Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

Pancreatic cancer is characterized by significant drug resistance,and despite continuous advancements in treatment regimens,the 5-year survival rate of patients remains low.The nuclear factor-κB(NF-κB)signaling pathway,frequently mutated in tumors,has been identified as a critical factor in triggering drug resistance.Multiple studies have demonstrated that strategies targeting NF-κB signaling transduction exhibit promising outcomes in pancreatic cancer treatment.Therefore,exploring the relationship between the NF-κB signaling pathway and drug resistance in pancreatic cancer has become a research hotspot in pancreatic cancer treatment.This review summarizes recent advances in the relationship between NF-κB signaling pathway and tumor drug resistance,as well as its role in pancreatic cancer treatment.Specifically,the mechanisms by which the NF-κB signaling pathway mediates drug resistance in pancreatic cancer are elaborated from two perspectives:chemotherapy and immunotherapy,aiming to provide insights for pancreatic cancer treatment and future research.

Objective To investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2(UBAC2)mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.Methods The GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues,as well as its expression in colorectal cancer tissues at different stages.The correlation between Wilms tumor 1-associated protein(WTAP)and UBAC2 expression was analyzed.The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients.The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines.For UBAC2 knockdown experiments,SW480 cells were divided into control group(no treatment),sh-NC group(transfected with sh-NC negative control plasmid),and sh-UBAC2 group(transfected with sh-UBAC2 plasmid).For WTAP knockdown experiments,groups included control group(no treatment),si-NC group(transfected with negative control siRNA),and si-WTAP group(transfected with WTAP-targeting siRNA).For UBAC2 overexpression experiments,groups were control group(no treatment),si-WTAP group(transfected with pcDNA3.1 empty plasmid),and si-WTAP+OE-UBAC2 group(transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2).Western blotting was used to detect the protein expression levels of UBAC2,WTAP,E-cadherin,N-cadherin,and Vimentin;qRT-PCR was applied to detect the expression level of UBAC2 mRNA;Transwell assays were conducted to assess cell invasion and migration abilities.MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA;RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA.In nude mouse colorectal cancer lung metastasis experiments,groups included LV-sh-NC group(tail vein injection of SW480 cells stably infected with LV-sh-NC)and LV-sh-UBAC2 group(tail vein injection of SW480 cells stably infected with LV-sh-UBAC2).After 42 d of tumor-implantation in nude mice,lung tissues were harvested:the number of lung nodules observed by hematoxylin/eosin(HE)staining,and the expression level of Luc2 mRNA detected by qRT-PCR.Results GEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues,and it gradually increased with the progression of tumor stage(P<0.05).The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells(P<0.05).Compared with sh-NC group,sh-UBAC2 group showed significantly increased E-cadherin protein expression,significantly decreased N-cadherin and Vimentin protein expression,and significantly reduced number of invaded and migrated SW480 cells(P<0.05).GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression(r=0.24,P<0.001).Compared with si-NC group,si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells(P<0.05).MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group(P<0.05).RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA.Compared with control group,si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05);compared with si-WTAP group,si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05).The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group,and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group(P<0.05).Conclusion UBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition(EMT)process in colorectal cancer cells,thereby affecting the invasion and migration abilities of colorectal cancer cells.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

The core of theory of visceral manifestation of spleen is about'spleen in charge of transportation and transformation,spleen qi dispersing the essence'.Middle-jiao spleen-earth has the functions of digesting food and transporting food essence,and maintaining the homeostasis of glucose and lipid metabolism in the body.'Spleen in charge of transportation and transformation,spleen qi dispersing the essence'functions like the glucose and lipid metabolism at physiological state.The deficiency of spleen results in the dysfunction of food in-take and digestion and the susceptibility to external pathogens;qi deficiency and blood stasis lead to the interior damp-heat,and the long-term accumulation of damp-heat develops into stasis and then turns into toxins,which eventually induces inflammation-to-tumor transition.The pathogenesis of'spleen deficiency being the root cause and stasis blended with toxins'is correlated with the pathological changes of inflammation-to-tumor transition.The therapy of strengthening the spleen,dispersing essence and removing turbidity is effective on improving the disorder of glucose and lipid metabolism,and the therapy of strengthening the spleen,resolving stasis and removing toxin is effective on restraining the process of inflammation-to-tumor transition in the stomach.It has become a new direction in the field of spleen-stomach research to expound the scientific connotation of the essence of spleen function of'spleen in charge of transportation and transformation,spleen qi dispersing the essence'from the perspective of glucose and lipid metabolism,to focus on the inflammation-to-tumor transition process of major diseases of digestive system,to explore the evolution of the traditional Chinese medicine syndromes of inflammatory diseases and precancerous lesions of the digestive tract,and to reveal the pharmacological mechanism of treatment from the perspective of spleen,which will enrich the scientific connotation of theory of visceral manifestation of spleen and promote the modernization and internationalization of traditional Chinese medicine.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.