Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective To investigate the distribution and evolutionary patterns of traditional Chinese medicine(TCM)syndromes and syndrome elements during the malignant transformation from chronic pancreatitis(CP)to pancreatic intraepithelial neoplasia(Pan IN)and pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was conducted on 710 patients(330 of CP,104 of Pan IN,276 of PDAC)diagnosed pathologically or clinically at Shanxi Institute of Traditional Chinese Medicine from January 2021 to June 2024.Data including demographics,laboratory results,and TCM diagnostic information were recorded using EpiData 3.1.Syndrome and syndrome-element patterns were determined via factor analysis and K-means clustering using SPSS 27.0.Results The study identifies seven TCM syndrome types in CP,Pan IN,and PDAC.Among CP patients,the syndrome distribution was primarily liver-gallbladder damp-heat syndrome(22.42％)and gastrointestinal excess-heat syndrome(20.91％),with excess syndromes accounting for a higher proportion(43.33％);the syndrome elements were mainly heat(51.52％)and dampness(35.15％),with the disease location in the pancreas,related to the liver,spleen,and stomach.In Pan IN patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(23.08％)and liver-gallbladder damp-heat syndrome(17.31％),with mixed deficiency-excess syndrome accounting for a higher proportion(30.00％);the syndrome elements were mainly heat(41.35％),dampness(40.38％),and qi deficiency(37.50％),with the disease location in the pancreas,related to the spleen and liver.In PDAC patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(29.71％)and qi-blood deficiency syndrome(20.29％),with deficiency syndromes accounting for a higher proportion(49.82％);the syndrome elements were mainly qi deficiency(50.00％)and dampness(36.23％),with the disease location in the pancreas,related to the spleen,kidney,and liver.Chi-square tests revealed significant differences in syndrome types(TCM syndromes:x2=100.419,P＜0.001;deficiency-excess syndromes:x2=73.722,P＜0.001),syndrome elements(x2=117.384,P＜0.001),and disease locations(x2=127.191,P＜0.001)across different stages of CP malignant transformation.During CP malignant progression,the proportion of excess syndromes gradually decreased(43.33％→12.32％),while deficiency syndromes increased(26.67％→49.82％).Excess syndrome elements(fire,heat,qi stagnation,blood stasis)decreased(53.48％→25.36％),whereas deficiency syndrome elements(qi deficiency,yin deficiency,yang deficiency,blood deficiency)increased(25.15％→49.64％).The disease location shifted from primarily the liver,spleen,and stomach in the inflammatory stage to the spleen and kidney in the cancerous stage.Conclusion The malignant transformation of CP basically involves the pancreas,is correlated early with liver and spleen-stomach and later with kidney,and exhibits a progression from excess to deficiency in the pattern of"deficiency interweaved with excess syndrome,transition from excess to deficiency,and progressive spleen deficiency".

【Objective】 To discuss the effect of adding tranexamic acid(TXA) during surgery on blood loss and security during short segment lumbar spinal stenosis surgery. 【Methods】 One hundred and eight patients with lumbar spinal stenosis who were to undergo lumbar posterior fusion surgery were randomly divided into control group, TXA group and adding TXA group, with 36 patients in each group. In the control group, TXA was not used during surgery.The TXA group received intravenous infusion of 100 mL normal saline mixture containing 1 g of TXA 15 minutes before surgery after anesthesia. In adding TXA group, after the same operation in TXA group, 10 mg/kg(body weight) of TXA was infused 3 hours later. Total perioperative blood loss, dominant blood loss, hidden blood loss, intraoperative blood loss, postoperative drainage volume, and transfusion rate were recorded in the two groups. Hemoglobin (Hb), hematocrit(HCT), prothrombin time international standardized ratio (PT-INR), prothrombin time(PT), activated partial thromboplastin time(APTT), blood platelet count (BPC), D-dimer (D-D), fibringen(FIB), C-reactive protein (CRP), alanine aminotransferase (ALT), blood urea nitrogen (BUN) were measured 3 days before and after the surgery in the three groups. Postoperative adverse events were followed up. 【Results】 The total blood loss(mL) [(968.7±209.6) vs (1 369.8±276.3), (968.7±209.6) vs (1 273.9±250.2)], dominant blood loss(mL) [(590.5±164.3) vs (876.4±235.9), (590.5±164.3) vs (789.3±221.7)], intraoperative blood loss(mL) [(318.7±120.7) vs (457.8±146.6), (318.7±120.7) vs (423.9±162.3)] and postoperative drainage volume(mL) [1 day after surgery: (164.6±25.0) vs (262.3±51.7), (164.6±25.0) vs (219.8±37.1); 3 days after surgery: (107.2±18.6) vs (156.3±37.6), (107.2±18.6) vs (145.3±22.3)] of the adding TXA group were lower than those of the control group and TXA group (P<0.05), and the transfusion rate was lower than that of the control group (P<0.05).The postoperative drainage volume and transfusion rate of TXA group were lower than that of the control group (P<0.05).There was no statistical difference in the amount of hidden blood loss between the three groups (P>0.05). Compared with the preoperative results, Hb, Hct and BPC in the three groups decreased (P<0.05), and D-D, FIB and CRP increased (P<0.05), but the change degree of Hb, Hct, BPC, D-D and CRP in the TXA group and the adding TXA group was less than that in the control group (P<0.05), and the change degree of Hb, Hct, BPC, D-D and CRP in the adding TXA group was less than that in the TXA group (P<0.05).There was no statistically significant difference in PT-INR, PT, APTT, ALT and BUN between and within the three groups before and after surgery (P>0.05), and all of them were within the normal range. No serious adverse events such as deep vein thrombosis, pulmonary embolism, epilepsy, liver and kidney damage were found in all patients after postoperative follow-up. 【Conclusion】 Intraoperative addition of TXA can effectively reduce the amount of blood lost during short segment lumbar spinal stenosis surgery without increasing the risk of complications such as coagulation disorders, thrombosis, liver and kidney function damage.

OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）. CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.

Objective:To explore the evaluation of dual-parameter three dimension arterial spin labelling(3D-ASL)perfusion imaging on blood-supply situation of patients with chronic middle cerebral artery occlusion(CMCAO)and the relationship between that and cerebral infarction area.Methods:A total of 112 patients with unilateral CMCAO admitted to Handan Central Hospital from April 2019 to December 2021 were selected,and all of them were divided into a compensatory group(50 cases)with anterior cerebral artery(ACA)leptomeningeal anastomoses(LMA)and an uncompensated group(62 cases)according to the results of digital subtraction angiography(DSA)examination.The results of diffusion weighted imaging(DWI),magnetic resonance angiography(MRA)and dual-parameter 3D-ASL detection were respectively analyzed,and the clinical data,3D-ASL parameters and the incidence of cerebral infarction between the two groups were compared.The influence factors of compensation were further analyzed.The receiver operating characteristics(ROC)curve of LMA diagnostic value of CMCAO patients was drawn according to cerebral blood flow values[post label delay(PLD)=1.5 s,2.5 s)].The 3D-ASL parameters of patients with different cerebral infarction areas were compared,and the relationship between 3D-ASL parameters and cerebral infarction area was compared.Results:The apparent diffusion coefficient(ADC)at the side of lesion of CMCAO patients was(0.31±0.10),and cerebral blood flow values at 1.5s and 2.5s were respectively(25.67±4.25)and(54.09±4.49),which were significantly lower than those at the side of healthy,and the differences were statistically significant(t=27.591,34.210,3.913,P<0.05),respectively.The differences of cerebral blood flow values(1.5s and 2.5s)between compensatory group and uncompensated group were significant(t=5.584,4.090,P<0.05),respectively.The results of logistic regression analysis showed that age,stroke,cerebral infarction area and cerebral blood flow values(1.5 s and 2.5 s)were influencing factors on LMA compensation of CMCAO patients(OR=4.187,6.604,0.482,5.681,5.807,P<0.05),respectively.The ROC values showed that the area under curve(AUC)of 3D-ASL were respectively 0.720 and 0.812 in diagnosing LMA when PLD were respectively 1.5s and 2.5s.The proportion of normal and lacunar infarctions in the compensatory group was significantly higher than that in the uncompensated group,while the proportions of middle and small infarction,and large area infarctions of the compensatory group were significantly lower than those of the uncompensated group,and the difference was statistically significant(t=28.062,P<0.05).The difference in cerebral blood flow values(1.5s)among patients with different infarct areas was statistically significant(t=0.202,P<0.05).The cerebral blood flow value(1.5s)of 3D-ASL was negatively correlated with the area of cerebral infarction(r=-0.261,P<0.05).Conclusion:Dual parameter 3D-ASL can non-invasively and visually assess the compensatory status of LMA of patients with unilateral CMCAO.The blood flow perfusion of middle cerebral artery(MCA)at the side of lesion is related to the area of cerebral infarction.When the PLD is 1.5s,the sensitive response can be conducted on this,so as to provide objective and reliable basis for clinical diagnosis and treatment and curative effect.