The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Objective To analyze the caregiver presence needs and their influencing factors among hospitalized elderly non-surgical patients and provide a basis for formulating relevant policies.Methods A descriptive qualitative study method was adopted.Through purposive sampling,semi-structured interviews were conducted on elderly non-surgical patients and their families and medical staff in Peking Union Medical College Hospital from September to October 2023.MAXQDA 2020 and the 7-step phenomenological analysis method of Colaizzi were used to classify and code the interview contents and identify themes.Results The categories of caregiver presence needs of elderly non-surgical patients included basic living assistance needs,disease monitoring needs,psychological support needs,as well as the needs for family members to provide economic support and participate in treatment decision-making.The influencing factors included advanced age,frailty,the lack of self-care ability in patients with comorbidities,the susceptibility of patients to sudden situations during the disease exacerbation period,the increased risk of unexpected events in patients with psychological distress,and patients' concerns about social support and medical decision-making.Conclusion The caregiver presence needs of elderly non-surgical patients during hospitalization are high and influenced by multiple factors.
Humans ; Caregivers/psychology* ; Aged ; Hospitalization ; Social Support ; Male ; Qualitative Research ; Female

Objective To explore the validity and feasibility of the left transthoracic and esophageal hiatal approach for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction under a single position.Methods The clinical data of 64 patients with Siewert type Ⅱ AEG(single position transthoracic approach group)treated with the left transthoracic and esophageal hiatal approach under a single position and 56 patients with the laparoscopic transesophageal slit approach(transabdominal approach group)in the Department of Thoracic Surgery,Huaihe Hospital of Henan University,from January 2017 to December 2018 were retrospectively analyzed.The clinical and pathological data,perioperative indicators(operation time,intraoperative blood loss,postoperative first ambulation time,postoperative first peristalsis time,postoperative drainage volume at 3 d,incidence of postoperative complications,postoperative hospital stay),postoperative complications(positive surgical margin,proximal esophageal resection margin,tumor diameter,total number of dissected lymph nodes,positive lymph node dissection rate,postoperative histopathology,and TNM staging of tumor pathology),and survival indicators(tumor recurrence and metastasis rate and survival at 1 month,3 months,6 months,1 year,3 years,5 years after surgery)were compared between the two groups.Kaplan-Meier method was used to analyze the postoperative survival rate of the two groups.Univariate analysis using χ2 test was employed to analyze factors influencing 5-year postoperative survival rate in Siewert type Ⅱ AEG patients.Results No significant difference was observed in clinical and pathological data,such as gender,age,American Society of Anesthesiologists(ASA)grade,tumor differentiation,pTNM stage,and tumor diameter between the two groups(P>0.05).No significant differences were noted in intraoperative blood loss,incidence of postoperative complications,and survival rates at 1 month,3 months,6 months,1 year,and 3 years after surgery between the two groups(P>0.05).The single position transthoracic approach group exhibited a higher postoperative drainage volume at 3 d compared to the transabdominal approach group(P<0.001),a shorter surgical time(P<0.001),a longer time to first mobilization,first intestinal peristalsis,and hospital stay after surgery(P<0.01),a longer proximal esophageal margin(P<0.001),a higher total number of lymph node dissections(P<0.001),and a higher positive lymph node dissection rate(P<0.05)than the transabdominal approach group.The 5-year recurrence-free survival rate of the single position transthoracic approach group was higher than that of the transabdominal approach group,with a statistically significant difference(P=0.013).The Kaplan-Meier survival curve showed no statistically significant difference in the 5-year overall survival rate between the two groups of patients after surgery(P=0.456).The results of univariate analysis indicated that there are significant relationships between tumor differentiation degree,pTNM stage,tumor diameter,and lymph node positivity rate with the 5-year postoperative survival rate in Siewert type Ⅱ AEG patients(P<0.05).Conclusion Siewert type Ⅱ AEG patients can be treated with the left transthoracic and esophageal hiatal approach under a single position,achieving the same effect as laparoscopic transesophageal slit approach,and it can be actively promoted as a complementary choice of operation in the clinic.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.

