With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

OBJECTIVE: To construct the inflammation score (IS) and nutrition-immunity score (NIS) for patients with multiple myeloma (MM), and to verify their prognostic stratification effects and significance. METHODS: The clinical data of 129 newly diagnosed MM patients admitted to our hospital from August 2011 to September 2022 were retrospectively analyzed. Univariate and multivariate Cox regression analysis of overall survival (OS) were comducted on clinical parameters, including inflammatory indicators such as red blood cell volume distribution width (RDW) and platelet count (PLT), nutritional-immune indicators such as albumin (ALB), absolute lymphocyte count (ALC), and suppressed immunoglobulin count (S-Ig count). To construct IS and NIS for prognosis, X-tile software and multivariate Cox regression analysis were used to verify the prognostic stratification role and significance of IS and NIS. The time-dependent receiver operating characteristic (ROC) curve, C-index curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical net benefit of IS and NIS in predicting overall survival(OS), and compared to the international staging system (ISS). RESULTS: IS was constructed based on the scores of RDW and PLT, and NIS was constructed based on the scores of ALB, ALC, and S-Ig count. According to X-tile analysis and multivariate Cox regression analysis, IS and NIS can divide the patients into three risk strata respectively: low, medium and high IS and NIS groups. The differences in OS and hazard ratio (HR) between the low, medium, and high strata were statistically significant (P < 0.05). IS and NIS are both independent prognostic predictors for MM. The area under the ROC curve (AUC) and C index of IS and NIS for predicting 1- to 7-year OS were greater than those of ISS, and both were greater than 0.7. The prediction results of IS and NIS for 1-, 3-, and 5-year OS rates were well consistent with the actual observed results. The DCA curves of IS and NIS for predicting 1-, 3-, and 5-year OS were higher than that of ISS in a wide range of threshold probability intervals. CONCLUSION IS and NIS have independent predictive significance for OS in MM patients. Their predictive discrimination, accuracy, and clinical net benefit are higher and better than ISS, and they may have potential application value in MM prognosis.
Humans ; Multiple Myeloma/immunology* ; Prognosis ; Retrospective Studies ; Inflammation ; Male ; Female ; Middle Aged ; ROC Curve ; Aged ; Nutritional Status ; Proportional Hazards Models

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Objective To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum.Methods A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template.In 3D-printing group,there were 14 patients,includ-ing 10 males and 4 females;aged from 21 to 53 years old;CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted.In conventional group,there were 15 patients,including 10 males and 5 females;aged from 19 to 55 years old;conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted.Blood loss,surgical time,radiographic quality of reduction,and hip function were compared between groups.Results The difference in operation time and intraoperative blood loss was significant(P＜0.05).Twenty-three patients were followed up from 12 to 30 months,and the fractures in both groups healed with a healing time of 3 to 6 months.At the last follow-up,the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conven-tional group(P＜0.05),with no significant differences in walking ability,hip mobility and total score(P＞0.05).In 3D printing group,6 cases were excellent,5 cases were good,3 cases were fair;in conventional group,5 cases were excellent,5 cases were good,4 cases were fair,1 case was worse;no significant difference between two groups(P＞0.05).Conclusion Virtual preopera-tive planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery,im-prove the quality of reduction.This method is efficient,accurate and reliable to treat acetabular posterior wall fractures.

Objective:To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation,the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated.Methods:Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023,42 cases among which were included in the infection-positive group,and 30 cases in the suspected infection group.Forty-two donors un-vaccinated against SARS-CoV-2,un-infected,and donated three consecutive apheresis platelets from October to November 2022 were included in the control group.The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before(Time1)and after(Time2 and Time3)the onset of symptoms,three consecutive times(Time1,Time2,Time3)in the control group by repeated measures analysis of variance.The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.Results:Simple effect of the number times of tests in the positive and suspected infection groups was significant(Finfection-positive group=6.98,P＜0.001,partial η2=0.79,Fsuspected infection group=4.31,P＜0.001,partial η2=0.70).The positive group and the suspected infection group had lower RBC,HCT,and HGB,and higher PLT and PCT at Time2 compared to Time1 and Time3(P＜0.05).The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2(P＜0.001).The simple effect of the number times of tests in the control group was not significant(F=0.96,P=0.55,partial η2=0.34).The difference of the whole blood count parameters in the control group for three times was not statistically significant(P＞0.05).We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.The equation had an eigenvalue of 0.22,a canonical correlation of 0.43(x2=27.81,P＜0.001),and an analysis accuracy of 72.9％.Conclusion:The hematological indicators of RBC,HCT,HGB,PLT,PCT,RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes.The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.