Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective Evaluation of the efficacy of high-frequency repetitive transcranial magnetic stimulation for chronic disturbance of consciousness after severe craniocerebral injury based on magnetic resonance spectroscopy.Methods The clinical data of 106 patients with chronic disturbance of consciousness after severe craniocerebral injury from January 2018 to December 2022 were retrospectively analyzed,and they were divided into control group(conventional rehabilitation treatment)and observation group(high frequency repetitive transcranial magnetic stimulation treatment)by propensity score matching method(1∶1),with 53 cases in each group.Both groups were examined by magnetic resonance spectroscopy(MRS)before and after treatment.The brain metabolic indexes[N-acetyl aspartate(NAA)/creatine(Cr)value,choline complex(Cho)/Cr value],Glasgow coma scale(GCS)score,electroencephalogram(EEG)grading,coma recovery scale(CRS-R)score,brainstem auditory evoked potential(BAEP)grading,upper limb sensory evoked potential(SSEP)grading and Cerebral blood flow perfusion index[cerebral blood volume(CBV),mean transit time(MTT),cerebral blood flow(CBF)]were compared between the two groups.Results After treatment,the NAA/Cr values of the thalamus and brainstem in the two groups increased,while the Cho/Cr values decreased,and the levels of brain metabolic indexes in the observation group were signifi-cantly better than those in the control group(P<0.05).The two groups'GCS score and CRS-R score increased,and the improvement of the observation group was better than that of the control group(P<0.05).The BAEP grading,EEG grading,and SSEP grading of the two groups improved,and those of the observation group were better than the control group(P<0.05).The CBF and CBV of the two groups increased,and MTT decreased,and the level of cere-bral blood perfusion index in the observation group was better than that in the control group(P<0.05).Conclusion High frequency repetitive transcranial magnetic stimulation has a significant effect on the recovery of patients with chronic consciousness disorders after severe craniocerebral injury.The mechanism may be related to improving the blood flow velocity of brain tissue and metabolism in the brain.

Objective To screen the specific cytokines of tuberculous pleural effusion(plTB)by using liquid array technique to establish a diagnostic model and discuss its application value.Methods A total of 86 patients with plTB(plTB group)were included,including 41 patients in the confirmed plTB group and 45 patients in the clinically diagnosed plTB group.There were 42 other patients with pleural effusion in the control group.Seventeen cytokines in pleural effusion were analyzed by liquid array technology.Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-9,IL-10,gamma-interferon-induced protein 10(IP-10),IL-15,IL-17F,IL-27,tumor necrosis factor(TNF)-α,monocyte chemotactic protein-1(MCP-1),the expression levels of macrophage inflammatory protein-3a(MIP-3α),macrophage colony-stimulating factor(M-CSF)and β-interferon(IFN-β)were detected.Difference factors between the confirmed plTB group and the control group were screened,and the receiver operating characteristic(ROC)curve was drawn in the confirmed plTB patients.IP-10,IL-27 and MCP-1 with AUC>0.850 and specificity>80%were combined to diagnose plTB,and were compared with adenylate deaminase(ADA)and T-SPOT.TB in pleural effusion to evaluate the diagnostic efficacy.Results The levels of IL-2,IP-10,IL-27,TNF-α and MCP-1 were higher in the confirmed plTB group than those in the control group(P＜0.05).The sensitivity and specificity of IP-10,IL-27 and MCP-1 in the diagnosis of plTB were 87.8%and 81.0%.The sensitivity of three-factor combined diagnosis in 45 patients with plTB was still as high as 86.7%,and there was no significant difference in sensitivity compared with that in the diagnosed plTB group(P＞0.05).In the plTB group,the sensitivity of IP-10,IL-27 and MCP-1 combined detection was 87.2%,which was higher than that of T-SPOT.TB(81.4%)and ADA(54.7%).Conclusion The application of liquid array technology to the joint detection of pleural effusion IP-10,IL-27 and MCP-1 can provide help for the diagnosis of plTB.

