OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

BACKGROUND:Traumatic brain injury is a condition in which the normal function of the brain is disrupted by a bump or impact to the head.It is necessary to find effective treatments and objective targets that can help doctors diagnose the injury status and restore the brain function of patients. OBJECTIVE:To explore the effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury. METHODS:Forty 6-week-old SPF male Sprague-Dawley rats were randomly divided into five groups:sham group,model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group(electroacupuncture+low-frequency transcranial ultrasound stimulation),with eight rats in each group.Feeney weight-drop method was used to establish the animal model of traumatic brain injury.In the sham group,the bone window was only opened without impact.Interventions were started at 1 day after modeling.Electroacupuncture in the electroacupuncture group,low-frequency transcranial ultrasound stimulation in the low-frequency transcranial ultrasound stimulation group,and electroacupuncture+low-frequency transcranial ultrasound stimulation in the combined group were performed for days in total.The modified neurological severity scale score for assessing rats'neurological deficits was performed at 8 hours after modeling.The percentage of spontaneous alternation behavior in the Y-maze was measured at 7 days after modeling.Then,the electroencephalographic signals were collected and electroencephalographic data of α,β,θ,and δ waves were extracted by fast Fourier transform,and the value of oscillation amplitude and energy ratio were calculated in α,β,θ,and δ waves,as well as the Lempel-Ziv complexity and sample entropy. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological severity scale scores in the model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group were significantly increased at 8 hours after modeling(P<0.05).Compared with the sham group,the value of oscillation amplitude in δ wave and the value of δ energy ratio were significantly increased in the model group at 7 days after modeling,meanwhile the percentage of spontaneous alternation behavior in Y-maze,and the value of α/β energy ratio,Lempel-Ziv complexity,and sample entropy were significantly decreased(P<0.05).Compared with the model group,the value of oscillation amplitude in α and δ waves was significantly decreased in the combined group(P<0.05),while the value of α/β energy ratio was significantly increased(P<0.05)and the value of δ energy ratio was significantly decreased(P<0.05)in the electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group.Compared with the electroacupuncture group and low-frequency transcranial ultrasound stimulation group,the value of δ energy ratio was significantly decreased in the combined group(P<0.05),while the percentage of spontaneous alternation behavior,the value of α/β energy ratio,the Lempel-Ziv complexity,and the sample entropy were significantly increased(P<0.05).To conclude,abnormal electroencephalographic signals can appear in rats with traumatic brain injury,while the electroacupuncture combined with low-frequency transcranial ultrasound stimulation can alleviate the abnormal electroencephalographic signals in rats,which suggests the electroencephalographic frequency domain value and nonlinear features can be used to assess the severity of traumatic brain injury.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

