ObjectiveTo investigate the neuroprotective mechanism of baicalein （BAI） on Parkinson's disease （PD） model rats by regulating endoplasmic reticulum stress pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into normal group， model group， BAI low-dose group （80 mg·kg^-1）， medium-dose group （120 mg·kg^-1）， high-dose group （160 mg·kg^-1）， and levodopa-benserazide group （51 mg·kg^-1）， with 12 rats per group. Except for the normal group， PD rat models were established by subcutaneous injection of rotenone solution （2 mg·kg^-1） into the neck back of rats in the rest of groups for consecutive 28 days. Concurrently， rats in all groups received corresponding drugs via gavage for 28 days. After treatment， behavioral changes were assessed by using the open field and pole climbing tests. Neuronal pathology and apoptosis in the substantia nigra were observed via hematoxylin-eosin （HE） staining and TdT-mediated dUTP nick-end labeling （TUNEL） assay. α-Synuclein and tyrosine hydroxylase （TH） expressions were detected by immunohistochemistry （IHC）. Inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. RNA-like endoplasmic reticulum kinase （PERK）， activating transcription factor 4 （ATF4）， C/EBP-homologous protein （CHOP）， and Bcl-2-associated X protein （Bax） expressions were analyzed by Western blot. ResultsCompared with the normal group， the model group exhibited significantly reduced locomotion distance （P<0.01） and elevated pole-climbing scores （P<0.01）， with increased neuronal apoptosis rate （P<0.01）， significantly enhanced α-Synuclein expression （P<0.01）， decreased TH expression （P<0.01）， upregulated release of inflammatory factors （P<0.05，P<0.01）， and increased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. Compared with the model group， medium/high-dose BAI groups and levodopa-benserazide group showed obviously improved motor function （P<0.05，P<0.01）， reduced pole-climbing scores （P<0.05）， decreased neuronal apoptosis （P<0.01）， downregulated α-Synuclein expression （P<0.01）， upregulated TH expression （P<0.05，P<0.01）， suppressed release of inflammatory factors （P<0.05，P<0.01）， and decreased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. ConclusionBAI reduces the release of neuroinflammatory factors and neuronal apoptosis to improve the neurological function of PD model rats， and its mechanism may be related to alleviating endoplasmic reticulum stress and apoptosis by regulating the PERK/ATF4 pathway.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

ObjectiveTo investigate the neuroprotective mechanism of baicalein （BAI） on Parkinson's disease （PD） model rats by regulating endoplasmic reticulum stress pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into normal group， model group， BAI low-dose group （80 mg·kg^-1）， medium-dose group （120 mg·kg^-1）， high-dose group （160 mg·kg^-1）， and levodopa-benserazide group （51 mg·kg^-1）， with 12 rats per group. Except for the normal group， PD rat models were established by subcutaneous injection of rotenone solution （2 mg·kg^-1） into the neck back of rats in the rest of groups for consecutive 28 days. Concurrently， rats in all groups received corresponding drugs via gavage for 28 days. After treatment， behavioral changes were assessed by using the open field and pole climbing tests. Neuronal pathology and apoptosis in the substantia nigra were observed via hematoxylin-eosin （HE） staining and TdT-mediated dUTP nick-end labeling （TUNEL） assay. α-Synuclein and tyrosine hydroxylase （TH） expressions were detected by immunohistochemistry （IHC）. Inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. RNA-like endoplasmic reticulum kinase （PERK）， activating transcription factor 4 （ATF4）， C/EBP-homologous protein （CHOP）， and Bcl-2-associated X protein （Bax） expressions were analyzed by Western blot. ResultsCompared with the normal group， the model group exhibited significantly reduced locomotion distance （P<0.01） and elevated pole-climbing scores （P<0.01）， with increased neuronal apoptosis rate （P<0.01）， significantly enhanced α-Synuclein expression （P<0.01）， decreased TH expression （P<0.01）， upregulated release of inflammatory factors （P<0.05，P<0.01）， and increased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. Compared with the model group， medium/high-dose BAI groups and levodopa-benserazide group showed obviously improved motor function （P<0.05，P<0.01）， reduced pole-climbing scores （P<0.05）， decreased neuronal apoptosis （P<0.01）， downregulated α-Synuclein expression （P<0.01）， upregulated TH expression （P<0.05，P<0.01）， suppressed release of inflammatory factors （P<0.05，P<0.01）， and decreased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. ConclusionBAI reduces the release of neuroinflammatory factors and neuronal apoptosis to improve the neurological function of PD model rats， and its mechanism may be related to alleviating endoplasmic reticulum stress and apoptosis by regulating the PERK/ATF4 pathway.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.