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary society.Addressing these concerns is an imperative task,with the aims of postponing the aging process and finding effective treatments for age-related degenerative diseases.Recent investigations have highlighted the significant roles of nicotinamide adenine dinucleotide(NAD+)in the realm of anti-aging.It has been empirically evidenced that supplementation with nicotinamide mononucleotide(NMN)can elevate NAD+levels in the body,thereby ameliorating certain age-related degenerative diseases.The principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism,inhibition of cell apoptosis,modulation of immune function,and preservation of genomic stability,which collectively contribute to the deferral of the aging process.This paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN,elucidates the inherent limitations of current research,and proposes novel avenues for anti-aging investigations.

Objective To develop a nurse-patient interaction integrated APP"NET Home"to provide detailed care and follow-up management for patients with neuroendocrine tumors(NENs)trea-ted with long-acting octreotide.Methods"NET Home"APP included three ports:patient side,medical side and management side.After discharge,NENs patients timely and comprehensive fed back on adverse reactions and discomfort symptoms through APP,and medical staff timely guided patients to deal with them online.Results At 1 year after"NET Home"APP application,45 patients registered(injected with long-acting octreotide once every 28 days).A total of 145 copies of Micro-nutrition Evaluation Scales,147 Tumor Patients'Quality of Life Rating scales,102 Pain Digital Evaluation Scales,103 Adverse Reactions Questionnaire of Long-acting Octreotide Injection,102 Self-care Ability Scales,111 Self-rating Scales for depression and 102 Self-rating Scales for anxiety were collected.The medical staff treated 5 cases of adverse reactions by APP,and gave timely handling to 1 case of severe adverse reactions(the patient eventually stopped long-acting octreotide therapy).Compared with NENs patients who did not use APP,anxiety scores of NENs patients who used APP decreased(P＜0.05);their satisfaction scores and quality of life scores were improved,and the number of unplanned admissions decreased,but the differences showed no statistically significant(P＞0.05).Conclusion"NET Home"APP can realize refined and personalized nursing intervention through multiple module functions,which can realize continuous home care for NENs patients,relieve their anxiety and improve their self-management ability,quality of life and treatment compliance.

Objective To develop a nurse-patient interaction integrated APP"NET Home"to provide detailed care and follow-up management for patients with neuroendocrine tumors(NENs)trea-ted with long-acting octreotide.Methods"NET Home"APP included three ports:patient side,medical side and management side.After discharge,NENs patients timely and comprehensive fed back on adverse reactions and discomfort symptoms through APP,and medical staff timely guided patients to deal with them online.Results At 1 year after"NET Home"APP application,45 patients registered(injected with long-acting octreotide once every 28 days).A total of 145 copies of Micro-nutrition Evaluation Scales,147 Tumor Patients'Quality of Life Rating scales,102 Pain Digital Evaluation Scales,103 Adverse Reactions Questionnaire of Long-acting Octreotide Injection,102 Self-care Ability Scales,111 Self-rating Scales for depression and 102 Self-rating Scales for anxiety were collected.The medical staff treated 5 cases of adverse reactions by APP,and gave timely handling to 1 case of severe adverse reactions(the patient eventually stopped long-acting octreotide therapy).Compared with NENs patients who did not use APP,anxiety scores of NENs patients who used APP decreased(P＜0.05);their satisfaction scores and quality of life scores were improved,and the number of unplanned admissions decreased,but the differences showed no statistically significant(P＞0.05).Conclusion"NET Home"APP can realize refined and personalized nursing intervention through multiple module functions,which can realize continuous home care for NENs patients,relieve their anxiety and improve their self-management ability,quality of life and treatment compliance.

