This paper systematically reviews the current status of integrated traditional Chinese and western medicine in the treatment of Helicobacter pylori （Hp） infection， as well as recent progress in clinical and basic research both in China and internationally. It summarizes the advantages of traditional Chinese medicine （TCM） in Hp infection management， including improving Hp eradication rates， enhancing antibiotic sensitivity， reducing antimicrobial resistance， decreasing drug-related adverse effects， and ameliorating gastric mucosal lesions. These advantages are particularly evident in patients who are intolerant to bismuth-containing regimens， those with refractory Hp infection， and individuals with precancerous gastric lesions. An integrated， whole-process management approach and individualized， staged comprehensive treatment strategies combining TCM and western medicine are proposed for Hp infection. Future prevention and control of Hp infection should adopt an integrative Chinese-western medical strategy， emphasizing prevention， strengthening primary care， implementing proactive long-term monitoring， optimizing screening strategies， and advancing the development of novel technologies and mechanistic studies of Chinese herbal interventions. These efforts aim to provide a theoretical basis and practical pathways for the establishment and improvement of Hp infection prevention and control systems.

This article summarizes professor WEI Zixiao's clinical experience in the differentiation and treatment of diabetes mellitus complicated with urinary tract infection from the perspective of taiyin （太阴） and shaoyin （少阴）. Professor WEI takes taiyin and shaoyin in the six meridians as the core differentiation framework， and puts forward that the core pathogenesis lies in deficiency of both the spleen and kidney， and the dysfunction of qi transformation as the root， and damp-heat pouring downward as the branch. It is held that xiaoke （wasting-thirst， 消渴） and strangury originate from the same pathogenesis yet present distinct clinical manifestations. Chronic cases are mostly characterized by deficiency-excess complex， lingering and difficult to heal. In clinical practice， the disease is condensed into four syndromes， taiyin syndrome， shaoyin cold-transformation syndrome， shaoyin heat-transformation syndrome， and concurrent taiyin and shaoyin syndrome. The key therapeutic principle is to restore the transportation function of the taiyin （spleen） and to enhance the qi-transformation function of the shaoyin. The corresponding methods include tonifying the middle and replenishing qi， warming the kidney and transforming qi， nourishing yin and relieving strangury， as well as strengthening healthy qi and relieving strangury. Representative formulas include Buzhong Yiqi Decoction （补中益气汤）， Jisheng Shenqi Pill （济生肾气丸）， Zhibai Dihuang Pill （知柏地黄丸） combined with Zhuling Decoction （猪苓汤）， and Buzhong Yiqi Decoction combined with Jisheng Shenqi Pill， all with appropriate modifications. Bitter-cold medicinals are used cautiously， with emphasis on strengthening healthy qi and addressing both the root and the branch.

ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

Objective: To study the correlation between activated partial thromboplastin time (APTT) mixing test results and the inhibitor titers in hemophilia A inhibitor-positive patients. Methods: In this cross-sectional study, 41 patients with severe hemophilia A and inhibitors (and negative for lupus anticoagulant) were included from the hemophilia clinic of Shandong Blood Center from February 2022 to February 2024. All patients underwent APTT mixing test. The Rosner's index (RI, including the immediate RI and the RI after 2-hour water bath incubation [water bath 2h RI]), the time-dependent difference (Δ value), and the corrected percentage were calculated based on results of APTT mixing test. The median (interquartile range) of the corresponding indexes were calculated, and the ROC curves for identification of high inhibitor titers using the four indexes (the immediate RI, the water bath 2h RI, the Δ value, and the corrected percentage) were plotted, The correlations between APTT mixing test and inhibitor titers for coagulation factor Ⅷ (Factor Ⅷ, FⅧ) were investigated. Results: The median (lower quartile, upper quartile) of immediate RI, water bath 2h RI, Δ-value and corrected percentage for FⅧ inhibitor positive patients were 11.0 (5.4, 29.3)%, 45.0 (25.7, 75.0)%, 26.2 (7.6, 41.8) s, and 82.2 (58.5, 91.6)%, respectively. The median (lower quartile, upper quartile) of the immediate RI, water bath 2h RI, Δ-value and corrected percentage were 25.2 (13.0, 37.5)%, 64.1 (44.6, 72.6)%, 38.0 (14.3, 38.3) s, and 66.5 (50.1, 82.1)% for the high-titer inhibitor group, and 5.2 (4.2, 9.4)%, 17.9 (8.8, 28.0)%, 13.0 (7.6, 25.4) s, and 92.3 (88.0, 94.3)% for the low-titer inhibitor group. The AUCs of the ROC curves for discrimination between high and low titer inhibitor were: 0.9105 for immediate RI, 0.9118 for water bath 2h RI, 0.8873 for correcter percentage, and 0.6532 for Δ-value. Conclusion: High-titer inhibitors can be highly suspected in hemophiliac patients with an immediate RI >10% and a water bath 2h RI >45%, and the presence of low-titer inhibitors is suspected in patients with a 4-second < immediate RI <10% and a 13% < water bath 2h RI <45%.

