cost-effectiveness （5.89）， and quality of evidence （5.46）. After the normalization of weight within sub-criteria， the budget impact on medical insurance had the highest standardized weight， followed by the control of glycated hemoglobin and patient affordability. The contextual criteria included two dimensions， i. e.， innovation and equity. CONCLUSIONS The assessment framework integrates evidence， stakeholders’ values， and decision contexts to enable a multi- dimensional and evidence-based assessment of the value of new antidiabetic drugs.

Congenital tooth agenesis is a type of craniofacial developmental anomaly with reduced number of teeth, which is caused by disturbances in tooth germ development. If the number of missing teeth is less than six (excluding the third molars), it is termed as hypodontia. The second premolars are most commonly affected. When the second premolars are missing, the second primary molars are more prone to suffer from retention, infraocclusion, caries, pulpitis, or periapical periodontitis. Without timely prevention and appropriate treatment, congenital loss of second premolars may cause adverse effects on the patients′ tooth arrangement, occlusal function, craniofacial development, and even future prosthetic treatment. This review summarises the aetiological and diagnostic features of the agenesis of second premolars, and discusses the clinical considerations of retaining or extracting the second primary molars without permanent tooth germs, when the absence of permanent tooth germs is fully established or not, so as to provide references for dentists.

Objective:To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion.Methods:A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t-test, Mann-Whitney U test, Wilcoxon signed rank test, χ2 test or corrected χ2 test as appropriate. Results:Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes; t=-2.392, P=0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t=10.604, P<0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days; t=2.480, P=0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups ( χ2=0.278, P=0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups ( t=1.607, P=0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups ( t=-1.003, P=0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was ( M(IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences ( Z=-3.937, P<0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ2=1.765， P=0.184). Conclusion:3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

In this paper， we systematically sorted out and verified the name， origin， producing area change， quality， efficacy and processing of Halloysitum Rubrum by consulting materia medica， medical books， prescription books from past dynasties， and modern literature， and combined with the comprehensive analysis of trait identification， hygroscopicity measurement and X-ray diffraction（XRD） detection， in order to provide a basis for understanding the original source of the mineral medicine. The results indicated that Halloysitum Rubrum was first contained in the Shennong Bencaojing， it had been consistently named Chishizhi， there were also aliases such as Chifu， Hongxinshi and Chiyouzhi. The description of Halloysitum Rubrum in ancient materia medica aligns with modern findings， categorizing it under the silicate kaolinite family， specifically polyhydrous kaolinite， with associated minerals mainly being dickite， nacrite， hematite， gibbsite， mica， etc. Historically， the production area of Halloysitum Rubrum was mainly located in the Qinling Mountains， Shandong and Henan， and is now primarily distributed in most parts of China， including Henan， Hubei and other provinces. Quality evaluation in ancient times included descriptions like "fresh and greasy color"， "delicately sticky tongue and lips" and "smooth as fat". Modern materia medica mostly evaluates its quality based on color， luster， texture and hygroscopicity， noting characteristics such as red color， smoothness， delicacy， softness and strong viscosity. Halloysitum Rubrum is sweet， sour and pungent in flavor， warm in nature， non-toxic， and belongs to the heart and large intestine meridians. It acts as an astringent and solidifying agent， particularly useful in the treatment of long-term dysentery and diarrhea， common processing methods include fire calcination， water flying， and vinegar quenching. Comprehensive analysis of the traits， XRD and humidity absorption of different batches of samples showed that the commercially available Halloysitum Rubrum is mainly bright red or brownish red， with a smooth surface like grease， soft and smooth texture， delicate cross-sectional texture， and some have waxy luster and strong water absorption. It is mainly composed of 10 Å（1 Å=0.1 nm） polyhydric kaolinite， and is often accompanied by 7 Å polyhydric kaolinite， nacrite， etc. Genuine products tend to have higher moisture absorption than counterfeit ones， which can be used as a key indicator to distinguish the authenticity. The quality evaluation of Halloysitum Rubrum aligns with historical materia medica， where "fresh color， delicate and greasy lips" could serve as a key feature for its quality evaluation.

By reviewing the historical materia medica， medical books and modern literature， this paper has systematically sorted out and verified the name， origin， quality and other aspects of Ophicalcitum. After herbal textual research， it is shown that before the Qing dynasty， the mineral medicine was mostly recorded in the name of Huarushi， but now it is called Huaruishi， and there is another mixed name Baiyunshi. The light white spots described in the historical materia medica are consistent with the characteristics of marble with sparkling star-like luster， combined with the color like sulfur， color are green， black spots and other serpentine features， it is deduced that it is serpentine marble， consistent with the present-day Ophicalcitum， and Ophicalcitum in the Song dynasty has a high content of serpentine. The main producing areas are Henan， Shaanxi， Shanxi and Sichuan， Jiangsu， Zhejiang， Hebei and other places are also available. Successive generations of materia medica on the quality evaluation of Ophicalcitum is less， the modern to neat and firm in the texture， sandwiched with yellow-green mottled for the best. Ophicalcitum is acidic， astringent and neutral in nature， belonging to the liver meridian， with the efficacy of treatment of gold sores and blood flow， internal leakage of cataracts， dropping afterbirth， now describing its efficacy as removing blood stasis and stopping bleeding. In ancient times， the earliest processing method was burning， followed by calcination by sulphur， calcination， quenching with vinegar and other methods. In modern times， it has been simplified to open calcination， processing with vinegar and the addition of water quenching. The gravimetric method and ethylenediaminetetraacetic acid titration were used to detect the contents of CO₃^2- and CaCO₃ in Ophicalcitum， respectively， and it was found that the gap in CaCO₃ content among commercially available products was wide， and the content of CaCO₃ in sample S13 and sample S18 was the same， but their compositions were different， and according to the contents of CO₃^2- and CaCO₃， the dolomite and calcite contents could be calculated， of which the higher the calcite content the more obvious the sparkling star-like luster. Raman spectroscopy and X-ray diffraction（XRD） were used to detect the physical phase composition of the powder of the samples， and Raman spectroscopy was used for the rapid non-destructive testing of the striped part， which showed that Ophicalcitum was mainly composed of dolomite， calcite， serpentine， olivine and pyroxene， with serpentine dominanting the striped part. In summary， the 2020 edition of Chinese Pharmacopoeia stipulates that the content of CaCO₃ in Ophicalcitum is not less than 40%， which is difficult to control its quality， and it is suggested to increase the detection of CO₃^2- content. This study can provide a scientific basis for the traceability of Ophicalcitum and better guide the clinical medication and rational utilization of resources.

Purpose/Significance Taking Jiashan county's chronic disease management mode based on blockchain as an example,new strategies for chronic disease management under the integrated county medical community mode are discussed.Method/Process U-sing the PEST-SWOT analysis method,the paper analyzes the strengths,weaknesses,opportunities and threats of the chronic disease management mode based on blockchain in Jiashan county from 4 aspects:politics,economy,society,and technology.Result/Conclu-sion The chronic disease management mode based on blockchain technology can ensure seamless connection and sharing of data,guaran-tee the security and traceability of patients'personal information and health records,and promote the common development of blockchain technology and chronic disease management in Jiashan county.