ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L^-1 cisplatin）， SMI group （20 g·L^-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.

Objective To investigate the current distribution of radiotherapy resources in Gansu Province, evaluate the equity of resource allocation, and provide a scientific basis for optimizing regional resource allocation. Methods A questionnaire survey was carried out to assess radiotherapy resources in medical institutions across Gansu Province, China. The equity of radiotherapy resource distribution and associated disparities were assessed using the Gini coefficient, Lorenz curve, and Theil index. Results A total of 23 medical institutions in Gansu Province provided radiotherapy services, comprising 39 radiotherapy devices and 438 professionals, of whom medical physicists accounted for 16.9%. The radiotherapy frequency was 0.47 cases per thousand population. The Gini coefficients for radiotherapy resource distribution ranged from 0.38 to 0.56 by population and from 0.52 to 0.70 by geography. The Theil index for radiotherapy resources ranged from 1.36 to 3.67. Conclusion Radiotherapy resources in Gansu Province were insufficient, and the capacity of radiotherapy service was suboptimal. The equity of radiotherapy resource allocation by geography was worse than that by population. Therefore, it is imperative to address the shortage of radiotherapy resources, strengthen the professional workforce, enhance the capacity radiotherapy service and resource utilization, optimize resource allocation, and promote regional equity in radiotherapy provision in Gansu Province.

Objective To address the current blind spots in quality control and the risk of data distortion in radiological health technical service institutions, overcome the limitations of low efficiency and insufficient anomaly identification in manual verification, establish an automatic anomaly early warning mechanism based on AI algorithms, provide accurate clues for health supervision and law enforcement, and significantly enhance the efficiency of industry supervision. Methods On-site inspection data were collected via photographic imaging. Advanced image processing and object detection algorithms were employed to automatically extract and analyze key information from the images. Through data analysis, the system was used to calculate and assess the inspection results. A dynamic early warning engine was developed to automatically trigger alerts upon detection of deviations from standard thresholds or regulatory violations in radiological health technical services. These alerts were delivered through a regulatory information system. Results Following AI model training, the accuracy of the image processing and object detection algorithms reached 99% and the early warning accuracy reached 93%. Compared with the traditional supervision mode, the efficiency of anomaly detection was improved and the average response time was shortened. Conclusion The full-process supervision information system constructed in this study has realized the triple mechanism of pre-event standardization, in-event monitoring, and post-event traceability for radiological health technical services. In particular, the system has established a four-level quality control chain of “institutional self-inspection, intelligent recheck, expert judgment, and administrative action”, providing a technological innovation path for ensuring the radiation protection and safety of medical staff, patients, and the public.

Chemotherapy is an important treatment for tumors， but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine （TCM） has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors， such as cold-natured （e.g. Scutellaria baicalensis， Rhus chinensis）， cool-natured （e.g. Ligustrum lucidum， Ophiopogon japonicus）， warm-natured （e.g. Panax ginseng， Epimedium brevicornu， Curcuma longa， Angelica sinensis）， hot-natured （e.g. Cinnamomum cassia， Aconitum carmichaeli）， and neutral-natured （e. g. donkey-hide gelatin， Lycium barbarum， Rhodiola rosea， fungi）， can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells， improving the bone marrow hematopoietic microenvironment， inhibiting the oxidative stress response， regulating signaling pathways， so as to ultimately repaire inflammatory damage and improve hematopoietic function， thereby playing an anti-myelosuppressive role.

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.

Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidogenic,aciduric,and biofilm-forming capabilities.Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents.The current study represents an up-to-date review of in silico approaches of drug design against dental caries,which have emerged more and more powerful complementary to biochemical attempts.Firstly,we categorize the in silico approaches into computer-aided drug design(CADD)and AI-assisted drug design(AIDD)and highlight the specific methods and models they contain respectively.Subsequently,we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S.mutans,such as glucosyltransferases(Gtfs),antigen Ⅰ/Ⅱ(AgⅠ/Ⅱ),sortase A(SrtA),the VicRK signal transduction system and superoxide dismutases(SODs).Finally,we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.