Research progress of airway inflammation in asthma: A bibliometric analysis.

BACKGROUND: In recent years, the prevalence of asthma has gradually increased and the number of asthmatics worldwide has reached 358 million, which has caused huge economic loss. Airway inflammation is an important feature of asthma, and international research in this field has a high degree of heat. Therefore, this paper uses the bibliometric method to systematically review and visualize the literature in this field, aiming to provide some reference value for follow-up related research. METHODS: To retrieve the research literature on airway inflammation in asthma from 2003 to 2022 in the Web of Science Core Collection database. The bibliometric method was used to systematically analyze the included literature data by using visualization analysis software such as CiteSpace (6.2. R4) and VOSviewer (1.6.19). RESULTS: A total of 1892 articles published in 423 journals were included in this study, from 1912 institutions in 62 countries/regions. The number of articles published between 2003 and 2022 showed a trend of fluctuating growth. The country with the largest number of articles published was China (558,29.49 %), followed by the United States (371,19.61 %) and Korea (212,11.21 %). Gibson, Peter G is the author with the highest number of publications, and Journal of Allergy and Clinical Immunology is the most published journal. CONCLUSION SUBSECTIONS: This study systematically reveals the state of the literature in the field of airway inflammation in asthma over the past 20 years. The exploration of inflammatory cell components, pathway molecules and biological agents are research hotspots in this field and should be further studied.

Characterization and In vivo Evaluation of Polymorphic Valnemulin Hydrogen Fumarate.

AIMS: In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in Actinobacillus pleuropneumoniae-induced pneumonia in mice. METHOD: Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an in vitro antimicrobial susceptibility test. RESULTS: The valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug (tiamulin fumarate) in an Actinobacillus pleuropneumoniae challenge-treatment trial. CONCLUSION: Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Glyphosate exposure affected longevity-related pathways and reduced survival in asian honey bees (Apis cerana).

Glyphosate (N-(phosphonomethyl)glycine, GLY) ranks among the most extensively used and effective herbicides globally. However, excessive GLY utilization poses a substantial threat to the survival of honey bees (Apis cerana). Here we monitored the survival status of A. cerana treated with GLY, and conducted transcriptome sequencing of the bee gut and head to further explore potential GLY influences at the molecular level. We observed that the mortality rate of bees increased as GLY concentration escalated. Pivotal pathways emerged in response to the GLY treatment, with a substantial number of differentially expressed genes enriched in the longevity regulating pathway - multiple species. This strongly suggested that GLY may influence the physiological behavior of bees by impacting this particular pathway. Moreover, our analysis revealed a notable reduction in the enzymatic activities of CYP450 and AChE in both the bee head and intestines of when exposed to GLY. Conversely, the enzymatic activity of superoxide dismutase (SOD) in the head remained unaffected, whereas in the intestines, it exhibited a significant increase. Additionally, prophenol oxidase (PPO) and glutathione-S-transferases (GSTs) displayed contrasting trends in enzymatic activity in both organs. This study offers valuable insights into how GLY impacted the survival of A. cerana.

Antibiotic-loaded bone cement enhances ability of tibial cortex transverse transport for treating infected wounds / 中国组织工程研究

BACKGROUND:Diabetic foot patients with wound infections constitute a large patient population,and there is currently no satisfactory treatment approach. OBJECTIVE:To investigate the clinical efficacy of a modified tibial cortex transverse transport combined with antibiotic-loaded bone cement for treating refractory diabetic foot ulcers. METHODS:A total of 46 diabetic foot ulcers patients,27 males and 19 females,with an average age of 64.37 years,were selected from Beijing Chaoyang Hospital,Capital Medical University and Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from January 2020 to January 2023.All of them underwent the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement treatment.Ankle-brachial index,WIFi(Wound/Ischemia/Foot infection)classification,pain visual analog scale score,and ulcer area were recorded before and 3 months after surgery. RESULTS AND CONCLUSION:(1)The mean ulcer healing time for the 46 patients was(58.07±24.82)days.At 3 months postoperatively,there were significant improvements in ankle-brachial index,pain visual analog scale score,ulcer area,and WIFi classification in 46 patients,as compared to the preoperative values,with statistically significant differences(P<0.05).Two patients experienced pin-tract infections,without infection or ulcer recurrence during the follow-up period.(2)These findings indicate that the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement effectively alleviates patients'pain,improves lower limb circulation,controls infections,and promotes ulcer healing.

