OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules， the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization （WHO） guideline-making norms and the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions （19 items were screened by the nominal group technique）， retrieving evidence （from Chinese and English databases and grey literature）， assessing safety （integrating drug monitoring data and clinical investigations）， and forming recommendations and consensus suggestions （3 recommendations were reached via the GRADE grid method， and 16 consensus suggestions were reached by the majority vote rule）. The results indicate that the consensus clearly states that this medicine （Dieda Huoxue capsules） is applicable to conditions like traumatic injury， blood stasis-induced pain， and sudden lumbar sprains. The recommended dose is 6 capsules each time， twice a day. Combining oral administration with external application can enhance the efficacy， and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis， the Delphi method， and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration， conflict-of-interest statements， and evidence evaluation through 12 appendices， providing methodological support for the clinical translation of the consensus. In the future， it will be continuously improved through a dynamic revision mechanism.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

Objective To analyze the disease burden,changing trends,and differences of atrial fibrillation(AF)/atrial flutter(AFL)globally and in China and Japan from 1990 to 2021,and to predict their future trends,aiming to provide references for health decision-making.Methods Based on the Global Burden of Disease Study Database 2021(GBD 2021),we extracted age-standardized prevalence rate(ASPR)and age-standardized disability-adjusted life year rate(ASDALYR)data for AF/AFL by sex globally,in China,and Japan.The estimated annual percentage change(EAPC)was used to assess the trends.Joinpoint regression analysis and the Bayesian age-period-cohort(BAPC)model were employed for trend analysis and prediction.Results From 1990 to 2021,the ASPR and ASDALYR for AF/AFL in males were increased significantly globally,with EAPC of 0.05(95%CI:0.01～0.08)and 0.09(95%CI:0.08～0.11),respectively.Changes were significantly declined in females,with EAPC of-0.11(95%CI:-0.14～-0.07)and-0.10(95%CI:-0.12～-0.07).In China,the ASPR for AF/AFL were increased in both males and females,with those of males more notably(EAPC=0.77,95%CI:0.65～0.88).However,the ASDALYR for AF/AFL showed gender divergence,with an increase in males(EAPC=0.40,95%CI:0.30～0.49)while a decrease in females(EAPC=-0.55,95%CI:-0.67～-0.44).In Japan,both the ASPR and ASDALYR for males and females showed continuous declines,and the reduction was more pronounced among females(ASPR EAPC=-1.77,95%CI:-2.32～-1.22;ASDALYR EAPC=-1.73,95%CI:-2.11～-1.35).Joinpoint regression analysis showed that from 1990 to 2021,for the ASDALYR of AF/AFL,the average annual percentage change(AAPC)was 0.28%(P<0.001)for Chinese males and-0.37%(P<0.001)for Chinese females,while the AAPC was-0.70%(P<0.001)and-1.43%(P<0.001)for Japanese males and females.BAPC model revealed that by 2036,the ASDALYR for Chinese males is predicted to increase from 91.45 per 100 000 in 2022 to 101.11 per 100 000,and for females is from 88.85 per 100 000 to 100.98 per 100 000.For Japanese males,the ASDALYR is projected to increase slightly from 88.79 to 89.86 per 100 000,while for females,it is projected decrease slightly from 41.13 to 39.67 per 100 000,indicating only minor fluctuations in the ASDALYR for both Japanese males and females.Conclusion The disease burden of AF/AFL continues to increase globally and in China.So,Japan's lifestyle and health policies are worth considering,and more scientific and effective public health policies and clinical intervention strategies should be formulated and implemented.Countermeasure The relevant government agencies should promote the transformation of the food industry through the policy-market mechanism,carry out activities related to national health management,and continuously optimize the AF/AFL management model of medical and health institutions to effectively cope with this disease burden change.

Objective Bioinformatics and machine learning were used to identify associations between key genes in obesity and osteoarthritis(OA)and immune infiltrating cells.Methods Three datasets GSE55235,GSE44000 and GSE151839 were screened from the gene expression omnibus(GEO)database,and differentially expressed genes(DEGs)were obtained by R software,and their potential biological functions were explored through gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment analysis.The minimum absolute contraction and selection operator(LASSO)regression algorithm combined with support vector machine(SVM)was used to screen characteristic genes,the diagnostic value of key genes was verified by receiver operating characteristic(ROC)curve,and the immune infiltration was assessed by CIBERSORT algorithm.The mRNA-miRNA regulatory network was constructed using NetworkAnalyst database to predict target miRNA and Cytoscape software,and the correlation between key genes and immune infiltration was analyzed.Results GO gene enrichment analysis obtained 99 DEGs.Cellular activation in the immune system and immune response is highly enriched.KEGG pathway analysis showed significant enrichment of interleukin(IL-17),nuclear factor-κB(NF-κB),B-cell receptor and chemokine signaling pathways.Two key diagnostic genes(MXRA5 and MYC)were identified based on machine learning.Immunoinfiltration analysis showed that MXRA5 was associated with resting and activated CD4 memory T cells,activated NK cells,resting and activated mast cells,and M0 macrophages.In addition,MYC is associated with resting and activated CD4 memory T cells,plasma cells,activated NK cells,resting and activated mast cells,M2 macrophages,and eosinophils.CD4+cells,NK cells and mast cells were significantly associated with these two pivot genes.Conclusion Two key immune-related genes were identified through bioinformatics analysis,which may provide new targets for the treatment of obesity-related OA.

