ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase （AMPK）/peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α） signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment （VCI） and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group， and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group， the high-dose group of Tongmai Kaiqiao pills （27.6 g·kg^-1）， the low-dose group of Tongmai Kaiqiao pills （13.8 g·kg^-1）， the combination group （27.6 g·kg^-1 Tongmai Kaiqiao pills + 25 mg·kg^-1 dorsomorphin）， and the donepezil hydrochloride group （0.45 g·kg^-1） according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs， the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin （HE） staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate （ATP） in the brain hippocampus was detected by colorimetry， and reactive oxygen species （ROS） level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR （Real-time PCR）. Pathological changes in mitochondria were observed by transmission electron microscopy （TEM）， and AMPK， PGC-1α， phosphorylated AMP-activated protein kinase （p-AMPK）， nuclear respiratory factor 1 （Nrf1）， and mitochondrial transcription factor A （TFAM） protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group， rats in the model group had a reduced number of platform crossings （P<0.01）， significantly prolonged evasion latency （P<0.01）， disorganized neuronal arrangement in the hippocampal region， widened gaps， and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light， and the number was reduced with severe loss. Mitochondria were atrophied， and cristae were lost. Severe damage was observed. The content of ROS was increased， and the level of ATP was decreased. mtDNA copy number decreased significantly （P<0.01）， and the protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM decreased （P<0.05， P<0.01）. Compared with those in the model group， rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform （P<0.01）， increased number of platform crossings （P<0.01）， restored mitochondrial morphology and structure of the hippocampal neurons， alleviated neuronal death， increased number of nissl bodies， weaken degree of injury， lower content of ROS， and significantly increased levels of ATP and number of copies of mtDNA （P<0.05， P<0.01）. In addition， there was increased protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05， P<0.01）. Compared with the model group， the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills （P<0.01）， and the number of platform crossings was increased， but the difference was not statistically significant. The mitochondria were swollen and deformed， and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly， and the number of nissl bodies was increased but not statistically significant. The ROS content decreased （P<0.01）， but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased （P<0.05）， but there was no significant difference in the protein expression of p-AMPK， Nrf1， and TFAM， and the results were not statistically significant. Compared with the donepezil hydrochloride group， there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills， and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills， rats in the combination group had a significantly lower number of platform crossings （P<0.01）， a significantly longer evasion latency （P<0.01）， a reduced number of neuronal cells， disorganized tissue structure， swollen and blurred cell outlines， a significant reduction in the number of nissl bodies. Moreover， there was an increase in the content of ROS， a decrease in the level of ATP and the number of mtDNA copies （P<0.01）， and a decrease in the expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05）. ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway， promoting mitochondrial biogenesis， and attenuating pathological damage to neurons in the hippocampal region， thereby demonstrating its therapeutic potential.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C （SFTPC） and lung injury induced by chronic intermittent hypoxia （CIH） and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups： a normoxia group， a CIH group， and low-， medium-， and high-dose Buzhong Yiqitang groups， with eight mice in each group. During the modeling， mice in the normoxia group were housed under standard oxygen concentrations， while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session， mice in the low-， medium-， and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses （8.1， 16.2， 32.4 g·kg^-1·d^-1 of crude drug， respectively）， while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung tissue were evaluated using hematoxylin-eosin （HE） staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Protein expression of SFTPC， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase R-like endoplasmic reticulum kinase （PERK）， phosphorylated PERK （p-PERK）， eukaryotic initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， activating transcript factor 4 （ATF4）， and CCAAT/enhancer-binding protein homologous protein （CHOP） in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group， mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels increased， while SFTPC expression in lung tissue was reduced （P<0.05， P<0.01）. The rate of apoptotic cells in lung tissue increased， and the expression of endoplasmic reticulum stress markers p-PERK， p-eIF2α， ATF4， and CHOP was upregulated （P<0.05， P<0.01）. Compared with the CIH group， Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels were decreased， and lung tissue SFTPC expression was recovered （P<0.05， P<0.01）. The apoptotic rate of lung tissue cells was significantly reduced， with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression （P<0.05， P<0.01）. Activation and expression of p-PERK， p-eIF2α， ATF4， and CHOP were also decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion， which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

