Sangjuyin， as a pungent and cooling agent with precise therapeutic effect， is a classic pungent formula for cooling relief of the epidermis， which is highly respected by medical practitioners. This formula is from the Wenbing Tiaobian written by WU Jutong in the Qing dynasty， on the basis of which subsequent medical practitioners have made additions and subtractions to apply it. The authors used the bibliometric method to systematically organize the medical books from the Qing dynasty and the Republic of China and modern literature to analyze the composition， concoction， decoction， efficacy， and previous and modern application of Sangjuyin. After examination， the drug base of this formula is basically clear. Armeniacae Semen Amarum is the dried mature seeds of Armeniaca vulgaris， family Rosaceae. Forsythiae Fructus is the dried fruit of Forsythia suspensa， family Mulleinaceae. Menthae Haplocalycis Herba is the dried above-ground part of Mentha haplocalyx， family Labiatae. Mori Folium is the dried leaves of Morus alba， family Moraceae. Chrysanthemi Flos is the dried head of Chrysanthemum morifolium， family Asteraceae. Platycodonis Radix is the dried root of Eryngium grandiflorum， family Eryngium. Glycyrrhizae Radix et Rhizoma is the dried root and rhizome of Glycyrrhiza uralensis of the Leguminosae family， and Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis of the Gramineae family. It is recommended that the eight drugs be used in raw form as medicine. The dosage and method of decoction were converted into a modern single dosage of 7.46 g Armeniacae Semen Amarum， 5.60 g Forsythiae Fructus， 2.98 g Menthae Haplocalycis Herba， 9.33 g Mori Folium， 3.73 g Chrysanthemi Flos， 7.46 g Platycodonis Radix， 2.98 g Glycyrrhizae Radix et Rhizoma， and 11.19 g Phragmitis Rhizoma， with 400 mL water added， and the solution was boiled to obtain 200 mL， taken twice a day. Sangjuyin has the efficacy of dispersing wind and clearing heat， promoting lung and relieving cough， and it is used for treating the initial onset of wind-warmth and the evidence of evil spirits in the lungs and collaterals. Modern research has shown that Sangjuyin is often used in the treatment of cough， pneumonia， rhinitis， and other respiratory diseases， and the results of this study provide a reference for the later development of Sangjuyin.

ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

Amyotrophic lateral sclerosis (ALS) is a chronic, progressive degenerative disease affecting both upper and lower motor neurons, primarily characterized by skeletal muscle weakness and atrophy. Notably, the same muscle group may exhibit asynchronous involvement. This study aims to investigate the involvement patterns of the orbicularis oculi (OOc) and orbicularis oris (OOr) in ALS patients, compare the findings with healthy controls (HCs) and myasthenia gravis (MG) patients, and explore the characteristics and clinical significance of facial muscle involvement in ALS.

Background Ozone (O₃), a key air pollutant, significantly contributes to cardiovascular disease (CVD)-related mortality, with particularly pronounced effects in the elderly. Objective To explore the association between acute O₃ exposure and mortality from CVD and its subtypes in the elderly population in Jinan, and to investigate the modifying effects of gender,age, and seasonal factors on O₃-related effects, as well as to clarify the interaction with other air pollutants. Methods Daily mortality data for CVD, air pollutants, and meteorological parameters were collected in Jinan from 2015 to 2023. Generalized additive models (GAM) combined with distributed lag nonlinear models (DLNM) were used to analyze the lag effects of acute O₃ exposure on mortalities from CVD, ischemic heart disease (IHD), and stroke in elderly individuals aged ≥60 years. Subgroup analyses were conducted to explore effect differences by gender (male vs. female), age (non-high-aged elderly<80 years vs. high-aged elderly ≥80 years), and season (warm season: April–September vs. cold season: October–March of the following year). Relative excess risk due to interaction (RERI), attributable proportion of interaction (API), and Synergy index (SI) were used to assess the interactions of O₃ with PM_2.5 and NO₂. Results During the study period, the mean daily concentration of ozone reached (105.01 ± 54.18) μg·m⁻³, exceeding the Grade I limit value specified in Ambient Air Quality Standard (GB 3095–2012). Among the 203834 CVD deaths, IHD (53.07%) and stroke (33.33%) were the predominant mortality subtypes. The single-day lag analysis revealed peak excess risk (ER) for CVD mortality at lag0 (ER=0.64%, 95%CI: 0.29%, 1.00%) per 10 μg·m⁻³ O₃ increase. The cumulative effects peaked at lag04 (ER=1.61%, 95%CI: 0.77%, 2.46%). The subtype-specific analyses showed the maximal single-day effects at lag0 were identified for both IHD (ER=0.61%, 95%CI: 0.20%, 1.03%) and stroke (ER=0.65%, 95%CI: 0.19%, 1.11%), while the cumulative risks peaked at lag04 for IHD (ER=1.54%, 95%CI: 0.56%, 2.54%) and lag03 for stroke (ER=1.74%, 95%CI: 0.76%, 2.73%). The gender subgroup analyses suggested that both male and female subgroups showed the most significant impact on CVD mortality at lag0, with ER values of 0.53% (95%CI: 0.11%, 0.95%) and 0.75% (95%CI: 0.33%, 1.18%), respectively, but the differences were not statistically significant (P>0.05). No statistically significant difference in effect values was found between high-aged and non-high-aged elderly (P>0.05) after age subgroup analyses. The seasonal subgroup analyses indicated that the effects of O₃ on CVD and its subtypes in the warm season were significantly higher than those in the cold season (P<0.05). At lag0 in the warm season, the ER values for CVD, IHD, and stroke mortality were 0.86% (95%CI: 0.57%, 1.14%), 0.84% (95%CI: 0.49%, 1.19%), and 0.84% (95%CI: 0.43%, 1.26%), respectively. The interaction analyses revealed an antagonistic effect between O₃ and PM_2.5 on stroke mortality in the elderly [RERI=−4.64% (95%CI: −9.27%, −0.01%), API=−4.39% (95%CI: −8.77%, −0.01%), SI=0.55 (95%CI: 0.26, 0.84)]. The O₃ effect remained robust in the multi-pollutant models (P<0.05). Conclusion Acute O₃ exposure increases the risk of mortality from CVD and its subtypes in the elderly, and this effect is amplified in the warm season. Additionally, O₃ and PM_2.5 have an antagonistic effect on stroke mortality in the elderly.

Alzheimer's disease(AD)is a progressive neurodegenerative disease with hidden onset.Recent researches have shown that apolipoprotein E4(APOE4)is a high-risk genetic factor of AD,and the clinical symptoms in APOE4 genotype AD patients are closely related to metabolic disorders.This paper reviewed the role of APOE4 in the pathogenesis of AD,and it is indicated that APOE4 contributes to the injury of the cerebral blood-brain barrier,is associated with the disorder of cerebral glucose and lipid metabolism,and leads to the damage of the scavenging ability of microglia.Moreover,this paper explored the approach of early intervention of AD with traditional Chinese medicine(TCM)based on the APOE4 pathogenesis.Based on the pathogenesis of AD being deficiency in origin and excess in superficiality,and under the guidance of the principle of prevention before illness in TCM,it is proposed that early TCM intervention for APOE4 genotype AD patients with metabolic disorders can be performed through improving the phlegm-dampness constitution,by focusing on insulin resistance-related indicators,and with traditional Chinese drug therapy based on syndrome differentiation alone or together with comprehensive management of exercises,diet control and drug interventions,thus to reduce or delay the onset of APOE4 genotype AD.

BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.