Objective:To evaluate the role of mitophagy in cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 13-14 weeks, weighing 230-250 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), SAE group and SAE+ autophagy inhibitor 3-methyladenine (3-MA) group (3-MA group).The SAE models were developed by cecal ligation and puncture in anesthetized animals.3-MA 10 mg/kg was intraperitoneally injected at 30 min after developing the model in 3-MA group.Cognitive function was assessed by Morris water maze test, and the escape latency and ratio of the time of staying at the target quadrant were recorded.After the end of Morris water maze test, the rats were sacrificed and hippocampal tissues were collected for microscopic examination of the pathological changes which were scored after hematoxylin-eosin staining and for determination of the expression of autophagy-related proteins LC3, Beclin1 and p62 (by Western blot).The ratio of LC3Ⅱ/LC3Ⅰwas calculated.The hippocampal mitochondria were isolated to measure mitochondrial membrane potential (MMP), ATP content and ATPase activity by spectrophotometry. Results:Compared with Sham group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, and the contents of MMP and ATP and ATPase activity were decreased in SAE and 3-MA groups, the ratio of LC3Ⅱ/LC3Ⅰwas significantly increased, the expression of Beclin1 was up-regulated, and the expression of p62 was down-regulated in SAE group, and the ratio of LC3Ⅱ/LC3Ⅰwas significantly decreased, and the expression of Beclin1 and p62 was up-regulated in 3-MA group ( P<0.05).Compared with SAE group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, the ratio of LC3/LC3Ⅰwas decreased, the expression of Beclin1 was down-regulated, the expression of p62 was up-regulated, and the contents of MMP and ATP and ATPase activity were decreased in 3-MA group ( P<0.05). Conclusions:Hippocampal mitophagy is involved in cognitive dysfunction in the rats with SAE.

Objective:To explore the application value of the family-centered nursing model and home care platform in PICC nursing of elderly tumor patients, in order to provide reference for PICC nursing of elderly tumor patients.Methods:A total of 122 elderly tumor patients admitted to Boao Hengda International Hospital, Hainan Province from October 2017 to October 2019 were selected and divided into control group (61 cases) and observation group (61 cases) according to the random number table method. The control group received routine care. The observation group combined family-centered care with home care platform for nursing intervention. Before and 3 months after intervention, the self-management ability, quality of life and mental resilience of the two groups were evaluated by Cancer Patients PICC Self-Management scale(CPPMS), 36-item Short Form Health Survey(SF-36) and Connor-Davidson Resilience Scale(CD-RISC). The incidence of complications during the observation period and service volume was recorded.Results:There was no significant difference in the score of CPPMS,SF-36, CD-RISC before intervention between the two groups( P>0.05). The CPPSM scores of the observation group and the control group after intervention were (144.21±8.93) points and (125.85±10.52) points, the difference was statistically significant ( t value was 10.392, P<0.05). The scores of social function, life vitality, physical pain, physical function, physical role limitation, emotional role limitation, mental health and overall health were (70.34±5.96),(68.27±5.01),(63.46±4.57),(58.53±5.78),(59.74±6.49),(60.32±5.69),(59.83±6.72),(66.58±6.76) points in the observation group, and (65.32±6.04), (65.33±6.57), (58.35±4.92), (54.51±4.82), (55.64±6.12), (54.59±6.42), (55.67±5.06), (62.14±4.77) points in the control group, the differences were statistically significant ( t values were 2.779-5.943, P<0.05). The CD-RISC scores of the observation group and the control group after intervention were (82.41±8.79) points and (73.39±7.64) points, the difference was statistically significant ( t value was 6.049, P<0.05). There was no significant difference in the complication rate between the two groups ( P>0.05). The number of calls, consultations, and door-to-door services were (6.77±1.27), (6.34±1.92), (2.58±0.52) times/person in the observation group, and (4.52± 1.48), (4.06±1.41), (2.03±0.19) times/person in the control group, the difference was statistically significant( t values were 9.011, 7.475, 7.759, P<0.05). Conclusions:Compared with conventional care, the family-centered care model and home care platform have higher application value in elderly patients with PICC oncology, which can effectively improve the PICC management ability and quality of life of patients, and further improve the psychological flexibility. It is worthy of promotion and application.