Establishment and validation of a prediction model of hip fracture risk factors in elderly stroke patients / 中国组织工程研究

BACKGROUND:Prevention of fractures after stroke is very important,and there are currently no models to predict the occurrence of hip fractures after stroke. OBJECTIVE:To investigate the risk factors leading to hip fracture in stroke patients and to establish a risk prediction model to visualize this risk. METHODS:A total of 439 stroke patients were selected from the Affiliated Hospital of Xuzhou Medical University from June 2014 to June 2017,including 107 males and 332 females,with a mean age of(71.38±9.74)years.They were divided into fracture group(n=35)and non-fracture group(n=404)according to the presence or absence of hip fracture.Univariate and multivariate analyses were used to determine the risk factors for hip fracture after stroke.The data were randomly divided into training set(70%)and test set(30%).Nomogram predicting the risk of hip fracture occurrence was created based on the results of the multifactor analysis,and performance was evaluated using receiver operating characteristic curve,calibration curves,and decision curve analysis.A web calculator was created to facilitate a more convenient interactive experience for clinicians. RESULTS AND CONCLUSION:(1)Univariate analysis showed significant differences between the two groups in the number of falls,smoking,hypertension,glucocorticoids,number of strokes,Mini-Mental State Examination,visual acuity level,National Institute of Health Stroke Scale,Berg Balance Scale,and Stop Walking When Talking scale scores(P<0.05).(2)Multivariate analysis showed that number of falls[OR=17.104,95%CI(3.727-78.489),P=0.000],National Institute of Health Stroke Scale[OR=1.565,95%CI(1.193-2.052),P=0.001],Stop Walking When Talking[OR=12.080,95%CI(2.398-60.851),P=0.003]were independent risk factors positively associated with new hip fractures.Bone mineral density[OR=0.155,95%CI(0.044-0.546),P=0.012]and Berg Balance Scale[OR=0.840,95%CI(0.739-0.954),P=0.007]were negatively associated with new hip fractures after stroke.(3)The AUC values of nomogram were 0.956 and 0.907 in the training and test sets,respectively,and the calibration curves showed a high agreement between predicted and actual status with an area under the decision curve of 0.038 and 0.030,respectively.(4)These findings conclude that the number of falls,low bone mineral density,low Berg Balance Scale score,high National Institute of Health Stroke Scale score,and positive Stop Walking When Talking are risk factors for hip fracture after stroke.Based on this,a nomogram with high accuracy was developed and a web calculator(https://stroke.shinyapps.io/DynNomapp/)was created.

Establishing N-ELISA-based method for rapid detection of neutralizing antibodies against respiratory syncytial virus / 中华微生物学和免疫学杂志

Objective:To prepare rabbit polyclonal antibodies against respiratory syncytial virus (RSV) N protein and use them as the detection antibodies to establish a N-ELISA-based method for rapid detection of neutralizing antibodies.Methods:A plasmid of pET30a-N for the expression of RSV N protein was constructed. After purification, the protein was immunized into New Zealand rabbits to prepare polyclonal antibodies, which were used as the detection antibodies. Positive serum samples were diluted and used to neutralize RSV (100 TCID 50/well). Hep-2 cells were inoculated and cultured, and then the cells were fixed with 80% acetone. ELISA was performed to detect RSV N protein in infected cells. When the absorbance value of a well was below the cut-off value, it was regarded as the positive well in the neutralization test. The highest dilution of a positive well serum was the neutralizing antibody titer. After optimizting the antibody dilution, detection time, cell density and the duration of neutralization, the method for neutralizing antibody detection was established based on N-ELISA. The established method was verified by analyzing the influences of different cell generations and edge effects, and calculating the accuracy, repeatability and precision. The correlation between the established method and microneutralization method was analyzed by detecting human RSV IgG-positive serum. Results:The plasmid pET30a-N was successfully constructed, and the expressed N protein showed high purity and good specificity. After the third immunization, the antibody titer in rabbit serum was 1∶51 200, and the antibodies could specifically bind to RSV. The prepared rabbit anti-RSV N polyclonal antibodies had a titer of 1∶51 200, and showed good specificity. The neutralizing antibodies could be detected on day 4 with the established method, and the duration of neutralization was shortened to 30 min. Cell generations and the position of wells in the 96-well plate (edge well and non-edge well) had no significant effect on the method, and the repeatability, precision and accuracy of the method were good. In the detection of 64 RSV IgG-positive human serum samples by the established method and microneutralization method, the correlation coefficient was 0.929 6, indicating a good positive correlation between the two methods.Conclusions:A N-ELISA-based method for rapid neutralizing antibody detection is successfully established, which can be used to evaluate the serum antibody level after RSV vaccination.