Objective:To integrate and analyze the trend of the disease burden of tracheal,bronchus,and lung cancer(TBL)attributable to secondhand smoke in China from 1990 to 2021 and to analyze future projections,aiming to provide data support for the prevention and treatment of TBL in China.Methods:Based on the global burden of disease(GBD)2021 database,TBL with ICD-10 disease classification C33,C34-C34.92 was studied.Using secondhand smoke as a risk factor,the data on TBL mortality and disability-adjusted life year(DALY)due to secondhand smoke in China from 1990 to 2021 were further age-standardized.Using Joinpoint 4.7.1 regression analysis model to calculate annual percentage change(APC)and average annual percentage change(AAPC),Hiplot software was used to plot disease burden data for different ages and genders,and R 4.3.1 software was used to construct a grey model GM(1,1)to predict the predicted value and trend of TBL disease burden attributed to secondhand smoke in China from 2022 to 2031.Results:From 1990 to 2021,the TBL mortality rate,age-standardized mortality rate,and DALY rate attributed to secondhand smoke in China increased from 1.76/100 000,2.63/100 000,and 49.43/100 000 to 4.08/100 000,2.80/100 000,and 95.57/100 000,respectively;the growth was 131.18%,6.45%,and 93.34%;the age-standardized DALY rate decreased from 65.04/100 000 to 63.32/100 000 with the reduction of 2.65%.The results of the Joinpoint regres-sion showed that the AAPC(95%CI)of mortality,age-standardized mortality rate,and DALY rate for TBL were 2.75(2.58-2.93)%,0.16(0.11-0.21)%,and 2.15(2.11-2.18)%,respectively,with an overall increasing trend;the AAPC(95%CI)of age-standardized DALY rate was-0.14(-0.40-0.12)%,with an overall fluctuating and unchanged trend and it was higher in males than in females.In both 1990 and 2021,the TBL mortality rate attributable to secondhand smoke in China gradually increased with age,and the DALY rate first increased and then slowed down with age.The main groups of the burden of disease were the elderly and males.The grey prediction model GM(1,1)showed that the age-standardized mortality rate of TBL attributable to secondhand smoke from 2022 to 2031 showed a slow increasing trend,and the predicted value in 2031 would increase to 2.95/100 000.The age-standardized DALY showed a slow decreasing trend,and the predicted value in 2031 would decrease to 63.83/100 000.Conclusions:From 1990 to 2021,the TBL mortality,age-standardized mortality,and DALY rates attributable to secondhand smoke in China increased,and the age-standardized DALY rate decreased.Men and the elderly are the main groups affected by TBL.Appropriate measures should be formulated to reduce exposure to and contact with secondhand smoke,tak-ing into account gender and age differences.Additionally,efforts should be made to strengthen secondhand smoke prevention and public health education.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.

Objective:To screen inflammatory markers that can be used for the diagnosis and intervention evaluation of patients with chronic kidney disease(CKD)with depression,and to systematically study the therapeutic effect and safety of modified Chaihu Longgu Muli decoction in patients with CKD with depression.Methods:This study was a prospective study,a total of 120 patients with CKD who were diagnosed and treated in the Department of Nephrology,Chongqing Traditional Chinese Medicine Hospital from April 2023 to October 2024 were included.They were divided into CKD with depression(CKD-D)group and CKD without depression(CKD-N)group according to the diagnostic criteria by random number table method.The results of routine laboratory tests were collected,and the severity of depressive disorder was evaluated by Hamilton Depression Rating Scale-17(HAMD-17).The levels of interleukin-18(IL-18),interferon-γ(IFN-γ),β-thromboglobulin(β-TG),platlet factor-4(PF-4),eosinophil chemotactic factor(Eotaxin),soluble tumor necrosis factor receptor-2(sTNFR-2)and CD40 ligand(CD40L)in serum were quantitatively evaluated by liquid chip technology.Pearson correlation analysis was used to analyze the correlation between HAMD-17 scores and inflammatory markers with statistical differences in CKD patients with depression at different stages.The patients in CKD-D group were randomly divided into control group and treatment group.The control group was given basic treatment of CKD,while the treatment group was treated with modified Chaihu Longgu Muli decoction on the basis of the control group.After 8 weeks of continuous intervention,the clinical effective rate,the changes of effective inflammatory markers and the occurrence of adverse reactions were compared between the two groups.Results:In the CKD-D group and the CKD-N group,the difference of HAMD-17 score,serum phosphorus(P),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),albumin(ALB),serum iron(Fe3+),C-reactive protein(CRP),IL-18,IFN-γ,sTNFR-2 indicators were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that in addition to HAMD-17 score(OR=1.259,P=0.006),SCr(OR=1.748,P=0.003),eGFR(OR=1.354,P=0.005),serum IL-18(OR=0.924,P=0.011)and IFN-γ(OR=0.859,P=0.031)levels were also independent influencing factors for CKD patients with depression.Pearson correlation analysis showed that there was a significant positive correlation between HAMD-17 score and IL-18,IFN-γ,sTNFR-2 and CD40L.The total clinical effective rate of the treatment group was higher than that of the control group,and the serum levels of IL-18 and IFN-γ in the treatment group were lower than those in the control group,the differences were statistically significant(P＜0.05),and no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:IL-18 and IFN-γ can be used as effective serum markers for the diagnosis and treatment of depressive disorders in CKD patients.At the same time,the changes of serum levels of IL-18 and IFN-γ can be used to evaluate the severity of symptoms in CKD patients with depression at different stages to a certain extent.Modified Chaihu Longgu Muli decoction may improve CKD combined with depressive symptoms and improve the quality of life of patients by down-regulating the level of inflammatory factors.