This paper primarily investigated the protective effects and potential mechanisms of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma in alleviating isoprenaline(ISO)-induced hypertrophy and damage in H9c2 cardiomyocytes. Initially, H9c2 cardiomyocytes were used as the research subject to analyze the effects of ISO at different concentrations on cell hypertrophy and damage. On this basis, the H9c2 cardiomyocytes were divided into blank, model, and high-dose(200 μg·mL~(-1)), medium-dose(100 μg·mL~(-1)), and low-dose(50 μg·mL~(-1)) groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma. Cell hypertrophy and damage models were induced by treating cells with 400 μmol·L~(-1) ISO for 24 hours. The Incucyte live-cell analysis system was utilized to observe the status, size changes, and confluence of the cells in each group. Cell viability was detected by using the CCK-8 assay. Western blot analysis was employed to detect the expression of Ras-associated protein 7A(RAB7A), sequestosome 1(SQSTM1/p62), autophagy-related protein Beclin1, and microtubule-associated protein 1 light chain 3(LC3). Immunofluorescence was used to detect the expression level of the autophagy marker Beclin1 in H9c2 cells. The results demonstrated that compared with the blank group, the model group showed a significant reduction in cell viability(P<0.01) and a marked increase in cell hypertrophy, with an average cell length growth of 13.53%. Compared with the model group, the high-dose, medium-dose, and low-dose groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma exhibited reduced hypertrophy, with respective growths of 6.89%, 8.30%, and 8.49% and a significant decrease in growth rates(P<0.01). Cell viability in the high-dose of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma was also significantly increased(P<0.01). Western blot and immunofluorescence results indicated that compared with the blank group, the model group showed changes in Beclin1, RAB7A, and p62 expression, as well as the LC3Ⅱ/LC3Ⅰ ratio, although most changes were not statistically significant. In the groups treated with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma, the expression of autophagy-related proteins Beclin1 and RAB7A and the LC3Ⅱ/LC3Ⅰ ratio were significantly increased(P<0.05), while p62 expression significantly decreased(P<0.05). These findings collectively suggested that pretreatment of cells with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma significantly enhanced autophagy activity in cells. In summary, total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma inhibit ISO-induced hypertrophy and damage in H9c2 cells by promoting autophagy, demonstrating potential cardioprotective effects and providing new insights and scientific evidence for their preventive and therapeutic use in cardiovascular diseases.
Autophagy/drug effects* ; Saponins/pharmacology* ; Panax notoginseng/chemistry* ; Panax/chemistry* ; Animals ; Rats ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Rhizome/chemistry* ; Isoproterenol/adverse effects* ; Myocytes, Cardiac/cytology* ; Hypertrophy/drug therapy*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objectives:To investigate the effect of interferon-γ(IFN-γ)on the repair of dental pulp injury.Methods:hDPSCs were isolated and cultured,and the hDPSCs were divided into control group,0.05 ng/mL IFN-γ group,0.5 ng/mL IFN-γ group,5 ng/mL IFN-γ group and 0.5 ng/mL IFN-γ+PDTC group.Transwell was used to detect the effect of IFN-γ on the migration abil-ity of human dental pulp stem cells,alizarin red staining was used to evaluated the influence of IFN-γ on the osteogenic differentia-tion of hDPSCs,and the expression of protein related to Wnt/β-catenin signaling pathway in cells was detected by Western blot.The rat dental pulp mechanical injury model was established,and the 3D cultured hDPSCs cell mass and hDPSCs cell mass with 0.5 ng/mL IFN-γ were placed in the cavity of the established rat dental pulp injury model.The cavity was filled with glass ionomer,and HE staining was used to compare the repair of dental pulp tissue in each group of rats.Results:The number of migrating cells in dif-ferent concentrations of IFN-γ groups was significantly higher than that in the control group,and the difference was statistically signif-icant(P＜0.05),and the number of migrated cells in the 0.5 ng/mL IFN-γ group was more than that in the 0.05 ng/mL IFN-γgroup and the 5 ng/mL IFN-γ group(P＜0.05).Compared with the control group,the mineralized nodules and osteoblastic differ entiation of hDPSCs in different concentrations IFN-γgroups were significantly inhibited(P＜0.05).Compared with the 0.5 ng/mL IFN-γ group,the mineralized nodule formation and osteogenic differentiation of hDPSCs in the 0.5 ng/mL IFN-γ+PDTC group were enhanced(P＜0.05).Compared with the control group,the ALP activity of IFN-γ group and IFN-γ+PDTC group was significantly lower(P＜0.05),and the ALP activity of IFN-γ+PDTC group was higher than that of IFN-γgroup,and the difference between groups was statistically significant(P＜0.05).Compared with the control group,the protein ex-pression levels of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ group and IFN-γ+PDTC group were significantly decreased,while the GSK-3β and p-GSK-3β had increased,and the difference between the groups was statistically significant(P＜0.05),the protein expressions of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ+PDTC group were significantly higher than those in the IFN-γ group,while the protein expression levels of p-GSK-3β and GSK-3β were lower than those in the IFN-γ group,and the differences between the groups were statistically significant(P＜0.05).Compared with the control group,the inflammatory response in the dental pulp mechanical injury model of the IFN-γ group was aggravated,and the dentin formation was significantly inhibited.Conclusion:IFN-γ can promote the migration of hDPSCs and inhibit the osteogenic differentiation of hDP-SCs,and IFN-γ has an inhibitory effect on the formation of restorative dentin after pulp injury,which may be related to the expres-sion regulation of Wnt signaling pathway.

