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.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective·[18F]F-FMISO and[18F]F-FLT are specific PET imaging agents for detecting the hypoxia microenvironment and cell proliferation,respectively.This study aims to visualize and monitor the impact of drug resistance in pancreatic cancer on the hypoxia microenvironment and cell proliferation through[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging,with the goal of providing a theoretical basis for clinical application.Methods·The CCK-8 assay was conducted to assess drug resistance in the PANC-1/R(PR)pancreatic cancer cell line compared to the parental PANC-1(P)cell line.Subcutaneous xenograft models of pancreatic cancer were established by injecting male BALB/c nude mice with pancreatic cancer cells into the left axillary subcutaneous region.Subgroups were treated with gemcitabine(GEM)chemotherapy starting on day 18(18D-G group)or day 12(12D-G group)after inoculation of tumor cells.[18F]F-FMISO and[18F]F-FLT PET/CT imaging were performed before and after treatment to obtain semi-quantitative parameters(maximum standardized uptake value,SUVmax).ΔSUVmax was calculated by using the following equation:ΔSUVmax=(SUVmax of second imaging-SUVmax of first imaging)/SUVmax of first imaging.Receiver operating characteristic(ROC)curves were used to determine the optimal threshold for the semi-quantitative parameters to assess pancreatic cancer drug resistance.Results·The CCK-8 assay confirmed that the PR cells exhibited high resistance to GEM,with a resistance index of 4.24(n=5).In vivo experiments showed that GEM chemotherapy significantly inhibited tumor growth and prolonged survival in the parental pancreatic cancer group(12D-G group,P=0.025),whereas GEM chemotherapy accelerated tumor growth and shortened survival(18D-G and 12D-G,P=0.025)in the drug-resistant pancreatic cancer group.In addition,in the non-chemotherapy group,ΔSUVmax-FLT might be negatively correlated with survival time,while in the chemotherapy group,both ΔSUVmax-FMISO and ΔSUVmax-FLT were negatively correlated with survival time(P=0.050,P=0.006).In the 18D-G and chemotherapy group,the second imaging showed significantly lower ΔSUVmax-FMISO and ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.045,P=0.050).In the 12D-G and chemotherapy group,the second imaging showed slightly lower ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.051).ROC analysis identified the optimal threshold for assessing pancreatic cancer drug resistance:when ΔSUVmax-FLT=0.45 in the non-chemotherapy group,the sensitivity and specificity were 100.00%and 50.00%,respectively;when ΔSUVmax-FMISO=0.37 and ΔSUVmax-FLT=0.36 in the chemotherapy group,the sensitivity and specificity were 100.00%and 83.33%,respectively.Conclusion·[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging can be used to assess drug resistance in pancreatic cancer.The comparison of[18F]F-FMISO and[18F]F-FLT PET differences before and after chemotherapy provides the most accurate prediction of drug resistance and survival time.

Peripheral nerve injury (PNI) is one of the most common issues among trauma patients.Treatment strategies for PNI typically involve surgical repair,rehabilitation therapy and medication management,but may still not achieve the expected therapeutic outcome. Following nerve injury,Schwann cells clear cellular debris,release growth-promoting factors and provide guidance support that promotes the regrowth of damaged nerve fibersand its reconnection to target tissues. The release of transforming growth factor beta (TGF-β) to the injury site after PNI can induce the transformation of astrocytes to an A2 phenotype,thereby upregulating the expression of neurotrophic factors. Meanwhile,TGF-β can initiate a series of phenotypic changes in Schwann cells,modulate immune cells,and activate the innate growth potential of neurons,thereby enhancing nerve regeneration potential. TGF-β can also promote angiogenesis,maintain the integrity of the blood-nerve barrier and enhance its permeability,thereby providing a beneficial microenvironment for nerve regeneration by inhibiting inflammation. This paper reviews the potential roles of TGF-β in peripheral nerve regeneration and investigates the underlying mechanisms,in order to provide new insights for better treatment of PNI.