Objective:To evaluate the role of p38 mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy (SAE).Methods:Sixty healthy male C57BL6 mice, weighing 24-27 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sep), tetramethylpyrazine group (group TMP) and p38 MAPK inhibitor SB203580 group (group SB). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally once a day at 3 days before the establishment of the model in TMP group, and SB203580 2.0 mg/kg was intraperitoneally injected at 30 min after the establishment of the model in SB group.The equal volume of normal saline was given intraperitoneally in Sham and Sep groups.At 1 day after operation, cognitive function was assessed by Morris water maze, and the escape latency and ratio of time spent in the target quadrant were recorded.The animals were sacrificed after the test, and hippocampal tissues were taken for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylation of p38 MAPK, GSK3 and CREB and expression of brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the contents of IL-1β, TNF-α and IL-6 were increased, the phosphorylation of hippocampus p38 MAPK was increased, the phosphorylation of GSK3 and CREB were decreased, and the expression of BDNF was down-regulated in Sep, TMP and SB groups ( P<0.05). Compared with group Sep, the escape latency was significantly shortened, the ratios of time spent in the target quadrant were increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the phosphorylation of hippocampus p38 MAPK was decreased, the phosphorylation of GSK3 and CREB were increased, and the expression of BDNF was up-regulated in TMP and SB groups ( P<0.05). Compared with group TMP, no significant change was found in the parameters mentioned above in group SB ( P>0.05). Conclusion:p38 MAPK/CREB signaling pathway is involved in the process of tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with SAE.

Objective:To observe the characteristics of the phagocytosis and bactericidal function of multidrug-resistant Mycobacterium tuberculosis(MDR- Mtb)-infected macrophage model, and the changes of the immune response and metabolic function in the process of phagocytosis and bactericidal function, aiming to provide reference for studying the role and mechanism of macrophages in the occurrence and development of multidrug-resistant tuberculosis(MDR-TB). Methods:We established MDR- Mtb and H37Rv-infected macrophage models, and used the colony-forming unit (CFU), Magnetic Luminex ? Assay and Cholesterol Assay kit to observe the effects on phagocytosis and bactericidal function, the secretion of Th1(IL-12/23 p40, IL-27 and TNF-α) and Th2 cytokines (IL-6 and IL-10) and cholesterol metabolism. The data were analyzed by SPSS25.0 software. The data were expressed as Mean± SD and analyzed by t test or F test. P<0.05 was considered statistically significant. Results:(1) After MDR- Mtb-infected macrophages, the intracellular CFU gradually increased and reached the highest at 24 h, while the extracellular CFU gradually decreased and reached the lowest at 24 h. The intracellular CFU at 48 h was lower than that at 24 h, while the extracellular CFU was higher than that at 24 h ( P<0.05). Both intracellular and extracellular CFU at 48 h were close to those at 4 h ( P>0.05). The intracellular CFU was lower than the H37Rv group at 8-48 h, while the extracellular CFU was higher than the H37Rv group ( P<0.05). (2) The level of IL-12/23 p40, IL-27, TNF-α, IL-6 and IL-10 of MDR-TB group were higher than those of blank group ( P<0.05), but the level of TNF-α and IL-6 at 24 h and 48 h were higher than that at 4 h ( P<0.05). IL-12/23 p40 and TNF-α at 48 h and IL-6 at 24 h were lower than those of the H37Rv group, while IL-27 at 48 h was higher than that of the H37Rv group ( P<0.05). (3) The levels of cholesterol of MDR-TB group at 24 h and 48 h were lower than those of 4 h and blank group ( P<0.05), but the level of cholesterol was similar to the H37Rv group at any time ( P>0.05). (4) TNF-α reached the highest when the intracellular CFU reached the highest at 24 h, and IL-6 reached the highest when the intracellular CFU decreased at 48 h. With the decreasing of cholesterol expression, the intracellular CFU increased and then decreased. Conclusions:MDR- Mtb could induce the phagocytosis and bactericidal function of macrophages, increase the expression of Th1 and Th2 cytokines and promote the utilization and consumption of cholesterol, but this function was weaker than that of H37Rv strain.