Objective:Effects of Qingsui Xiaoyan Decoction on osteoclast differentiation of RAW264.7 cells.Methods:Receptor activator of nuclear factor kappa B ligand (RANKL) was used to induce differentiation of RAW264.7 cells into osteoclasts. CCK-8 method was used to screen experimental drug concentrations and analyze the cytotoxicity of drug intervention on RAW264.7 cells. TRAP staining method was used to quantitatively detect the effects of Qingsui Xiaoyan Decoction on osteoclast differentiation ability. RT-PCR technology was used to detect the mRNA expressions of osteoclast differentiation genes TRAP, MMP-9, CK, CTR. Western blot was used to detect osteoclast-related protein expressions of NF-κBP65, IκB-αTRAP, and TRAP.Results:After 72 hours of intervention, 0.800, 4.000, 20.000, and 100.000 mg/ml of Qingsui Xiaoyan Decoction could inhibit cell proliferation ( P<0.05). Compared with the model group, the number of TRAP-positive cells decreased ( P<0.05) in the 5, 20, 80, and 160 μg/ml Qingsui Xiaoyan Decoction groups. Additionally, the mRNA levels of TRAP, MMP-9, CK, and CTR decreased ( P<0.05), the expression of NF-κB p65 and TRAP proteins decreased ( P<0.05), and the expression of IκB-α protein increased ( P<0.05). Conclusions:Qingsui Xiaoyan Decoction can inhibit the expressions of TRAP, MMP-9, CK, CTR genes and TRAP protein, reduce the degradation of I κ B - α protein by inhibiting the NF - κ B signaling pathway, inhibit the expression of NF - κ B p65 protein, and thus inhibit the differentiation of RAW264.7 into osteoclasts.

OBJECTIVE To evaluate the efficacy and safety of high-dose ilaprazole combined with amoxicillin for newly diagnosed elderly patients with Helicobacter pylori （Hp） infection， and analyze independent risk factors for failure of Hp infection eradication treatment. METHODS Totally 200 cases of newly diagnosed elderly patients with Hp infection in Xinxiang Central Hospital from August 1， 2021 to December 1， 2024 were selected and randomly divided into control group and study group， with 100 cases in each group. The control group was treated with classic quadruple therapy regimen （Amoxicillin capsules+ Clarithromycin tablets+Bismuth potassium citrate tablets+Ilaprazole enteric-coated tablets）. The study group was treated with high- dose Ilaprazole enteric-coated tablets+Amoxicillin capsules. All patients were administered medication for 2 weeks. Hp eradication rates in the two groups were compared using intention-to-treat （ITT） and per-protocol （PP） analyses. The incidence of adverse reactions in both groups was also recorded. The multiple-factor Logistic regression analysis was used to identify independent risk factors for failure of Hp infection eradication treatment. RESULTS In ITT and PP analyses， there was no significant difference of Hp eradication rates between the two groups （P＞0.05）. There was no significant difference in incidence of mild to moderate adverse reactions between the two groups （P＞0.05）. BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease were identified as independent risk factors influencing the failure of Hp infection eradication treatment （P＜0.05）. CONCLUSIONS The efficacy and safety of high-dose ilaprazole combined with amoxicillin are comparable to classic quadruple therapy regimen in treating newly diagnosed elderly patients with Hp infection. Independent risk factors influencing the failure of Hp infection eradication treatment include BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To study the changes of serum metabolites in the patients with chronic kidney disease osteoporosis(CKD-OP)to provide the new biomarkers for the early diagnosis of CKD-OP.Methods A total of 22 patients with definitely diagnosed CKD visiting in this hospital from April to Novem-ber 2023 were selected as the study subjects,and 22 subjects with physical examination in this hospital at the same period were included for conducting the control study.With the lumbar vertebral T value ≤-2.5 as the standard,the subjects were divided into the CKD-OP group(n=11),CKD non-OP group(CKD-NOP group,n=11),simple osteoporosis group(OP group,n=11)and healthy control group(NC group,n=11).The liq-uid chromatography-mass spectrometry(LC-MS)coupling technique was used to analyze the differences in se-rum metabolites among the four groups,the potential biomarkers of CKD-OP was screened,and the correla-tion between the potential biomarkers with lumbar vertebra bone mineral density(BMD),serum bone-derived alkaline phosphatase(BALP)and serum tartrate-resistant acid phosphatase-5b(TRACP-5b)was studied.Re-sults With the receiver's operating characteristic(ROC)curve's area under curve(AUC)＞0.9 as the con-dition,and four potential biomarkers of CKD-OP were screened,which were phosphorylcholine,lysophosphati-dylcholine(18∶2/0∶0),capric acid,and allantoin respectively.Serum phosphorylcholine was positively corre-lated with lumbar vertebra BMD(r=0.601,P＜0.05)and negatively correlated with serum BALP and TRACP-5b(r=-0.729,-0.623,P＜0.05).Serum allantoin was positively correlated with lumbar vertebra BMD(r=0.483,P＜0.05)and negatively correlated with serum BALB(r=-0.494,P＜0.05).Serum lyso-phosphatidylcholine(18∶2/0∶0)was positively correlated with lumbar vertebra BMD(r=0.640,P＜0.05),and negatively correlated with serum BALP and TRACP-5b(r=-0.628,-0.548,P＜0.05).Serum capric acid was negatively correlated with lumbar vertebra BMD(r=-0.444,P＜0.05)and positively corre-lated with serum BALB(r=0.587,P＜0.05).Conclusion The screened four endogenous potential biomarkers provide the new research ideas for the early diagnosis and treatment efficacy monitoring of CKD-OP.

