Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

BACKGROUND:Existing studies have compared patients with degenerative lumbar spondylolisthesis with healthy populations,but comparative studies focusing on differences in this aspect of the parameter between these different lumbar spondylolisthesis are lacking.OBJECTIVE:To explore the differences in paraspinal muscle degeneration between isthmic spondylolisthesis and degenerative lumbar spondylolisthesis,and their correlation with low back pain symptoms.METHODS:A total of 107 patients with lumbar spondylolisthesis treated in Affiliated Hospital of Xuzhou Medical University between February 2019 and August 2023 were analyzed retrospectively.They were divided into the isthmic spondylolisthesis group(39 patients)and the degenerative lumbar spondylolisthesis group(68 patients)according to the type of spondylolisthesis.Paravertebral muscle tissue parameters were compared and analyzed as well as functional scores(visual analog scale for low back pain)in both groups.According to the visual analog scale score,the two groups of patients were divided into two subgroups:those with a visual analog scale score＜45 mm and those with a visual analog scale score＞45 mm,and the relationship between the difference in visual analog scale score and the parameters of paraspinal muscle tissue degeneration was analyzed.RESULTS AND CONCLUSION:(1)The percentage of fat infiltration in the multifidus muscle was higher in the degenerative lumbar spondylolisthesis group than in the isthmic spondylolisthesis group(P=0.003).(2)The percentage of fat infiltration in the multifidus muscle was significantly lower in patients with a visual analog scale score of＜45 mm than in patients with a visual analog scale score of＞45 mm in both groups(P=0.021,P＜0.001).(3)Patients in the isthmic spondylolisthesis group also showed a significantly lower percentage of fat infiltration in patients with visual analog scale score＜45 mm compared with those with visual analog scale score＞45 mm(P=0.002).(4)These results showed that there was a significant difference in paraspinal muscle tissue degeneration between isthmic spondylolisthesis patients and degenerative lumbar spondylolisthesis patients,and that degenerative lumbar spondylolisthesis patients demonstrated more severe paraspinal muscle degeneration compared to isthmic spondylolisthesis patients.In addition,the percentage of fatty infiltration of the multifidus muscle was relatively greater in those with higher pain scores in both groups of lumbar spondylolisthesis patients.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