OBJECTIVE To explore the effects of Lycium barbarum polysaccharides on the proliferation， migration， and immune escape of oral cancer cells by regulating the T cell immunoglobulin and mucin domain-containing protein 3 （TIM3）/ galectin-9 （Gal-9） signaling pathway. METHODS Human oral cancer cells KB and CAL27 were assigned to control group， L. barbarum polysaccharides low-concentration group （200 μg/mL）， L. barbarum polysaccharides high-concentration group （400 μg/mL）， pcDNA-NC group （transfection of pcDNA-NC plasmid）， pcDNA-TIM3 group （transfection of pcDNA-TIM3 plasmid）， high concentration of L. barbarum polysaccharides+pcDNA-NC group （400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-NC plasmid）， and high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group （400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-TIM3 plasmid）. The proliferation， migration and invasion abilities of the cells， T cell killing rate as well as the levels of interferon-γ （IFN-γ） and interleukin-2 （IL-2） in the cell supernatant were measured. mRNA expressions of TIM3 and Gal-9 and protein expressions of indoleamine 2，3-dioxygenase 1 （IDO1）， programmed death-ligand 1 （PD-L1）， TIM3 and Gal-9 in the cells were also determined. RESULTS Compared with control group， the clone formation rate， scratch healing rate， the number of invasive cells， protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of L. barbarum polysaccharide low- and high-concentration groups were decreased significantly （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， and the levels of IFN-γ and IL-2 were significantly increased （P＜0.05）. Compared with control group and pcDNA-NC group， the clone formation rate， scratch healing rate， the number of invasive cells， and protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of the pcDNA-TIM3 group were all significantly increased （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， IFN-γ and IL-2 levels were significantly decreased （P＜0.05）. Compared with L. barbarum polysaccharides high-concentration group and high concentration of L. barbarum polysaccharides+pcDNA-NC group， the clone formation rate， scratch healing rate， the number of invasive cells， and protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group were significantly increased （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， and the levels of IFN-γ and IL-2 were significantly decreased （P＜0.05）. CONCLUSIONS L. barbarum polysaccharides may inhibit the proliferation， migration， and immune escape of oral cancer cells by suppressing TIM3/Gal-9 signaling pathway.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Ningxia Hui Autonomous Region from 2014 to 2023, so as to provide the basis for strengthening influenza prevention and control. Methods: Data pertaining to influenza cases reported in Ningxia Hui Autonomous Region from 2014 to 2023 were retrieved from the Infectious Disease Surveillance System of the Chinese Disease Prevention and Control Information System, including age, sex, current residence, onset date, and reporting date. The seasonal incidence of influenza was analyzed using seasonal index. The spatio-temporal clustering characteristics of influenza were identified using spatial autocorrelation analysis and spatio-temporal scan analysis. Results: A total of 20 377 influenza cases were reported in Ningxia Hui Autonomous Region from 2014 to 2023, with a male-to-female ratio of 1.15∶1. The majority were children under 15 years, with 10 950 cases accounting for 53.74%. Influenza was highly prevalent in January, February, March, and December, with seasonal indices of 219.06%, 111.00%, 246.65%, and 366.24%, respectively. The average annual reported incidence was 29.55/100 000, among which Pengyang County, Jinfeng District, Dawukou District, Xiji County, and Litong District had higher average annual reported incidence, at 63.99/100 000, 55.71/100 000, 55.70/100 000, 49.49/100 000, and 49.04/100 000, respectively. Spatial autocorrelation analysis showed that in 2023, there was spatial clustering of influenza cases in Ningxia Hui Autonomous Region (Moran's I=0.333, P<0.05), with a high-high cluster in Jingyuan County, while in other years, the distribution of influenza cases was random (all P>0.05). Spatio-temporal scan analysis showed that from 2014 to 2023, there were four space-time clusters in Ningxia Hui Autonomous Region, including one type Ⅰ cluster in Hongsibao District of Wuzhong City, with the clustering period from January 20 to 26, 2014; and three type Ⅱ clusters, mainly in January, February, March and December, covering one area in Shizuishan City, five areas in Guyuan City, one area in Zhongwei City, three areas in Wuzhong City, and four areas in Yinchuan City. Conclusions From 2014 to 2023, children under 15 years were the primary population affected by influenza in Ningxia Hui Autonomous Region, with distinct spatio-temporal distribution characteristics. The peak incidence occurred during the winter and spring seasons, and the main clustering areas were in the southern regions.

ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

ObjectiveTo investigate the prognostic differences between primary biliary cholangitis （PBC） patients positive for different autoantibodies and the risk factors for poor prognosis， and to facilitate early and effective intervention for PBC patients. MethodsA total of 141 patients who were diagnosed with PBC for the first time in Fenyang Hospital of Shanxi Province from January 2018 to December 2023 were enrolled and divided into group A （80 patients positive for anti-mitochondrial antibody M2 ［AMA-M2］ alone）， group B （36 patients positive for AMA-M2 and anti-gp210 antibody）， and group C （25 patients positive for AMA-M2 and anti-sp100 antibody）， and the three groups were compared in terms of general information， laboratory markers， and prognosis. The Globe score was used for prognostic evaluation， and a Globe score of<0.3 and the absence of liver cirrhosis at the time of confirmed diagnosis were defined as good prognosis， while a Globe score of ≥0.3 or the presence of liver cirrhosis at the time of confirmed diagnosis were defined as poor prognosis. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the prognosis of PBC patients； the receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC） was calculated. ResultsCompared with group A， groups B and C had a significantly higher proportion of male patients， a significantly higher detection rate of liver cirrhosis， significantly higher levels of ALT， TBil， and ALP， and significantly lower levels of PLT and Alb （all P<0.05）. The Globe score was calculated based on related indicators after treatment with ursodeoxycholic acid （UDCA） for 1 year， and the results showed that there was a significant difference in prognosis between the three groups （P<0.001）， and compared with group A， groups B and C had a significantly higher proportion of patients with a Globe score of ≥0.3 （P<0.05） and a significantly higher rate of suboptimal response to UDCA （P<0.05）. The univariate Logistic regression analysis showed that anti-gp210 antibody， anti-sp100 antibody， UDCA response， PLT， Alb， ALT， TBil， and ALP were associated with the prognosis of PBC patients （all P<0.05）. The variables meeting related conditions were included in the multivariate Logistic regression analysis， and the results showed that anti-gp210 antibody （odds ratio ［OR］=4.959， 95% confidence interval ［CI］： 1.112 — 22.122， P=0.036）， anti-sp100 antibody （OR=21.666， 95%CI： 1.542 — 304.449， P=0.023）， Alb （OR=0.899， 95%CI： 0.814 — 0.994， P=0.038）， PLT （OR=0.974， 95%CI： 0.963 — 0.985， P<0.001）， and UDCA response （OR=10.275， 95%CI： 1.047 — 100.831， P=0.046） were independent influencing factors for the prognosis of PBC patients. The ROC curve analysis showed that PLT had the best performance in predicting the prognosis of PBC patients， with an AUC of 0.824， a sensitivity of 85.7%， and a specificity of 71.7%. ConclusionPatients with dual positivity for AMA-M2 and anti-gp210 antibody， as well as those with dual positivity for AMA-M2 and anti-sp100 antibody， tend to have a poorer prognosis and a higher rate of suboptimal response to UDCA. Furthermore， positivity for anti-gp210 antibody， positivity for anti-sp100 antibody， thrombocytopenia， hypoalbuminemia， and suboptimal response to UDCA all indicate poor clinical prognosis.

Objective Under the guidance of meridian-sinew(jingjin)theory,the correlation between foot-yangming jingjin lesions and X-ray imaging findings such as medial space and lateral space in femorotibial joint and their ratio,degree of subluxation of femorotibial joint,and the Insll-Salvati index in the patients with knee osteoarthritis(KOA).Methods From January 2019 to November 2021,a total of 66 patients diagnosed as KOA at the Third Affiliated Hospital of Guangzhou University of Chinese Medicine were selected as the study subjects.The patients were divided into the foot-yangming jingjin group and non-foot-yangming jingjin group according to the presence of foot-yangming jingjin lesions.The X-ray postero-anterior and lateral radiography of the knee joint under weight bearing was performed,and imaging parameters of the two groups were measured.Afterwards the pain Visual Analogue Scale(VAS)scores and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores in the two groups were evaluated,the differences between the two groups'X-ray imaging findings and scale scores were compared,and the various X-ray imaging findings in the two groups were analyzed.Results(1)Under X-ray postero-anterior radiography of the knee joint,the medial space and lateral space in femorotibial joint and their ratio in non-foot-yangming jingjin group were lower than those in foot-yangming jingjin group,and degree of subluxation of femoro-tibial joint was higher than that of foot-yangming jingjin group(P<0.05 or P<0.01).(2)The ratio of length of patellar tendon to length of patella(LT:LP)under X-ray lateral radiography in foot-yangming jingjin group was significantly greater than that of the non-foot-yangming jingjin group(P<0.01).(3)The scores of pain VAS and WOMAC in non-foot-yangming jingjin group were both significantly higher than those in foot-yangming jingjin group(P<0.05),while the differences of the scores of WOMAC items such as joint stiffness and physiologic function,and the total WOMAC scores between the two groups were not statistically significant(P>0.05).Conclusion Foot-yangming jingjin lesions in KOA may be closely related to the relatively high position of patella under X-ray lateral radiography,and non-foot-yangming jingjin lesions may be closely related to the narrowing of the medial femorotibial joint space,the increase of medial-lateral space ratio,and the severity of subluxation under X-ray postero-anterior radiography.

