ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration （IDD） in rats. MethodsIn the cell experiment， male rats were administrated with normal saline or low-， medium-， and high-dose （3.38， 6.75，13.5 g·kg^-1， respectively） Shentong Zhuyutang by gavage， respectively， and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin （IL）-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 （Fer-1）， respectively， to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum， this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385， respectively， in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 （CCK-8） assay and EdU staining were employed to measure the cell viability and proliferation， respectively. The Fe²⁺， glutathione （GSH）， and malondiadehyde （MDA） levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family 4 （ACSL4）， Collagen Ⅱ， Aggrecan， SIRT1， and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment， male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation， model， Shentong Zhuyutang-containing serum （13.5 g·kg^-1）， and positive control （nimesulide dispersible tablets， 0.18 mg·kg^-1） groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg^-1， and those in the sham operation and model groups were administrated with equal volumes of normal saline， once daily for 28 consecutive days. At the end of the last administration， the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group， the IL-1β group of nucleus pulposus cells showed elevated levels of Fe²⁺， MDA， and ACSL4 （P<0.05）， decreased cell viability， lowered GSH level， and down-regulated protein levels of GPX4， Collagen Ⅱ， and Aggrecan （P<0.05）. Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells （P<0.05）. Compared with the control group， the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the IL-1β group， the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group， the ML385 group showed down-regulated protein levels of Nrf2 and GPX4， lowered GSH level， and elevated Fe²⁺ and MDA levels （P<0.05）. In addition， the Ex 527 group showed down-regulated protein levels of SIRT1， Nrf2， and GPX4 （P<0.05）. The results of the animal experiment showed that compared with the sham operation group， the model group had severe degeneration of the intervertebral disc tissue with increased pathological score， up-regulated protein level of ACSL4 （P<0.05）， and down-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. Compared with the model group， the Shentong Zhuyutang group showed alleviated IDD with declined pathological score， down-regulated protein level of ACSL4 （P<0.05）， and up-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells， thereby delaying the process of IDD in rats.

[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.

OBJECTIVE To establish the ultra-high performance liquid chromatography （UPLC） fingerprint of Jingtian granule， and to evaluate its quality by chemical pattern recognition. METHODS Luna® Omega Polar C18 column （150 mm×2.1 mm， 1.6 μm） was used as the chromatographic column， and acetonitrile-0.2% phosphoric acid solution was used as the mobile phase for gradient elution. The flow rate was 0.2 mL/min， the column temperature was 30 ℃， and the detection wavelength was 265 nm. With peak 16 as the reference peak， the UPLC fingerprint of Jingtian granule was established by the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. The common peaks were identified， the similarity evaluation was carried out， and the ownership of each common peak was confirmed. Hierarchical cluster analysis （HCA） and principal component analysis （PCA） in chemical pattern recognition methods were used to classify 13 batches of samples （S1- S13）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） was used to identify the key components of the differences between different batches of samples. RESULTS RSDs of precision， repeatability and stability of the UPLC method were not more than 4.4%. A total of 25 common peaks were identified in the fingerprints of 13 batches of Jingtian granules. By comparing with the reference substance fingerprint， 10 common peaks were identified， namely peak 3 （hydroxymethyl-2-furaldehyde）， peak 5 （salidroside）， peak 8（chlorogenic acid）， peak 15 （cinnamic acid）， peak 19 （aloe-emodin）， peak 20 （ammonium glycyrrhizinate）， peak 21 （rhein）， peak 23 （emodin）， peak 24 （glycyrrhetinic acid）， peak 25 （chrysophanol）. The similarities of fingerprints of 13 batches of samples were 0.955-0.996. The results of HCA showed that 13 batches of samples could be divided into three categories， among which samples S1， S5， S7， S11-S13 were clustered in one category， S4 and S6 were clustered in one category， S2， S3 and S8-S10 were clustered in one category. PCA results showed that the cumulative variance contribution rate of principal components 1-7 was 92.666%. OPLS-DA further identified 13 differential components， which were mainly derived from Polygonati Rhizoma with wine steaming， Rhodiolae Crenulatae Radix Et Rhizoma， prepared Rhei Radix Et Rhizoma and Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle. CONCLUSIONS The established UPLC fingerprint of Jingtian granule is simple， stable and reproducible. Combined with the chemical pattern recognition method， it can effectively reveal the overall quality difference between different batches of Jingtian granule. The quality of Polygonati Rhizoma with wine steaming， Rhodiolae Crenulatae Radix Et Rhizoma， prepared Rhei Radix Et Rhizoma， Dioscoreae Nipponicae Rhizoma， Polyporus， Cinnamomi Ramulus， Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle is the key to the overall quality of Jingtian granule.