Objectives:To investigate the effect of interferon-γ(IFN-γ)on the repair of dental pulp injury.Methods:hDPSCs were isolated and cultured,and the hDPSCs were divided into control group,0.05 ng/mL IFN-γ group,0.5 ng/mL IFN-γ group,5 ng/mL IFN-γ group and 0.5 ng/mL IFN-γ+PDTC group.Transwell was used to detect the effect of IFN-γ on the migration abil-ity of human dental pulp stem cells,alizarin red staining was used to evaluated the influence of IFN-γ on the osteogenic differentia-tion of hDPSCs,and the expression of protein related to Wnt/β-catenin signaling pathway in cells was detected by Western blot.The rat dental pulp mechanical injury model was established,and the 3D cultured hDPSCs cell mass and hDPSCs cell mass with 0.5 ng/mL IFN-γ were placed in the cavity of the established rat dental pulp injury model.The cavity was filled with glass ionomer,and HE staining was used to compare the repair of dental pulp tissue in each group of rats.Results:The number of migrating cells in dif-ferent concentrations of IFN-γ groups was significantly higher than that in the control group,and the difference was statistically signif-icant(P＜0.05),and the number of migrated cells in the 0.5 ng/mL IFN-γ group was more than that in the 0.05 ng/mL IFN-γgroup and the 5 ng/mL IFN-γ group(P＜0.05).Compared with the control group,the mineralized nodules and osteoblastic differ entiation of hDPSCs in different concentrations IFN-γgroups were significantly inhibited(P＜0.05).Compared with the 0.5 ng/mL IFN-γ group,the mineralized nodule formation and osteogenic differentiation of hDPSCs in the 0.5 ng/mL IFN-γ+PDTC group were enhanced(P＜0.05).Compared with the control group,the ALP activity of IFN-γ group and IFN-γ+PDTC group was significantly lower(P＜0.05),and the ALP activity of IFN-γ+PDTC group was higher than that of IFN-γgroup,and the difference between groups was statistically significant(P＜0.05).Compared with the control group,the protein ex-pression levels of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ group and IFN-γ+PDTC group were significantly decreased,while the GSK-3β and p-GSK-3β had increased,and the difference between the groups was statistically significant(P＜0.05),the protein expressions of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ+PDTC group were significantly higher than those in the IFN-γ group,while the protein expression levels of p-GSK-3β and GSK-3β were lower than those in the IFN-γ group,and the differences between the groups were statistically significant(P＜0.05).Compared with the control group,the inflammatory response in the dental pulp mechanical injury model of the IFN-γ group was aggravated,and the dentin formation was significantly inhibited.Conclusion:IFN-γ can promote the migration of hDPSCs and inhibit the osteogenic differentiation of hDP-SCs,and IFN-γ has an inhibitory effect on the formation of restorative dentin after pulp injury,which may be related to the expres-sion regulation of Wnt signaling pathway.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.