Objective To explore the correlation between the expression of microRNA-452(miR-452)and micro-RNA-221(miR-221)in peripheral blood and post-operative urinary sepsis after percutaneous nephrolithotripsy(PCNL).Methods From January 2019 to June 2023,92 patients with post-operative urinary sepsis after PCNL admitted to 909 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force were regarded as the disease group,92 patients who underwent PCNL surgery during the same period without urinary sepsis were collect-ed as control group.RT-qPCR was applied to detect the expression of miR-452 and miR-221 in peripheral blood;Logistic regression was applied to analyze the influencing factors of urinary sepsis after PCNL surgery;Receiver op-erating characteristic(ROC)curve was applied to evaluate the diagnostic efficacy of peripheral blood miR-452 and miR-221 levels for post-operative urinary sepsis in PCNL patients.Results The time length of the surgical opera-tion in disease group was longer than that in the control group,and the level of miR-452 and miR-221 in peripheral blood,were higher than those in the control group(P＜0.05).Peripheral blood miR-452,miR-221,procalcitonin(PCT),C-reactive protein(CRP),neutrophil to lymphocyte ratio(NLR),urine routine and surgical time were all influence factors for post-operative urinary sepsis in PCNL(P＜0.05).The area under the curve(AUC)for the combined diagnosis of peripheral blood miR-452 and miR-221 in patients with urinary sepsis after PCNL surgery was 0.888,which was better than their individual detection(Zcombination-miR-452=2.005,Zcombination-miR-221=2.972,P=0.045,0.003),the sensitivity and specificity were 77.17%and 91.30%,respectively.Conclusions The change of miR-452 and miR-221 level in peripheral blood is closely related to urinary sepsis after PCNL.Combined testing has a high diagnostic efficacy for post-operative urinary sepsis after PCNL surgery.

OBJECTIVE: To clarify the role of concentrated growth factors (CGF) in the treatment of periodontal cement defects using calcium phosphate cement (CPC) with self-curing properties. METHODS: Thirty-six intrabony defects were randomly divided into two groups. The experimental group received CGF+CPC treatment (n=18), while the control group received CPC treatment alone (n=18). The probing depth, clinical attachment loss, and hard tissue filling as measured by cone beam CT (CBCT) were evaluated at baseline and 1 year postoperatively in both groups, and the levels of major growth factors in CGF and serum were compared [platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF)]. RESULTS: At baseline, there were no statistically significant differences in probing depth, clinical attachment loss and CBCT measurements between the two groups (P>0.05). At 1 year postoperatively, significant improvements were observed in parameters mentioned above in both groups (P < 0.05). The CGF+CPC group seemed more effective compared with the CPC group in reduction of probing depth [(4.5±1.3) mm vs. (3.2±1.1) mm] and clinical attachment gain [(3.8±0.9) mm vs. (2.0±0.5) mm, P < 0.05]. Compared with the group treated with CPC alone, the hard tissue filling degree shown by CBCT in the CGF+CPC group was significantly increased [the reduction of the depth of the intrabony defects was (3.9±1.2) mm vs. (2.1±0.7) mm, respectively, P < 0.01]. At 1 year post-operatively, the volume of the intrabony defects shown by CBCT in the CGF+CPC group was reduced by (0.031 8±0.004 1) mL, which was significantly more than that in the CPC group [(0.019 7±0.001 2) mL, P < 0.05]. In addition, the concentration of the main growth factors (PDGF-BB, TGF-β1, IGF-1, and VEGF) in CGF were higher than those in serum (P < 0.001). CONCLUSION After 1 year of follow-up, the results of the present study indicated that CGF could significantly improve the clinical and radiological effects of CPC on the treatment of periodontal intrabony defects.
Humans ; Calcium Phosphates/therapeutic use* ; Male ; Female ; Bone Cements/therapeutic use* ; Middle Aged ; Cone-Beam Computed Tomography ; Alveolar Bone Loss/therapy* ; Becaplermin ; Adult ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Proto-Oncogene Proteins c-sis/blood* ; Transforming Growth Factor beta1/blood* ; Vascular Endothelial Growth Factor A/blood*