Objective: To investigate the incidence and trends of liver, lung, breast, colorectal and gastric cancers in Nanning City from 2018 to 2022. Methods: Data of new cases of liver, lung, breast, colorectal and gastric cancers in Nanning City from 2018 to 2022 were collected through the big data platform of the Nanning Health Propaganda and Information Center's Hospitalization System. The incidence rates were calculated and standardized using the data of the seventh national population census in 2020. The age, gender, and urban-rural distribution of the five malignant tumor cases were descriptively analyzed. The trends in incidence of the five malignant tumors were analyzed using annual percent change (APC). Results: From 2018 to 2022, the crude and standardized incidence rates of liver cancer in Nanning City were 24.46/105 and 26.39/105, respectively, showing upward trends (APC=15.122% and 13.111%, both P<0.05). The crude and standardized incidence rates of lung cancer were 23.42/105 and 25.83/105, respectively, showing upward trends (APC=13.714% and 10.056%, both P<0.05). The crude and standardized incidence rates of breast cancer were 19.13/105 and 20.29/105, respectively, with no significant trends (APC=-5.129% and -5.164%, both P>0.05). The crude incidence rate of colorectal cancer was 18.81/105, showing an upward trend (APC=8.164%, P<0.05), while the standardized incidence rate was 20.64/105, with no significant trend (APC=5.044%, P>0.05). The crude incidence rate of gastric cancer was 7.27/105, showing an upward trend (APC=5.984%, P<0.05), while the standardized incidence rate was 7.98/105, with no significant trend (APC=3.304%, P>0.05). The age of onset peak for liver cancer was 65 to <70 years, for lung cancer was 75 to <80 years, for breast cancer was 55 to <60 years, for colorectal cancer was 80 to <85 years, and for gastric cancer was 75 to <80 years. The standardized incidence rates of liver, lung, colorectal and gastric cancers were higher in males than in females (all P<0.05). The standardized incidence rates of liver, lung and gastric cancers were higher in rural areas than in urban areas, while the standardized incidence rates of breast and colorectal cancers were lower in rural areas (all P<0.05). Conclusions The incidence rates of liver, lung, colorectal and gastric cancers in Nanning City showed upward trends from 2018 to 2022, while the incidence rate of breast cancer remained stable. The standardized incidence rates of liver, lung, colorectal and gastric cancers were higher in males, and the standardized incidences of liver, lung and gastric cancers were higher in rural areas.

Objective: To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome. Methods: One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website. Results: There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways. Conclusion Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.

Objective: To analyze the trajectories of blood pressure and body mass index (BMI) among primary and secondary school students aged 7-17 in Shunyi District of Beijing, and to explore the association between different growth trajectories and visual outcomes, so as to provide a scientific basis for the prevention and control of common diseases in children and adolescents. Methods: Health examination data (including vision, blood pressure and BMI) of primary and secondary school students in Shunyi District of Beijing from 2019 to 2023 were collected and analyzed. Group based trajectory modeling was used to classify the trajectories of BMI and blood pressure (systolic and diastolic) into distinct groups among students aged 7-17 years. The relationship between these trajectories and visual outcomes was examined using binary Logistic regression analysis. Results: The prevalence of screening myopia among students in Shunyi District was 57.2%, while the rate of moderate to severe visual impairment was 55.8%. Based on the latent growth model, the trajectories of systolic blood pressure, diastolic blood pressure, and BMI were divided into three groups:low growth trajectory, moderate growth trajectory and high maintenance trajectory. Logistic regression analysis revealed that, compared to the low growth trajectory group, the moderate growth and high maintenance trajectory groups for systolic blood pressure, diastolic blood pressure, and BMI were associated with an increased risk of screening myopia ( OR =1.14, 1.11; 1.07, 1.19 ; 1.06, 1.08, P <0.05). Similarly, the moderate growth and high maintenance trajectory groups for systolic blood pressure, diastolic blood pressure, and BMI were similarly associated with an increased risk of moderate to severe visual impairment ( OR = 1.12 , 1.12; 1.09, 1.17; 1.08, 1.11, P <0.05). Conclusions Moderate growth and high maintenance trajectories of blood pressure and BMI are associated with an increased risk of screening myopia and moderate to severe visual impairment among students. It is recommended to closely monitor changes in blood pressure and overweight/obesity trajectories in primary and secondary school students, conduct regular assessments, and actively prevent the development and progression of multimorbidity and comorbidity.

OBJECTIVE To summarize the effective measures and implementation effects of Australia in improving drug accessibility， and provide reference for the optimization and promotion of drug accessibility policies in China. METHODS By searching the official website of the Australian Federal Government and relevant literature， this study introduced Australia’s practical experiences in the Pharmaceutical Benefits Scheme （PBS）， drug registration and PBS access， drug pricing and procurement policies， generic drug price competition and disclosure， and orphan drug registration and approval policies. It summarized the effective measures taken by the federal government to improve drug accessibility and control drug expenditure. RESULTS & CONCLUSIONS The good management collaboration mechanism， flexible drug price negotiation system， and comprehensive drug accessibility policy support system of the Australian health system have maintained a good balance between drug accessibility， patient burden， and government subsidies in the long run， effectively ensuring the accessibility of Australian drugs. It is recommended that our country strengthen policy coordination and departmental cooperation in terms of drug accessibility， optimize the registration and accelerated approval process for new drugs， improve the price management and negotiation mechanism， and establish a comprehensive drug accessibility support system.