Correlations of brain network functional connectivity alterations with cerebrospinal fluid pathological markers in patients with Alzheimer's disease / 中华神经医学杂志

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Current Situation of Health Technology Assessment in Traditional Chinese Medicine Hospitals / 中国实验方剂学杂志

ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine （TCM） hospitals on hospital-based health technology assessment （HB-HTA）， assessment needs， challenges， and suggestions， so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered， and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations （F=0.251； P=0.778）. The practitioners in Hong Kong， Macao， and Taiwan had lower recognition than those in other regions. In terms of the assessment needs， 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces （5.91） and TCM appropriate technology （5.57） had higher assessment priority scores. The assessment needs were high for the effectiveness （235 practitioners） and safety （224 practitioners） of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future， while the work might face challenges such as the lack of organizations and system and the shortage of talents， which requires policy support.

Berberine interferes with RSV infection of HEp-2 cells by inducing mitophagy autophagy / 中国药理学通报

Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

Construction of Knowledge Graph Based on Literature Data by Taking Treatment of Diabetic Peripheral Neuropathy with Traditional Chinese Medicine as An Example / 中国实验方剂学杂志

ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine（TCM） treatment of diabetic peripheral neuropathy（DPN）， to construct of the knowledge map of TCM treatment of DPN， and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source， TCM-related concepts and entities were constructed by manual citation， and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7， and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic， defined 12 node labels such as prescriptions， Chinese medicines and syndrome types at the schema layer， as well as 4 types of relationships， such as inclusion， correspondence， selection and composition. It could support the query and discovery of nodes（syndrome elements， syndrome types and treatment methods）， as well as the relationship between each node. ConclusionBased on the literature data， this study constructed a knowledge map for TCM treatment of DPN， which brought together various methods of TCM treatment of DPN， including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis， syndrome type composition to treatment method selection， which can provide new ideas and methods for literature data to serve clinical and scientific research work， as well as reference for visualization of TCM literature knowledge， intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.

Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury transforming growth factor beta1 signaling and metabolic reprogramming.

OBJECTIVE: To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-ß1)/Smads signaling pathway. METHODS: One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-ß signaling molecules including TGF-ß1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer. RESULTS: Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all P < 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-ß1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all P < 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis. CONCLUSION: Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-ß1 inactivation and metabolic reprogramming.

Efficacy of bioactive compounds of Chaihu () on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway.

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.

Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma.

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.

Neoadjuvant immunotherapy in patients with pulmonary lymphoepithelioma-like carcinoma.

OBJECTIVES: Neoadjuvant immunotherapy can be used to treat early-stage non-small-cell lung cancer; however, their effects on pulmonary lymphoepithelioma-like carcinomas (LELC) remain unclear. MATERIALS AND METHODS: Thirty-nine patients with stages I-III LELC were treated with chemotherapy (Chemo) or neoadjuvant immune-checkpoint inhibitors (ICIs) with or without chemo (IO) before radical-intent surgery. Short-term outcomes included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (PCR), and event-free survival. For comparison, we used IO to treat 63 patients with pulmonary squamous cell carcinomas (SQC) and 47 with adenocarcinomas (ADC). Propensity score matching was analyzed to minimize bias. RESULTS: ORRs of the LELC-IO and LELC-Chemo groups were 62.5% and 42.9%, respectively (odds ratio, 2.2, 95% confidence interval, 0.423-11.678, p = 0.346). Seven (21.9%) and zero patients in LELC-IO and LELC-Chemo groups, respectively, reached PCR. MPR was identified in five (15.6%) of the 32 patients with LELC-IO. The 1-year progression-free survival rates were 96.9% and 71.4% in IO and Chemo groups, respectively (p > 0.05). However, no difference was observed in ORR, PCR, and MPR between LELC and SQC groups (ORR, 63.2% vs. 68.4%, p > 0.05; PCR, 21.1% vs. 47.4, p > 0.05; MPR, 42.1% vs. 57.9%, p > 0.05) and LELC and ADC groups (ORR, 58.8% vs. 41.2%, p > 0.05; PCR, 17.6% vs. 23.5%, p = 0.672; MPR, 29.4% vs. 47.1%, p > 0.05). The plasma Epstein-Barr virus (EBV) DNA level in a patient was altered posttreatment. CONCLUSION: Patients with LELC could be benefit from neoadjuvant immunotherapy. Distinct histological subtypes demonstrated comparable efficacy with respect to neoadjuvant immunotherapy.

