Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ～Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ～Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ～Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ～Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.

Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P＜0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P＜0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ～Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ～Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ～Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ～Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P＜0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P＜0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Objective To construct a perioperative nursing intervention scheme for patients undergoing hepatic arterial infusion chemotherapy(HAIC)via brachial artery access and to discuss its clinical application.Methods By using systematic literature search method,a perioperative nursing intervention scheme was constructed.A total of 90 patients with confirmed hepatic malignancy,who were admitted to hospital to receive HAIC from February 2022 to August 2023,were collected to validate this perioperative nursing intervention scheme,and its clinical application effect was evaluated.Results Through two rounds of expert letter inquiry,a nursing intervention scheme containing five primary indicators and 16 secondary indicators was finally formulated.The clinical validation was conducted.After the implementation of this nursing intervention scheme,the incidences of phlebitis and limb swelling in the intervention group decreased from previous 17.78％ to post-intervention 2.22％ and from previous 33.33％ to post-intervention 8.89％,respectively.The patient's anxiety level and depressed mood were significantly improved;the HADS scores decreased by 35.2％and 36.6％,respectively;the EORTC QLQ-C30 scores in the dimensions of somatic,role,emotional,and social functioning were obviously improved and the quality of life was strikingly improved(all P＜0.05).Besides,in the patients of the intervention group the clinical symptoms(e.g.pain,nausea,etc.)were significant alleviated,and the severity of the symptoms as well as the degree of distress to the patients were significantly reduced,indicating that the nursing intervention plays an important role in relieving the symptoms,anxiety and depression of the patients.Conclusion The perioperative nursing intervention scheme constructed in this study for patients undergoing AIC via brachial artery access is scientific and practical,it provides an important reference basis for the therapeutic nursing care of patients with hepatic malignancy.