BACKGROUND:In the treatment strategy of chronic osteomyelitis,the local antibiotic slow-release system has attracted much attention in the clinic due to the long-term release of effective concentrations of antibiotics to control the infection,and at the same time,the ability to repair bone defects caused by debridement. OBJECTIVE:To summarize the research status of antibiotic sustained-release carriers prepared from biodegradable polymer-based materials for the treatment of osteomyelitis,and analyze the limitations and challenges. METHODS:Chinese and English key words were"polymer,composite material,osteomyelitis,infectious bone defect,drug delivery systems,antibiotic sustained-release system,3D printing".Relevant articles were searched in PubMed,Web of Science,CNKI,and WanFang databases from January 2015 to August 2023.4 351 articles were obtained in the initial examination,and 87 articles were analyzed after screening. RESULTS AND CONCLUSION:Polymer-based materials have been widely studied in the preparation of antibiotic sustained-release carriers due to their good biocompatibility,biodegradability,thermal stability,and easy processing.However,the antibiotic slow-release carrier composed of a single polymer material cannot meet the standard of infectious bone defect repair materials due to the lack of biomechanical properties.The organic-inorganic composite material carrier,which simulates the formation of natural bone tissue structure,is expected to meet this standard.3D printing technology can precisely control the size,geometry,and spatial distribution of the interconnecting pores of the carrier,and can load the effective concentration of antibiotics to achieve controlled release.The polymer material is the most suitable for 3D printing because of its good thermal stability and plasticity.Therefore,the author believes that on the basis of new biodegradable organic-inorganic composite materials and combined with 3D printing technology,the material-structure-function integrated composite antibiotic slow-release carrier to simulate the extracellular matrix microenvironment is expected to become a novel research direction in the treatment of chronic osteomyelitis.

Objective To investigate the dyadic coping experience of patients undergoing cancer surgery and their spouses.Methods Sixteen cancer patients who were initially diagnosed with cancer and underwent cancer surgery in a general hospital in Henan province as well as and their spouses were selected as the study subjects by objective sampling method.All the patients and their spouses were included in the postoperative follow-up for dyadic coping experiences though a 3 months interview.The acquired data were summarised and analysed by Colaizzi's phenomenological method to identify relevant themes.Results A total of eight themes were identified,including three themes over the phase of confirmed diagnosis,strong stress response,coping with stress alone and consistent attitude towards seeking medical treatment;two themes over the perioperative phase,lack of coping ability and change in relationship;and three themes over the phase of home recovery,lack of disease information,poor communication skills and post-trauma growth of both patient and spouse.Conclusions The dyadic coping experience of patients who undergo cancer surgery and their spouses varies with the stages across the treatment.Therefore,medical staff should offer targeted nursing care according to the dyadic coping experience at different stages,hence to improve the physical and mental health of the cancer patients and their spouses.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To explore the changes in macular microcirculation status and visual function in patients with normal tension glaucoma(NTG)using the optical coherence tomography angiography(OCTA)and microperimeter MP-3 and analyze the correlation between the two.Methods In this cross-sectional observational study,17 NTG patients(30 eyes)were collected as the NTG group and then divided into mild,moderate and severe NTG subgroups according to the severity of the disease.During the same period,13 healthy subjects(23 eyes)with the same age and gender distribution were selected as the control group.OCTA was used to obtain linear density(LD)and perfusion density(PD)of superficial retinal vessels in the macular area.The microperimeter MP-3 was used to measure retinal sensitivity(RS)within 10° and fixation rate at 2° and 4° of the macular area.The OCTA parameters and microperimeter MP-3 parameters were compared among all groups,and the correlation between OCTA parameters and microperimeter MP-3 parameters in NTG patients was analyzed.Results There were no significant differences in LD and PD between the control group and the mild NTG sub-group in the central and nasal sides of the macula;the LD and PD in the remaining regions and overall average LD and PD showed a gradual downward trend in the control group and the mild,moderate and severe NTG subgroups.Compared with the control group,the RS of the mild NTG subgroup was lower in the inferior and temporal regions of the macular area.The RS of each region and overall average RS in the macular area decreased with the aggravation of the NTG.In the NTG group,LD and PD were significantly positively correlated with RS in each region and overall average RS in the macular area(all P＜0.05).In the NTG group,LD and PD were positively correlated with P2 in some regions of the macular area.Con-clusion Compared with the control group,the macular microcirculation status and visual function of NTG patients signif-icantly decreased with the progression of the disease;there is a significant correlation between macular LD and RS in NTG patients.