ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid （23-HBA）， a key constituent of Pulsatillae Radix， on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-（methylnitrosamino）-1-（3-pyridyl）-1-butanone （NNK） and lipopolysaccharide （LPS） in mice， alongside exploring its influence on immune cells and delving into the underlying mechanisms. MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control， model， aspirin （10 mg·kg^-1）， and low-， medium-， and high-dose （3.75， 7.5， 15 mg·kg^-1， respectively） 23-HBA groups. The treatment lasted for 26 weeks， after which the spleen， lung， and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 （TTF-1）， neuron-specific enolase （NSE）， and proliferating cell nuclear antigen （Ki-67） in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages， myeloid-derived suppressor cells （MDSCs）， and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 （JAK2）， Src homology 2 domain-containing phosphatase 2 （SHP2）， and suppressor of cytokine signaling 3 （SOCS3）. Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 （p-STAT3）， p53， and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA. ResultsCompared with the normal group， the lung and spleen indexes of the model group were increased to varying degrees （P<0.05， P<0.01）， the expression of TTF-1， NSE and Ki-67 protein was significantly increased （P<0.05， P<0.01）， and the serum levels of TNF-α， IL-1β and IL-6 were significantly increased （P<0.01）. The number of macrophages in the model group was significantly decreased （P<0.01）， and the number of exhausted T cells and MDSCs was significantly increased （P<0.05， P<0.01）. Compared with the model group， the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly （P<0.05）， and the lung index of mice in the middle dose group of 23-HBA decreased significantly （P<0.05）. The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group （P<0.05， P<0.01）. The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group （P<0.05， P<0.01）. The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased （P<0.05）， and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased （P<0.05， P<0.01）. The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased （P<0.05）， and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased （P<0.05， P<0.01）. In addition， 23-HBA had strong molecular docking ability to SHP2， SOCS3 and JAK2 （≥7 kcal·mol^-1）， and significantly down-regulated the protein levels of p-STAT3， SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma （P<0.01）. Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses， improving the tumor immune microenvironment， and regulating key signaling pathways.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

OBJECTIVE: To compare the short-term effectiveness between Gamma 3 intramedullary nails and Gamma 3 U-Blade system in the treatment of osteoporotic intertrochanteric fractures in the elderly. METHODS: A retrospective analysis was conducted on the clinical data of 124 elderly patients with osteoporotic intertrochanteric fractures, who were admitted between February 2020 and February 2023 and met the selection criteria. The fractures were fixed with Gamma 3 intramedullary nails in 65 patients (control group) and Gamma 3 U-Blade systems in 59 patients (UB group). The differences between the two groups were not significant in age, gender, body mass index, American Society of Anesthesiologists (ASA) classification, bone mineral density, time from injury to operation, fracture classification, and affected side ( P>0.05). The operation time, intraoperative blood loss, hospital stay, and fracture healing time were recorded; the tip-apex distance, fracture reduction quality, and lag screw position were evaluated on X-ray films at immediate after operation; the lag screw sliding distance and change value of neck-shaft angle were measured on X-ray films at last follow-up. Harris hip score at 1 year after operation and the occurrence of internal fixation-related complications were compared between the two groups. RESULTS: The operation time, intraoperative blood loss, and hospital stay in the UB group increased compared to the control group, but the differences were not significant ( P>0.05). All patients in both groups were followed up 12-24 months (mean, 17.1 months). At 12 months after operation, there was no significant difference in the Harris hip score between the two groups ( P<0.05). Radiological examination showed that there was no significant difference between the two groups ( P>0.05) in terms of tip-apex distance, fracture reduction quality, and lag screw position. Fractures healed in both groups, and there was no significant difference in healing time ( P>0.05). At last follow-up, the change value of neck-shaft angle and lag screw sliding distance in the UB group were significantly lower than those in the control group ( P<0.05). During follow-up, no related complications occurred in the UB group, while 6 cases (9.2%) in the control group experienced complications, and the difference in the incidence was significant ( P<0.05). CONCLUSION For the osteoporotic intertrochanteric fractures in the elderly, the Gamma 3 U-Blade system fixation can achieve good short-term effectiveness, with better imaging results compared to Gamma 3 intramedullary nails fixation.
Humans ; Retrospective Studies ; Hip Fractures/surgery* ; Male ; Female ; Aged ; Fracture Fixation, Intramedullary/methods* ; Osteoporotic Fractures/surgery* ; Bone Nails ; Bone Screws ; Aged, 80 and over ; Treatment Outcome ; Fracture Healing ; Operative Time ; Length of Stay