Wu Liande’s spirit was formed during the development of modern public health in China. It is a unity of the spirit of patriotism, humanitarianism, scientific exploration, and dedication, and a valuable resource and vivid textbook for medical students to carry out professional spirit education. Promoting Wu Liande’s spirit in the new era is not only conducive to inspiring the patriotism of medical students, bravely undertaking the mission of the times, and devoting themselves to the cause of human health, but also conducive to guiding medical students to refine benevolence and skill, and fulfill the sacred oath of medical students. To cultivate the professional spirit of medical students with Wu Liande’s spirit, it is necessary to achieve the "integration of specialized courses and ideological and political education" , promote the collaborative development of ideological and political courses and curriculum ideological and political education, innovate teaching methods and use modern information technology to empower Wu Liande’s spirit to be visualized and expressed, and take discipline practice as the starting point to expand the new path of professional spirit practice education for medical students.

Objective To design and validate a novel surgical guide for retrieval of foreign body in jaw. Methods Firstly, a surgical guide based on cone beam computed tomography and trephine technique was designed to remove broken dental instrument fragments. Its feasibility and accuracy were assessed by removing broken dental instrument in goat mandible, and then it was successfully applied in clinical cases. The linear and angular discrepancies between actual and planned columnar bone with imaginary fragment was analyzed. The euclidean distance was measured at the hex and apex of the columnar bone and the angle of axis deviation was also calculated. We obtained seven parameters (cdh, cda, hdh, hda, vdh, vda, and ad) to describe deviations. Results Mean central deviation at the hex and apex was (0.51 ± 0.14) mm and (0.62 ± 0.19) mm, respectively. Accompanying mean values were as follow: horizontal deviation at the hex was (0.48 ± 0.16) mm, horizontal deviation at the apex was (0.52 ± 0.22) mm, vertical deviation at the hex was (0.17 ± 0.09) mm, vertical deviation at the apex was (0.29 ± 0.13) mm, and angular deviation of (5.38 ± 3.43) degrees. In a clinical case, the guide successfully located and removed the fracture file. Conclusion This study reveals that this kind novel surgical guide could aid to locate and remove the foreign body in jaw.

BACKGROUND: At the end of 2019, the outbreak of coronavirus disease 2019 (COVID-19) severely damaged and endangered people's lives. The public health emergency management system in China has played an essential role in handling the response to the outbreak, which has been appreciated by the World Health Organization and some countries. Hence, it is necessary to conduct an overall analysis of the development of the health emergency management system in China. This can provide a reference for scholars to aid in understanding the current situation and to reveal new research topics. METHODS: We collected 2247 international articles from the Web of Science database and 959 Chinese articles from the China National Knowledge Infrastructure database. Bibliometric and mapping knowledge domain analysis methods were used in this study for temporal distribution analysis, cooperation network analysis, and co-word network analysis. RESULTS: The first international article in this field was published in 1991, while the first Chinese article was published in 2005. The research institutions producing these studies mainly existed in universities and health organizations. Developed countries and European countries published the most articles overall, while eastern China published the most articles within China. There were 52 burst words for international articles published from 1999-2018 and 18 burst words for Chinese articles published from 2003-2018. International top-ranked articles according to the number of citations appeared in 2005, 2007, 2009, 2014, 2015, and 2016, while the corresponding Chinese articles appeared in 2003, 2004, 2009, and 2011. CONCLUSIONS There are differences in the regional and economic distribution of international and Chinese cooperation networks. International research is often related to timely issues mainly by focusing on emergency preparedness and monitoring of public health events, while China has focused on public health emergencies and their disposition. International research began on terrorism and bioterrorism, followed by disaster planning and emergency preparedness, epidemics, and infectious diseases. China considered severe acute respiratory syndrome as the starting research background and the legal system construction as the research starting point, which was followed by the mechanism, structure, system, and training abroad for public health emergency management.
Betacoronavirus ; China ; epidemiology ; Communicable Disease Control ; organization & administration ; Coronavirus Infections ; epidemiology ; prevention & control ; Disease Outbreaks ; prevention & control ; Humans ; Internationality ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; prevention & control