This paper summarized the key points and methods in terms of the establishment of the guideline working group and the management of conflict of interests， trying to provide reference for the development of clinical practice guidelines for Chinese patent medicine （CPM）. The establishment of the working group is the first important step for developing CPM guidelines. Considering the characteristics of the clinical practice guidelines for CPM， this study suggests that the three key elements of ‘multidisciplinarity’， ‘clinical relevance’ and ‘geographical representativeness’ should be put focus on when forming the working group. The guideline advisory committee， clinical expert group， evidence systematic evaluation group， secretary group and the external review group should be established. All group members should clarify the conflict of interest， and the process and management method of the conflict of interest should be clearly reported.

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Objective To investigate the regulatory mechanism of Rehmanniae Radix Praeparata and its active components rehmannioside D and catalpol on γ-aminobutyric acid(GABA)in the brain based on the xylosy-transferase I(xylt-1)signaling pathway.Methods(1)SD rats were randomly divided into normal group,model group and treatment group(Rehmanniae Radix Praeparata group,30 g·kg-1),with eight rats in each group,half male and half female.The rat model of yin deficiency was established by intragastric administration of traditional Chinese medicine compound(30 g·kg-1)with acrid-warm nature and dampness-drying and dampness-draining,once in the morning and once in the evening,for 10 consecutive days.After modeling,the treatment group was given Rehmanniae Radix Praeparata decoction by gavage,once in the morning and once in the evening,for 10 consecutive days.The body mass of rats was measured and recorded,and the activity,crossing times and total distance were detected by open field behavior experiment.The levels of serum gonadotropin-releasing hormone(GnRH),thyrotropin-releasing hormone(TRH),corticotropin-releasing hormone(CRH),luteinizing hormone(LH)and follicle-stimulating hormone(FSH)in rats were detected by ELISA.The mRNA and protein expression levels of xylt-1,multiligand proteoglycan 1(SDC-1),early growth response factor 1(EGR1)and glutamate decarboxylase 1(GAD67)in rat brain tissue were detected by qPCR and automatic capillary Western Blot.The content of GABA in brain tissue was detected by HPLC.(2)The xylt-1 gene of rat well-differentiated adrenal pheochromocytoma cells(PC12)was silenced by siRNA.The cells were divided into normal group,negative control group,silencing group,silencing+rehmannioside D(10 μmol·L-1)group,silencing+catalpol(10 μmol·L-1)group.The expression levels of xylt-1,SDC-1,EGR1 and GAD67 mRNA in cells were detected by qPCR.The content of GABA in intracellular and extracellular fluid was detected by HPLC.The expression level of SDC-1 in cells was detected by immunofluorescence.(3)PC12 cells were transfected with lentivirus to overexpress xylt-1 gene.The cells were divided into normal group,negative control group(empty vector group)and overexpression group.The mRNA expression levels of xylt-1,SDC-1,EGR1 and GAD67 in cells were detected by qPCR.Results(1)Compared with the normal group,the body mass of the rats in the model group was significantly decreased(P＜0.01),the activity was significantly increased(P＜0.01),and the number of crossings and the total distance were significantly increased(P＜0.01).The levels of serum LH,FSH,GnRH,CRH and TRH were significantly increased(P＜0.01).The content of GABA in hippocampus and cerebral cortex was significantly decreased(P＜0.05,P＜0.01).The expression of xylt-1,SDC-1,EGR1 and GAD67 mRNA(hippocampus,cerebral cortex)and protein(hypothalamus,cerebral cortex)in brain tissue were significantly down-regulated(P＜0.05,P＜0.01).Compared with the model group,the body mass of the rats in the treatment group was significantly increased(P＜0.05),the activity was significantly decreased(P＜0.01),and the total distance was significantly shortened(P＜0.05).The levels of serum LH,FSH,GnRH,CRH and TRH were significantly decreased(P＜0.01).The content of GABA in hippocampus and cerebral cortex was significantly increased(P＜0.05,P＜0.01).The content of GABA in hippocampus and cerebral cortex was significantly increased(P＜0.05,P＜0.01).The expressions of xylt-1,SDC-1,EGR1 and GAD67 mRNA(hippocampus,cerebral cortex)and protein(hypothalamus,cerebral cortex)in brain tissue were significantly up-regulated(P＜0.05,P＜0.01).(2)Compared with the negative control group,the mRNA expressions of xylt-1,SDC-1,EGR1 and GAD67 in the silencing group was significantly down-regulated(P＜0.01).The content of GABA in intracellular and extracellular fluid was significantly decreased(P＜0.05,P＜0.01).The expression of SDC-1 in cells was significantly down-regulated(P＜0.01).Compared with the silencing group,the expression of xylt-1 mRNA in the silencing+rehmannioside D group was up-regulated,but the difference was not statistically significant(P＞0.05).The mRNA expression of xylt-1 in the silencing+catalpol group was significantly up-regulated(P＜0.05).The mRNA expressions of SDC-1,EGR1 and GAD67 in the silencing+rehmannioside D group and the silencing+catalpol group was significantly up-regulated(P＜0.05,P＜0.01),the content of GABA in the intracellular and extracellular fluid was significantly increased(P＜0.01),and the expression of SDC-1 in the cells was significantly up-regulated(P＜0.05,P＜0.01).(3)Compared with the normal group and the negative control group,the mRNA expression of xylt-1 in the overexpression group was significantly up-regulated(P＜0.01).Compared with the negative control group,the mRNA expressions of SDC-1,EGR1 and GAD67 in the overexpression group was significantly up-regulated(P＜0.01),and the GABA content in the intracellular and extracellular fluid was significantly increased(P＜0.01).Conclusion There may be a xylt-1/SDC-1/EGR1/GAD67 pathway that regulates GABA synthesis in the brain.Rehmanniae Radix Praeparata may increase GABA levels in the brain by up-regulating this pathway.