OBJECTIVE: To analyze the disease burden of pelvic fractures at the global, regional, and national levels from 1990 to 2023 using data from the 2023 Global Burden of Disease Study (GBD), and to predict the disease burden through 2050. METHODS: Leveraging data from the GBD 2023, this study investigated the disease burden of pelvic fractures across 204 countries and regions. Assessment indicators included incidence rate, prevalence rate, and years lived with disability (YLDs). The Joinpoint regression model was employed to analyze trends in pelvic fracture burden from 1990 to 2023, while the average annual percentage change (AAPC) was used to quantify this temporal trend. The relationship between the socio-demographic index and pelvic fracture burden was evaluated. Furthermore, the long short-term memory (LSTM) model was applied to predict trends in pelvic fracture burden through 2050. RESULTS: In 2023, the estimated number of new pelvic fracture cases globally was 7 479 884 [95% uncertainty interval ( UI): 5 293 401-10 611 876], representing a 42.74% increase from 1990. In the same year, the number of prevalent pelvic fracture cases and YLDs were 23 007 508 (95% UI: 21 021 518-25 327 165) and 3 909 228 person-years (95% UI: 2 725 498-5 194 385), respectively. Additionally, age-standardized rates exhibited an opposing downward trend. Significant disparities in the disease burden of pelvic fractures were identified across different age groups, genders, and social contexts. According to predictions from the LSTM model, the global age-standardized incidence rate (ASIR) of pelvic fractures will be approximately 88.44 per 100 000 persons by 2050, while the total number of incident cases will rise to 8 547 095. CONCLUSION Although the overall incidence rate, prevalence rate, and YLDs of pelvic fractures have exhibited an upward trend over the past three decades, the ASIR, age-standardized prevalence rate (ASPR), and age-standardized years of life lost rate (ASYR) have shown a downward trend. It is predicted that over the upcoming 26-year period, the age-standardized rate of disease burden due to pelvic fractures will further decrease, while the number of incident cases and prevalent cases will continue to exhibit an upward trend. Formulating more targeted disease prevention strategies is critical to addressing disparities across genders, regions, and other dimensions, and to mitigating the burden of pelvic fractures.
Humans ; Fractures, Bone/epidemiology* ; Pelvic Bones/injuries* ; Male ; Female ; Middle Aged ; Adult ; Incidence ; Prevalence ; Aged ; Global Burden of Disease/trends* ; Global Health ; Adolescent ; Cost of Illness ; Young Adult ; Forecasting ; Disability-Adjusted Life Years ; Memory, Short-Term

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Glioma is the most common primary malignant tumor of the central nervous system in adults. Despite the standard treatment of surgery combined with radiotherapy and chemotherapy, the prognosis for high-grade glioma patients remains poor, highlighting the urgent need to further explore its pathogenesis and develop new therapeutic strategies. This article reviews the research progress in the field of glioma in China in 2024, covering tumorigenesis mechanisms, tumor immune microenvironment composition, advances in imaging techniques and novel imaging agents, improvements in surgical approaches, mechanisms of radio- and chemoresistance, and explorations of new therapeutic modalities. These studies provide a solid theoretical foundation for advancing clinical diagnosis and treatment of gliomas and may offer new opportunities to improve patient outcomes.

Objective This study aimed to explore the prescription regularity of Mercury(Zuotai)detoxification formula in Tibetan classic medical literatures based on data mining.Methods Mercury(Zuotai)detoxification formula of were collected from 22 ancient Tibetan medical literatures including the Four Medical Tantras,Medicine of Moon King,One Hundred Thousand Fists and Eight Essential Collections of Medicine,et al.The database of drugs,medicinal properties,five-source,six-flavor,and three-chemical flavor was established.R 4.2.2,IBM SPSS Modeler 18.0,Origion 2024 and other software were used to conduct frequency statistical analysis,Apriori association rule analysis and cluster analysis of the category,property and flavor,and five-source of Mercury(Zuotai)detoxification compound drugs,and interpret the statistical results in combination with the theory of Tibetan medicine.Results A total of 52 formulas were collected,containing 213 Tibetan medicines,with a cumulative frequency of 1066 times.The medicines involved in the prescription are mainly plant-based,and most of them are"cold"drugs;the medicinal flavor of drugs is mainly bitter,sweet,and pungent,with the five sources of emptiness,wind and water predominating;the most frequently occurring medicine was Mercury(Zuotai),followed by Terminalia Chebula,Musk,Geranium,Saffron,and Nutmeg.High-frequency medicines such as Mercury(Zuotai),Musk,Strychni Semen,Aconitum Tanguticum,Pedicularis Trichoglossa,Swertia Verticillifolia,and Sinapis Alba have detoxification effects.Musk also has the effect of aromatherapy,Terminalia Chebula can reconcile the nature of the medicine and the three causes of the disease effectively.The"six good medicines",including Geranium,Saffron,Nutmeg,White cardamom,Cloves,and Tsaoko Amomum Fruit,can harmonize qi and blood,and treat diseases of internal organs of the body.The analysis of association rules showed 24 pairs of medicines combinations with a support degree exceeding 59.62,and 9 groups of three-drug combinations,predominantly involving Mercury(Zuotai),Terminalia Chebula,Musk,and"six good medicines".The cluster analysis of medicines with a frequency of>10 produced 7 clustered formulas,primarily characterized by their efficacy in clearing away heat and toxins,as well as regulating the five internal organs and six viscera.Conclusion Most medicines in the Mercury(Zuotai)detoxification formula are primarily composed of botanicals,cold and bitter drugs,which is consistent with the heat-clearing and detoxifying therapy in Tibetan medicine.The medication pattern of the Mercury(Zuotai)detoxification formula is characterized by the use of Terminalia Chebula to reconcile the medicinal properties,detoxifying medicines to detoxify,aromatic drugs to rapidly eliminate or expel toxins,and six good medicines to protect the viscera.The combined use of these medicines plays a role in clearing away heat and toxins,opening up the orifices and collaterals,and harmonizing the functions of the viscera.The study provides data to support the medication rules of the Tibetan medicine Mercury(Zuotai)detoxification prescription.

Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.