Morphology and deformity of the shoulder and pelvis in the entire spine radiographs of adolescent idiopathic scoliosis.

Background: To investigate the deformity and asymmetry of the shoulder and pelvis in adolescent idiopathic scoliosis (AIS) patients. Methods: This retrospective cross-sectional study enrolled 223 AIS patients with a right thoracic curve or left thoracolumbar/lumbar curve who underwent spine radiographs at the Third Hospital of Hebei Medical University between November 2020 and December 2021. The following parameters were measured: Cobb angle, clavicular angle, glenoid obliquity angle, acromioclavicular joint deviation, femoral neck-shaft projection angle, iliac obliquity angle, acetabular obliquity angle, coronal trunk deviation distance, and spinal deformity deviation distance. The Mann-Whitney U test, Kruskal-Wallis H test were used for inter-group comparisons, and Wilcoxon signed-rank test were used for intra-group left and right sides comparisons. Results: Shoulder and pelvic imbalances were found in 134 and 120 patients, respectively, and there were 87, 109, and 27 cases of mild, moderate, and severe scoliosis, respectively. Compared with mild scoliosis patients, the difference in the acromioclavicular joint offset on bilateral sides was significantly increased in moderate and severe scoliosis [11.04, 95% confidence interval (CI): 0.09-0.14 for mild, 0.13-0.17 for moderate, and 0.15-0.27 for severe scoliosis, P=0.004], and the difference in the femoral neck-shaft projection angle on bilateral sides was significantly enhanced with scoliosis aggravation (14.14, 95% CI: 2.34-3.41 for mild, 3.00-3.94 for moderate, and 3.57-6.43 for severe scoliosis, P=0.001). The acromioclavicular joint offset was significantly larger on the left than that on the right in patients with a thoracic curve or double curves (thoracic curve -2.75, 95% CI: 0.57-0.69 for the left and 0.50-0.63 for the right, P=0.006; double curve -3.27, 95% CI: 0.60-0.77 for the left and 0.48-0.65 for the right, P=0.001). The femoral neck-shaft projection angle was significantly larger on the left than right in patients with a thoracic curve (-4.46, 95% CI: 133.78-136.20 for the left and 131.62-134.01 for the right, P<0.001), but larger on the right than left in patients with thoracolumbar/lumbar curve (thoracolumbar -2.98, 95% CI: 133.75-136.70 for the left and 135.13-137.82 for the right, P=0.003; lumbar -3.24, 131.97-134.56 for the left and 133.76-136.26 for the right, P=0.001). Conclusions: In AIS patients, shoulder imbalance has a greater impact on coronal balance and spinal scoliosis above the lumbar segment, whereas pelvic imbalance has a greater impact on sagittal balance and spinal scoliosis below the thoracic segment.

Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.

The lens is transparent, non-vascular, elastic and wrapped in a transparent capsule. The lens oppacity of AQP5-/- mice was increased more than that of wild-type (AQP5+/+ ) mice. In this study, we explored the potential functional role of circular RNAs (circRNAs) and transcription factor HSF4 in lens opacity in aquaporin 5 (AQP5) knockout (AQP5-/- ) mice. Autophagy was impaired in the lens tissues of AQP5-/- mice. Autophagic lysosomes in lens epithelial cells of AQP5-/- mice were increased compared with AQP5+/+ mice, based on analysis by transmission electron microscopy. The genetic information of the mice lens was obtained by high-throughput sequencing, and then the downstream genes were analysed. A circRNA-miRNA-mRNA network related to lysosomal pathway was constructed by the bioinformatics analysis of the differentially expressed circRNAs. Based on the prediction of the TargetScan website and the validation by dual luciferase reporter assay and RNA immunoprecipitation-qPCR, we found that circRNA (Chr16: 33421321-33468183+) inhibited the function of HSF4 by sponging microRNA (miR-149-5p), and it downregulated the normal expression of lysosome-related mRNAs. The accumulation of autophagic lysosome may be one of the reasons for the abnormal development of the lens in AQP5-/- mice.