ObjectiveTo understand the infection characteristics of multidrug-resistant organisms (MDROs) in hospitalized patients in a tertiary sentinel hospital in Shanghai, so as to provide an evidence for the development of targeted prevention and control measures. MethodsData of MDROs strains and corresponding medical records of some hospitalized patients in a hospital in Shanghai from 2021 to 2023 were collected, together with an analysis of the basic information, clinical treatment, underlying diseases and sources of sample collection. ResultsA total of 134 strains of MDROs isolated from hospitalized patients in this hospital were collected from 2021 to 2023 , including 63 strains of methicillin-resistant Staphylococcus aureus (MRSA), 57 strains of carbapenem-resistant Acinetobacter baumannii (CRAB), and 14 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP). Of the 134 strains, 30 strains were found in 2021, 47 strains in 2022 and 57 strains in 2023. The male-to-female ratio of patients was 2.05∶1, with the highest percentage (70.90%) in the age group of 60‒<90 years. The primary diagnosis was mainly respiratory disease, with lung and respiratory tract as the cheif infection sites. There was no statistically significant difference in the distribution of strains between different genders and infection sites (P>0.05). However, the differences in the distribution of strains between different ages and primary diagnosis were statistically significant (P<0.05). Patients who were admitted to the intensive care unit (ICU), had urinary tract intubation, were not artery or vein intubated, were not on a ventilator, were not using immunosuppresants or hormones, and were not applying radiotherapy or chemotherapy were in the majority. There was no statistically significant difference in the distribution of strains for whether received radiotherapy or chemotherapy or not (P>0.05), while the differences in the distribution of strains with ICU admission history, urinary tract intubation, artery or vein intubation, ventilator use, and immunosuppresants or hormones use or not were statistically significant (all P<0.05). The type of specimen was mainly sputum, the hospitalized ward was mainly comprehensive ICU, the sampling time was mainly in the first quarter throughout the year, the number of underlying diseases was mainly between 1 to 2 kinds, the application of antibiotics ≥4 kinds, and those who didn’t receive any surgery recently accounted for the most. There were statistically significant differences in the distribution of strains between different specimen types, wards occupied and history of ICU stay (P<0.05), but no statistically significant difference in the distribution of strains between different sampling times, number of underlying diseases and types of antibiotics applied (P>0.05). ConclusionThe situation of prevention and control on MDROs in this hospital is still serious. Focus should be placed on high-risk factors’ and infection monitoring and preventive measures should be strengthened to reduce the incidence rate of MDROs infection.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Objective: To investigate the nutritional status and influencing factors among Tibetan and Mongolian children and adolescents aged 7-18 years in high-altitude regions, so as to provide evidence for early prevention and control of malnutrition in this population. Methods: From May to June 2022, a cluster sampling method was employed to recruit 1 019 Tibetan and Mongolian children and adolescents aged 7-18 years from two primary and secondary schools in Golmud City. Physical examinations, dietary frequency questionnaires, and physical activity assessments were conducted. Nutritional status was classified as obesity, combined overweight/obesity, underweight, or central obesity according to national standards including Screening for Overweight and Obesity among School-age Children and Adolescents, Screening Standard for Malnutrition of School-age Children and Adolescents, Blue Book on Obesity Prevention and Control in China. Chi-square tests, t-test and Logistic regression analyses were performed to identify factors associated with different nutritional statuses. Results: The detection rates of obesity, combined overweight/obesity, underweight, and central obesity were 8.0%, 18.1%, 5.2%, and 19.7%, respectively. The height of children and adolescents across all age groups was generally lower than the national standard values. Tibetan participants exhibited significantly lower height-for-age Z-scores (HAZ)(9-10, 13-17 years, Z =2.01, 2.78, 4.16, 3.38, 4.12, 3.63, 3.00) and BMI-for-age Z-scores (BAZ) compared to Mongolian participants ( Z =-2.95, -2.47, -2.31, -2.89, -2.14, -2.17)( P < 0.05 ). Multivariate Logistic regression revealed that Mongolian children and adolescents had higher risks of obesity ( OR =2.20) and combined overweight/obesity ( OR = 2.18 ) ( P <0.05). Additionally, insufficient moderate-to-vigorous physical activity (MVPA) was associated with an increased risk of central obesity ( OR =1.48, P <0.05), compared with children and adolescents who meet the standard of MVPA. Conclusions The rates of overweight and obesity among Tibetan and Mongolian children and adolescents in Golmud City are higher, influenced by multiple factors. Nutrition interventions and physical activity strategies tailored to ethnic characteristics should be implemented, with emphasis on promoting MVPA to improve nutritional outcomes in this population.