Alzheimer's disease(AD)is the most common neurodegenerative disorder leading to dementia in the elderly,characterized by a gradual decline in cognitive function and daily living abilities.The pathogenesis of AD remains unclear,and the efficacy of existing pharmacological treatments is limited,making the search for new therapeutic approaches imperative.Current research suggests that transcranial alternating current stimulation(tACS)can ameliorate cognitive deficits in AD,potentially due to its ability to modulate single or nested brain rhythms,local or distant synchronization,and metabolic activity,which can influence cognitive functions.This review summarizes the research progress of tACS in the treatment of AD,aiming to provide new insights into the exploration of the pathogenesis and treatment of AD.

Objective To study the expression levels and clinical significance of histone H3 trimethylation at lysine 4(H3K4me3),histone H3 trimethylation at lysine 27(H3K27me3)and modifying enzyme in placental tissue of patients with premature rupture of membranes(PROM)with chorioamnionitis.Methods Clinical data of 95 pregnant women treated in the Xi'an Gaoxin Hospital due to PROM from June 2021 to December 2023 were retrospectively collected,and they were divided into infected group and a non-infected group according to whether they were complicated with histological chorioamnionitis(HCA).Another 30 normal pregnant women were selected as the control group.Placental tissues of all subjects were collected and H3K4me3 and H3K27me3 levels were detected,and the expression levels of H3K4me3,H3K27me3 specific methyltransferase[mixed lineage leukemia protein-1(MLL1),Zeste enhancer homolog 2(EZH2)]and demethyltransferase[lysine-specific demethylase 5B(KDM5B),Jumonji domain-containing protein 3(JMJD3)]were detected by quantitative real-time PCR(qRT-PCR).The expression differences of H3K4me3,H3K27me3 and specific modifiers among the three groups and the correlation with the histological stage of HCA were analyzed.The Receiver operating characteristic curve(ROC)was plotted,the Area under curve(AUC)value was calculated,and H3K4me3 was evaluated.Predictive value of H3K27me3 for concurrent HCA infection.Result Compared with the control group,the levels of H3K4me3(0.08%±0.02%,0.12%±0.03%vs 0.25%±0.06%),MLL1 mRNA(1.32±0.16,1.44±0.23 vs 2.02±0.31),and JMJD3 mRNA(0.78±0.13,0.91±0.15 vs 1.53±0.23)in the infected and non-infected groups were significantly decreased(t=10.939～19.062),while the levels of H3K27me39(0.23%±0.05%,0.15%±0.03%vs 0.10%±0.02%),EZH2 mRNA(1.96±0.26,1.85±0.25 vs 1.15±0.29)and KDM5B(1.46±0.15,1.35±0.18 vs 0.94±0.12)were significantly increased(t=6.077～14.974),and the levels in the infected group were lower/higher than those in the non-infected group(t=2.017～10.688),with statistically significant differences(all P<0.05).There was a significant negatively correlation between H3K4me3 and H3K27me3 levels in placenta tissue of PROM(r=-0.604,P<0.05).The levels of H3K4me3,MLL1 and JMJD3 were negatively correlated with the histological stages of HCA(r=-0.646,-0.489,-0.503,all P<0.05).The levels of H3K27me3,EZH2 and KDM5B were positively correlated with the histological stages of HCA(r=0.632,0.515,0.520,all P<0.05).The cutoffvalues of H3K4me3 and H3K27me3 were 0.10%and 0.19%,respectively.The AUC(95%CI)value of the combined prediction of PROM combined with HCA infection was 0.896(0.882～0.947),and the sensitivity and specificity were 92.14%and 86.23%respectively,which was significantly higher than the diagnosis of a single index.Conclusion The levels of H3K4me3,H3K27me3 and modifying enzymes in the placenta tissue of PROM are closely related to HCA infection and histological stage,which has high clinical prediction value for HCA infection and is expected to be a new biomarker for clinical diagnosis.