Baitouweng Tang Suppresses Colorectal Cancer HCT116 Cells by Regulating Hedgehog Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Baitouweng Tang （BTWT） on the apoptosis of human colorectal cancer HCT116 cells and decipher the underlying mechanism based on the Hedgehog （Hh） signaling pathway. MethodHCT116 cells were treated with BTWT （25， 50， 100， 200， 500， 750， and 1 000 mg·L-1） for 24 h， and then the cell proliferation was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. Five groups were designed for the treatment of HCT116 cells， including a blank control group， BTWT groups （125， 250， and 500 mg·L-1）， and a positive control （5-fluorouracil， 5-FU， 40 mmol·L-1） group. The cell morphology was observed under an inverted microscope. The migration of the cells was detected by scratch test， and the apoptosis by Hoechest 33324/propidium iodide （PI） staining and flow cytometry. Western blot was employed to determine the protein levels of sonic hedgehog （SHh）， GLI family zinc finger protein 1 （Gli1）， smoothened （Smo）， suppressor of fused （SuFu）， cellular-myelocytomatosis viral oncogene （c-Myc）， and the apoptosis-related proteins B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. The quantitative real-time reverse transcription PCR （Real-time PCR） was employed to determine the mRNA levels of Bax， Bcl-2， SHh， Gli1， Smo， SuFu， and c-Myc. ResultCompared with the blank control group， BTWT changed the cell morphology （making the cell become round with dense nucleus）， inhibited the proliferation of HCT116 cells in a dose-dependent manner， decreased the ability of migration （P<0.05， P<0.01）， and increased apoptotic cells. Compared with the blank control group， BTWT （500 mg·L-1） treatment for 24 h up-regulated the protein and mRNA levels of Bax （P<0.05， P<0.01） and down-regulated the protein and mRNA levels of Bcl-2 in HCT116 cells （P<0.05， P<0.01）. Moreover， the treatment down-regulated the mRNA and protein levels of SHh， Gli1， Smo， and c-Myc （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SuFu （P<0.05， P<0.01）. ConclusionBTWT inhibited the proliferation and migration and induced the apoptosis of colorectal cancer HCT116 cells by down-regulating the Hh signaling pathway.

Clinical Application Analysis of Da Qinjiaotang Based on Ancient and Modern Literature / 中国实验方剂学杂志

Da Qinjiaotang is a common classical prescription for the treatment of stroke. It originates from Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the Basic Questions （《素问病机气宜保命集》） by physician LIU Wansu， and is composed of Gentianae Macrophyllae Radix， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Asari Radix et Rhizoma， Notopterygii Rhizoma et Radix， Saposhnikoviae Radix， Scutellariae Radix， Gypsum Fibrosum， Angelicae Dahuricae Radix， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. Doctors of all dynasties have disputed the composition principle of the prescription and argued whether its treatment of stroke belongs to the theory of "internal wind" or "external wind". Through collating and analyzing ancient and modern literature related to the indications of Da Qinjiaotang， this paper was dedicated to the origin of syndrome differentiation and treatment of Da Qinjiaotang. According to LIU Wansu's original works， Da Qinjiaotang is a prescription for the treatment of "internal wind"， and in the prescription， wind medicinal herbs such as Gentianae Macrophyllae Radix， Notopterygii Rhizoma et Radix and Angelicae Pubescentis Radix removes stagnation， clears sweat pore， and makes qi and blood channels flow smoothly. However， later generations， affected by the idea of "external wind"， believe that this prescription is used for the treatment of "external wind". Ancient physicians gradually supplemented the symptoms of stroke， such as wry eye and mouth， hemibody pain and limb numbness， which were treated by Da Qinjiaotang， and Da Qinjiaotang was also applied to the treatment of other diseases， such as tendon dryness， convulsion and arthralgia. Modern doctors still explain the disease pathogenesis from the theory of "external wind" as deficiency in channels and collaterals and the entry of pathogenic wind， and the prescription has the effect of dispersing wind， clearing heat and nourishing and activating blood. In clinical practice， Da Qinjiaotang is mainly used to treat cerebrovascular diseases and peripheral facial paralysis in nervous system diseases， gouty arthritis and rheumatic arthritis in the rheumatic immune system and skin diseases. The above findings facilitate the research and development of Da Qinjiaotang.

Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis / 中国中药杂志

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.