Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

OBJECTIVE To study the improvement effect and mechanism of sanguinarine （SG） on inflammatory pain in rats with lumbar disc herniation （LDH） and its mechanism. METHODS LDH model rats were established and divided into model group， SG low-dose， medium-dose and high-dose groups （1.00， 2.50， 6.25 mg/kg）， high-dose of SG+Anisomycin [mitogen-activated protein kinase （MAPK） activator] group （6.25 mg/kg SG+5 mg/kg Anisomycin）， with 10 rats in each group. Another 10 rats were included as the control group. Each group was given corresponding drugs intraperitoneally， while the control group and model group were given an equal volume of normal saline intraperitoneally， once a day， for 7 consecutive days. The general situation and neurological changes of rats in each group were observed， and the pain threshold [including paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL）] of rats was determined； the histopathological changes of dorsal root ganglion （DRG） were observed in rats. The serum levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and pain factors [neuropeptide Y （NPY）， 5-hydroxytryptamine （5-HT）] in rats were detected.The positive expressions of ionized-calcium binding adaptor molecule-1 （Iba-1） in spinal cord microglia and glial fibrillary acidic protein （GFAP） in astrocytes were observed. The expressions of proteins related to MAPK/extracellular signal-regulated kinase （ERK）/nuclear factor κB （NF-κB） signaling pathway， TNF-α and IL-1β proteins were detected in DRG tissue of rats. RESULTS Compared with the control group， the rats in the model group showed decreased appetite， hindlimb movement disorders， and disordered neuronal cell arrangement， the neurological score， the levels of TNF-α， IL-1β， NPY， the positive expressions of Iba-1 and GFAP， the phosphorylations of p38 MAPK， ERK1/2 and NF-κB p65， the protein expressions of TNF-α and IL-1β were significantly increased （P＜0.05）； PWMT， PWTL and the levels of 5-HT were significantly reduced （P＜0.05）. Compared with the model group， the rats of SG groups showed some relief in their mental appetite and hindlimb motor disorders， the intervertebral disc structure of DRG was restored， and the levels of the above quantitative indicators had significantly reversed （P＜0.05）. Anisomycin reversed the improvement effect of SG on inflammatory pain in LDH rats. CONCLUSIONS SG can improve inflammatory pain by inhibiting the activation of microglia in DRG tissue of LDH rats， reducing the release of inflammatory factors， and increasing pain threshold， and its mechanism of action may be related to the inhibition of MAPK/ERK/NF- κB signaling pathway.

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Cold and heat belong to the eight-principal syndrome differentiation of traditional Chinese medicine， which can reflect the rise and fall of Yin and Yang in the body and the Yin and Yang nature of the disease. At present， traditional Chinese medicine has an inconsistent understanding of cold and heat in acute coronary syndrome. The emphasis on pathogenic factors of cold and heat is biased， and the elements of cold and heat syndrome are not fully reflected in the scale. Therefore， the literature has been reviewed from the perspectives of etiology， pathogenesis， symptom elements， and test signs with drugs. From the perspective of etiology， both cold evil and heat evil can increase the risk of acute coronary syndrome. It was previously believed that acute coronary syndrome occurs frequently in cold climates such as winter and spring. Based on this understanding， hot weather can also induce acute coronary syndrome， and different temperatures have different effects on patients of different ages and with different underlying diseases. In addition， artificial pathogenic factors such as excessive consumption of cold food and refrigeration air conditioners were added. From the perspective of pathogenesis， on the basis of the traditional ''asthenia in origin and asthenia in superficiality'' and ''phlegm stagnation''， it is found that Yin-cold and fire-heat can both cause paralysis of the heart chakra and pain induced by the blockage. The pathogenesis of acute coronary syndrome characterized by heat stagnation and coldness featuring heartburn should be distinguished from gastroesophageal reflux disease. Moreover， the pathogenesis of Yin cold coagulation and pulse stagnation and wind obstruction are different. The acute coronary syndrome is in line with the wind characteristics of frequent changes and can be treated with wind medicine. From the perspective of syndrome elements， the syndrome elements such as cold condensation， heat accumulation， and toxicity are analyzed， and the use of basic syndrome elements and their combination forms facilitates clinical and scientific research. In addition， according to the test sign with the drug， it can be seen that the attributes of cold and heat of traditional Chinese medicine prescriptions for acute coronary syndrome can be explained according to the temperature-sensitive transient receptor potential （TRP） ion channel， thus proving the pathogenesis of cold and heat of acute coronary syndrome.

In recent years,the isolation rate of carbapenem-resistant Klebsiella pneunoniae(CRKP)in China has increased year by year.Due to its multidrug resistance and high mortality in patients,CRKP brings severe challen-ges to the clinical treatment.The major mechanism of drug resistance in CRKP is the production of carbapenemases,with Ambler A,B,and D being the common types while Ambler type C comparativly rare.Klebsiella pneumoniae carbapenemase(KPC)is the most common carbapenemase,which belongs to type A.KPC-producing Klebsiella pneumoniae(KPC-KP)widely spreads in the world,with very limited number of effective clinical drugs.In this re-view,advances in the treatment KPC-KP were summarized to provide reference for clinical treatment.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