OBJECTIVE: To investigate the clinical efficacy and safety of single Kirschner wire assisted poking and closed reduction in the treatment of Gartland type Ⅲ supracondylar humeral fractures in children. METHODS: A retrospective analysis was performed on patients diagnosed with Gravland type Ⅲ supracondylar humeral fractures between January 2022 and June 2023. A total of 46 patients were treated with closed reduction assisted by Kirschner wires and percutaneous Kirschner wire internal fixation.There were 25 males and 21 females. The age ranged from 5 to 10 years old, with an average of (5.8±1.8) years old. The left side was involved in 28 patients and the right side in 18 patients. Record the operative duration for patients, the number of fluoroscopic exposures, fracture healing time, postoperative carrying angle, Baumann angle, elbow joint function score at three months post-operation, and any associated complications. RESULTS: All 46 patients were followed up for a period of 12 to 16 weeks, with an average of (13.74±1.44 )weeks. The operation duration was (30.7±5.1) minutes, the fluoroscopy count was (10.2±2.7) times, the postoperative carrying angle of the elbow joint was (8.7±2.2) degrees, and the Baumann angle was (71.5±2.9) degrees. All fractures achieved successful union in all patients, with a mean healing time of (25.5±1.7) days.At the final follow-up, elbow joint function was assessed using the Flynn criteria, with 43 patients rated as excellent and 3 patients rated as good. No complications were observed, including cubitus varus, nerve injury, or local infection. CONCLUSION The use of a single Kirschner wire assisted prying reduction for treating Gartland type Ⅲ supracondylar humeral fractures in children demonstrates excellent clinical efficacy and safety.
Humans ; Male ; Female ; Child ; Bone Wires ; Child, Preschool ; Humeral Fractures/physiopathology* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Fracture Healing

OBJECTIVE: To compare the clinical efficacy of unilateral biportal endoscopic discectomy(UBE) and percutaneous interlaminar endoscopic discectomy(PIED) in the treatment of highly migrated lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on 43 patients with highly migrated LDH who underwent spinal endoscopic surgery between January 2022 and December 2023. In the UBE group 22 patients included 8 males and 14 females, aged 49 to 59 years old with a mean of (54.13±2.07) years old. In the PIED group 21 patients included 11 males and 10 females, aged 49 to 59 years old with a mean of (55.04±2.80) years old. Perioperative parameters including intraoperative blood loss, operative time, and fluoroscopic exposures were compared between groups. Clinical outcomes were assessed using the visual analogue scale (VAS) for pain, Oswestry disability index (ODI), and modified MacNab criteria. Complications during the perioperative period and follow-up were recorded. RESULTS: In the PIED group, there were 3 cases of nerve injury, 1 case of residual nucleus pulposus, and 1 case of dural injury. In the UBE group, there was 1 case of nerve injury and 1 case of cerebrospinal fluid leakage. No infections or major bleeding occurred in either group. All patients completed surgery and were followed up for at least 12 months. The UBE group had significantly more intraoperative blood loss (39.09±6.10) ml and more fluoroscopic exposures (6.45±0.26) than the PIED group (34.05±5.62) ml and (3.24±0.28) with significant difference (P<0.05). Preoperative VAS and ODI showed no significant differences between two groups (P>0.05). Both groups demonstrated significant improvements in VAS and ODI postoperatively (P<0.001). At the 3rd days postoperatively, the UBE group had a significantly lower leg pain VAS (2.27±0.20) than the PIED gruop(2.95±0.24) with significant difference (P<0.05), but no significant differences were observed at the first or 12th months (P>0.05). No significant differences in ODI were found between two groups during follow-up (P>0.05). At the 1st month postoperatively, according to modified MacNab criteria, 15 patients got excellent results, 4 good, and 2 fair in PIED group;and 18 patients got excellent results, 2 good, and 2 fair in UBE group, with no significant difference between two groups(P>0.05). CONCLUSION Both PIED and UBE are effective surgical methods for treating highly migrated LDH. Compared with PIED, UBE involves slightly longer operative time, more blood loss, and more fluoroscopic exposures, but carries a lower risk of nerve injury.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/surgery* ; Endoscopy/methods* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Diskectomy, Percutaneous/methods* ; Treatment Outcome