Objective To study the expression levels and clinical significance of histone H3 trimethylation at lysine 4(H3K4me3),histone H3 trimethylation at lysine 27(H3K27me3)and modifying enzyme in placental tissue of patients with premature rupture of membranes(PROM)with chorioamnionitis.Methods Clinical data of 95 pregnant women treated in the Xi'an Gaoxin Hospital due to PROM from June 2021 to December 2023 were retrospectively collected,and they were divided into infected group and a non-infected group according to whether they were complicated with histological chorioamnionitis(HCA).Another 30 normal pregnant women were selected as the control group.Placental tissues of all subjects were collected and H3K4me3 and H3K27me3 levels were detected,and the expression levels of H3K4me3,H3K27me3 specific methyltransferase[mixed lineage leukemia protein-1(MLL1),Zeste enhancer homolog 2(EZH2)]and demethyltransferase[lysine-specific demethylase 5B(KDM5B),Jumonji domain-containing protein 3(JMJD3)]were detected by quantitative real-time PCR(qRT-PCR).The expression differences of H3K4me3,H3K27me3 and specific modifiers among the three groups and the correlation with the histological stage of HCA were analyzed.The Receiver operating characteristic curve(ROC)was plotted,the Area under curve(AUC)value was calculated,and H3K4me3 was evaluated.Predictive value of H3K27me3 for concurrent HCA infection.Result Compared with the control group,the levels of H3K4me3(0.08%±0.02%,0.12%±0.03%vs 0.25%±0.06%),MLL1 mRNA(1.32±0.16,1.44±0.23 vs 2.02±0.31),and JMJD3 mRNA(0.78±0.13,0.91±0.15 vs 1.53±0.23)in the infected and non-infected groups were significantly decreased(t=10.939～19.062),while the levels of H3K27me39(0.23%±0.05%,0.15%±0.03%vs 0.10%±0.02%),EZH2 mRNA(1.96±0.26,1.85±0.25 vs 1.15±0.29)and KDM5B(1.46±0.15,1.35±0.18 vs 0.94±0.12)were significantly increased(t=6.077～14.974),and the levels in the infected group were lower/higher than those in the non-infected group(t=2.017～10.688),with statistically significant differences(all P<0.05).There was a significant negatively correlation between H3K4me3 and H3K27me3 levels in placenta tissue of PROM(r=-0.604,P<0.05).The levels of H3K4me3,MLL1 and JMJD3 were negatively correlated with the histological stages of HCA(r=-0.646,-0.489,-0.503,all P<0.05).The levels of H3K27me3,EZH2 and KDM5B were positively correlated with the histological stages of HCA(r=0.632,0.515,0.520,all P<0.05).The cutoffvalues of H3K4me3 and H3K27me3 were 0.10%and 0.19%,respectively.The AUC(95%CI)value of the combined prediction of PROM combined with HCA infection was 0.896(0.882～0.947),and the sensitivity and specificity were 92.14%and 86.23%respectively,which was significantly higher than the diagnosis of a single index.Conclusion The levels of H3K4me3,H3K27me3 and modifying enzymes in the placenta tissue of PROM are closely related to HCA infection and histological stage,which has high clinical prediction value for HCA infection and is expected to be a new biomarker for clinical diagnosis.

Post-stroke depression,a common complication after stroke,severely affects the physical and mental rehabilitation of patients.Currently,the treatment of depression after stroke has limitations,such as limited efficacy and numerous adverse reactions.Preventing and treating depression after stroke have specific effects;however,the optimal intervention timing and duration remain unclear.Based on the principle of preventive treatment of diseases and the theory that"excessive fire consumes qi"(Huangdi Neijing),this article explores the influence of the stroke etiology and pathogenesis on secondary depression.The article proposes the pathogenesis of post-stroke depression as"wind and fire interacting-excessive fire consuming qi-spirit decline and qi depression,"where fire is the pathological cause,qi is the fundamental pathogenesis,and spirit is the disease manifestation.The disease can be prevented after the occurrence of stroke,but treatment should occur before"excessive fire consumes qi."Clearing fire,preserving the body's normal functions,and reducing fire to protect qi and prevent depression are advisable.After"excessive fire consumes qi,"which results in spirit decline and qi depression,dispersing stagnated liver qi for relieving qi stagnation,nourishing the spirit,and relieving depression to treat it are recommended.This article elaborates on the pathogenesis of post-stroke depression as"fire-qi-spirit,"based on the theory of"excessive fire consumes qi"and"preventing disease from exacerbating."This study proposes reducing fire to protect qi and nourishing the spirit to relieve depression to prevent and treat post-stroke depression,with the aim of providing a novel theoretical basis and practical guidance for preventing and treating post-stroke depression in traditional Chinese medicine.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.