BACKGROUND:The impact of the endometrium's structure and spiral artery blood flow parameters on the pregnancy rate of artificial insemination by husband remains unclear.This study identified the independent factors and constructed a prediction model with good clinical application efficacy after calibration of other confounding factors. OBJECTIVE:To construct and validate a clinical pregnancy prediction model for artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters. METHODS:A retrospective analysis was conducted on 1 299 patients who underwent artificial insemination by husband treatment at Changzhou Maternal and Child Health Hospital from January 2017 to January 2021.The non-pregnancy group consisted of 1 182 patients,while the pregnancy group included 117 patients.Out of these patients,93 cases were successfully matched between the pregnancy and non-pregnancy groups using a 1∶1 propensity score matching method.Single-factor and multi-factor analyses were used to screen the endometrial structure and uterine spiral artery blood flow parameters to determine their influence on artificial insemination by husband outcomes.The optimal cutoff value was established for each independent influencing factor through receiver operating curve analysis and their risk trend affecting artificial insemination by husband pregnancy outcomes was analyzed using a restricted cubic spline.The clinical efficacy of this combined forecast model was tested by using clinical decision curve and clinical influence curve methods. RESULTS AND CONCLUSION:(1)There was no statistical significance in non-endometrial factors between the pregnancy group and the non-pregnancy group,and the data had a good balance by propensity score matching(P>0.05).(2)Single-factor analysis identified several subendometrial parameters as significant influencing factors of artificial insemination by husband pregnancy outcomes,including vascularization index,flow index,vascular flow index,resistance index,pulsatility index,maximum systolic velocity/end-diastolic velocity,thickness of average junction zone and maximum junction zone from the basal endometrium to the outer myometrium inner layer(P<0.05).(3)Multivariate logistic regression analysis revealed that thickness of average junction zone,pulsatility index,and vascular flow index were independent influencing factors of pregnancy outcomes of artificial insemination by husband,vascular flow index>thickness of average junction zone>pulsatility index.(4)Receiver operating characteristic curve analysis indicated that the area under receiver operating characteristic curve of vascular flow index was 0.704(0.629,0.779),and the optimal cutoff value was 6.26;the area under receiver operating characteristic curve of thickness of average junction zone was 0.660(0.582,0.739),and the optimal cutoff value was 6.38;the area under receiver operating characteristic curve of pulsatility index was 0.642(0.563,0.721),and the optimal cutoff value was 1.18.(5)The restricted cubic spline analysis revealed that artificial insemination by husband pregnancy outcomes were significantly positively affected when the vascular flow index was>6.24 or the thickness of average junction zone was≤6.55 mm,while a negative risk was associated with pulsatility index>1.27.(6)The clinical decision curve and clinical influence curve analyses exhibited that the combined prediction model had the maximum clinical net benefit at the threshold probability value of 0.17-0.93,and the ratio of loss to benefit was consistently less than 1 in the threshold probability range,indicating that the model had good clinical efficacy.(7)It is concluded that after adjusting for other confounding factors outside of the endometrium using propensity score matching and multifactorial logistic regression,the thickness of average junction zone,pulsatility index and vascular flow index were independent factors that influenced pregnancy outcomes of artificial insemination by husband.Through determining their optimal cutoff values and assessing their risk trends,it was confirmed that the combined prediction model had good predictive value and clinical efficacy.

ObjectiveTo explore the evolution principles of symptoms including deficiency， phlegm and blood stasis， and of the functional near-infrared spectroscopy （fNIRS） cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease. MethodsA total of 497 patients with complaint of memory loss were included， and were divided into subjective cognitive decline （SCD） group （198 participants）， mild cognitive impairment （MCI） group （228 participants） and dementia （AD） group （71 participants）. Neuropsychological evaluation， traditional Chinese medicine （TCM） syndrome investigation， and fNIRS data collection of prefrontal cortex were performed in each group. Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group； logistic regression was used to analyze the influence of TCM syndromes on the incidence of the patients； association rules were used to analyze the TCM syndromes of the patients； the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared. ResultsKidney essence deficiency syndrome was the dominant syndrome in all stages of AD. There were statistically significant differences in the distribution frequency of kidney essence deficiency， phlegm turbidity obstructing orifices， blood stasis obstructing collaterals， qi and blood deficiency， heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes among the three groups （P＜0.01）， and the scores of kidney essence deficiency syndrome among the three groups were statistically significant （P＜0.01）. Logistic regression analysis showed that kidney essence deficiency， and qi and blood deficiency syndromes were the main risk factors for the SCD group （P＜0.05）， phlegm turbidity obstructing orifices syndrome was the main risk factor for the MCI group （P＜0.05）， and heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group （P＜0.05）. The association rule analysis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support （33.33%） in the SCD group， and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support （32.90% and 52.13%） in both the MCI and AD group. The prefrontal fNIRS results showed that the mean ∆HbO₂ concentration in the left dorsolateral prefrontal cortex （LDLPFC） decreased sequentially among the three groups （P＜0.05）， and the mean ∆HbO₂ concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups （r = -0.142， P＜0.05）. Further analysis showed that the mean ∆HbO₂ concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differences among the three groups （P＜0.05）. ConclusionKidney deficiency is the basis of the pathogenesis of AD， and the key brain area damaged is the LDLPFC. Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease， and the syndromes of AD show the evolution law of deficiency and excess as “kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”. The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms， which can be used to assess the degree of cognitive impairment in AD patients.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.