BACKGROUND:Existing studies have compared patients with degenerative lumbar spondylolisthesis with healthy populations,but comparative studies focusing on differences in this aspect of the parameter between these different lumbar spondylolisthesis are lacking.OBJECTIVE:To explore the differences in paraspinal muscle degeneration between isthmic spondylolisthesis and degenerative lumbar spondylolisthesis,and their correlation with low back pain symptoms.METHODS:A total of 107 patients with lumbar spondylolisthesis treated in Affiliated Hospital of Xuzhou Medical University between February 2019 and August 2023 were analyzed retrospectively.They were divided into the isthmic spondylolisthesis group(39 patients)and the degenerative lumbar spondylolisthesis group(68 patients)according to the type of spondylolisthesis.Paravertebral muscle tissue parameters were compared and analyzed as well as functional scores(visual analog scale for low back pain)in both groups.According to the visual analog scale score,the two groups of patients were divided into two subgroups:those with a visual analog scale score＜45 mm and those with a visual analog scale score＞45 mm,and the relationship between the difference in visual analog scale score and the parameters of paraspinal muscle tissue degeneration was analyzed.RESULTS AND CONCLUSION:(1)The percentage of fat infiltration in the multifidus muscle was higher in the degenerative lumbar spondylolisthesis group than in the isthmic spondylolisthesis group(P=0.003).(2)The percentage of fat infiltration in the multifidus muscle was significantly lower in patients with a visual analog scale score of＜45 mm than in patients with a visual analog scale score of＞45 mm in both groups(P=0.021,P＜0.001).(3)Patients in the isthmic spondylolisthesis group also showed a significantly lower percentage of fat infiltration in patients with visual analog scale score＜45 mm compared with those with visual analog scale score＞45 mm(P=0.002).(4)These results showed that there was a significant difference in paraspinal muscle tissue degeneration between isthmic spondylolisthesis patients and degenerative lumbar spondylolisthesis patients,and that degenerative lumbar spondylolisthesis patients demonstrated more severe paraspinal muscle degeneration compared to isthmic spondylolisthesis patients.In addition,the percentage of fatty infiltration of the multifidus muscle was relatively greater in those with higher pain scores in both groups of lumbar spondylolisthesis patients.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Objective:To investigate the protective effects and mechanism of Shenyan 1 Prescription on renal fibrosis of unilateral ureteral obstruction (UUO) rats through TGF- β 1/Smad homologous 3 (Smad3) pathway regulating ferroptosis.Methods:Totally 48 male SD rats were divided into four groups: sham-operation group, UUO model group, and Shenyan 1 Prescription low-(10 drug/kg) , and high-dosage (20 crude drug/kg) groups according to random number table method, with 12 rats in each group. The UUO model was induced by the method of unilateral ureteral obstruction except for those sham-operation group. After modeling, rats received corresponding drugs or normal saline by gavage for 4 weeks, once per day. After 4 weeks, the body mass and the left kidney weight were measured. The 24 h urine protein and the levels of serum albumin (ALB), alanine aminotransferase (ALT), serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by biochemical analysis method; the ROS level in renal tissue was measured using a chemical fluorescence assay kit, and the SOD and MDA levels in left renal tissue of rats were measured using ELISA method; the morphology of renal tissue and the specific blue staining of hemosiderin were observed using HE and Prussian blue staining methods, respectively; the expressions of transforming growth factor-β1 (TGF-β1), Smad3, glutathione peroxidase 4 (GPX4), and solute carrier family 1 member 5 (SLC1A5) were detected by Western blot.Results:Compared with the model group, the 24 h urinary protein excretion in Shenyan 1 Prescription high-dosage group decreased ( P<0.05), the serum ALB level increased ( P<0.05), the ALT level decreased ( P<0.05), and the expression of SLC1A5 in renal tissue decreased ( P<0.05); the left kidney weight/body decreased in Shenyan 1 Prescription low- and high-dosage groups ( P<0.05); the levels of serum ROS and MDA decreased ( P<0.05), and the activity of SOD significantly increased ( P<0.05); the expressions of TGF-β1 and Smad3 in renal tissue decreased ( P<0.05), and the expression of GPX4 increased ( P<0.05), and the renal pathological injury and ion deposition were improved. Conclusion:Shenyan 1 Prescription has a protective effect on the structure and function of renal tissues in UUO rats through regulating ferroptosis via inhibition of the TGF-β1/ Smad3 pathway to inhibit renal fibrosis of UUO rats.

Objective:To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on the prognosis of critically ill patients with acute gastrointestinal injury (AGI) grade Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of critically ill adult patients with AGI grade Ⅱ, who were enrolled in three randomized controlled trials conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 and May 2019. Data including demographic characteristics, serological indicators of nutrition, the tube tip position confirmed by abdominal X-ray 24 h after tube insertion, and intensive care unit (ICU), 28-day and hospital mortality were collected. Patients were divided into the post-pyloric feeding group and gastric feeding group according to the tube tip position. Propensity score matching method was used to perform 1:1 matching, and the differences of each index between the two groups were compared after matching. Then the influencing factors of P<0.1 were included in multivariate logistic regression analysis to investigate the potential ICU mortality risk factors of critically ill patients with AGI gradeⅡ. Factors with 0.1 level of significance from the univariate analysis were considered in the multivariate analysis. Results:There were 90 patients in post-pyloric feeding group and 90 patients in the gastric feeding group. Demographics and clinical characteristics of study population were well balanced between the two groups after matching. ICU, 28-day and hospital mortality in the post-pyloric feeding group were significantly lower than those in the gastric feeding group (4.4% vs 15.6%, 14.4% vs 27.8%, 6.7% vs 17.8%, all P < 0.05). Multivariate logistic regression analysis indicated that post-pyloric feeding was an independent protective factor [odds ratio ( OR)=0.295, 95% confidence internal (95% CI): 0.091-0.959, P=0.042] and APACHEⅡ score was an independent risk factor ( OR=1.111, 95% CI: 1.025-1.203, P=0.010) for ICU mortality of critically ill patients with AGI gradeⅡ. Conclusions:Post-pyloric feeding for critically ill patients with AGI grade Ⅱ could decrease ICU mortality and is an independent protective factor against mortality.