The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

This study aimed to investigate the effects of acupuncture on dynamic changes in Ca²⁺, Na⁺, and H₂O₂ flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca²⁺ efflux (P < 0.05), extended the period of net Na⁺ influx, and significantly decreased net H₂O₂ efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H₂O₂ efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals ; Muscle, Skeletal/metabolism* ; Rats, Wistar ; Rats ; Male ; Calcium/metabolism* ; Hydrogen Peroxide/metabolism* ; Physical Conditioning, Animal ; Sodium/metabolism* ; Acupuncture Therapy ; NADPH Oxidase 2

OBJECTIVE: To construct an integrated management model for early screening and diagnosis of PCa based on the Innovative Care for Chronic Conditions Framework (ICCC) and the 1+1 contract-based tiered diagnosis and treatment system (TDTS) in China. METHODS: Based on the 1+1 contract-based TDTS platform, we conducted PCa screening for the male residents aged 60 years and above during health check-ups in Pujin Community Health Center from January 1, 2023 to December 31, 2023. For those with abnormal total prostate-specific antigen (tPSA) ≥ 4 μg/L, we promptly referred them to higher-level hospitals for further diagnosis and treatment via the two-way referral green channel platform and information sharing service using the 1+1 contract model. We further analyzed the relevant data on screening and diagnosis. RESULTS: A total of 4 080 males aged 71.39±5.059 years received PCa screening from January to December 2023. PSA screening was performed in 43.96% of the male residents, revealing 654 cases of PSA abnormality, with a PSA positivity rate of 16.03%, which was higher than that found in the previous large-scale PCa screenings in other regions of China. Among the males with PSA abnormality, 292 (44.65%) expressed their willingness for medical referral, while the others did not seek further medical attention for reasons of being asymptomatic, low awareness of the disease, no accompany for medical visits, and concerns about further costs of diagnosis and treatment. Prostate biopsy was recommended to 154 cases after further examinations, which was accepted by 92 (59.74%). Fifty-eight cases were diagnosed with Pa, and thedetection rate reached 63.04%. CONCLUSION The integrated management model for PSA examination-based early screening and diagnosis of PCa using the 1+1 contract-based TDTS platform is plays a significant role in enhancing people's awareness and knowledge of PCa and improving the early detection rate of the malignancy.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Early Detection of Cancer ; Prostate-Specific Antigen/blood* ; Aged ; China ; Mass Screening ; Middle Aged ; Chronic Disease

Objective To prepare glucose transporter 1(Glut1)-targeted doxorubicin(DOX)-loaded liposomes(doxorubicin/polyphyllin H-liposomes,DOX/ppH-LPs)using polyphyllin H(ppH)instead of cholesterol as the liposomal membrane material,and to investigate their in vitro synergistic anti-tumor activity against non-small cell lung cancer(NSCLC).Methods DOX/ppH-LPs were prepared using thin-film hydration,and the formulation was optimized by single-factor investigation.The optimized DOX/ppH-LPs were characterized for morphology,particle size,polydispersity index(PDI),and zeta potential with transmission electron microscopy(TEM)and dynamic light scattering(DLS).Drug loading DL%was determined by high-performance liquid chromatography(HPLC).The storage stability was evaluated by observing in PBS at 4℃for 7 d,and the serum stability was observed in DMEM containing 10%fetal bovine serum(FBS)at 37℃for 48 h.In vitro drug release was studied in PBS at pH 7.4 and pH 5.0 values,respectively.Human NSCLC A549 cells were subjected as the model,MTT assay was performed to detect the proliferation inhibition by DOX/ppH-LPs at different concentrations(0.5,5.0,15.0 μg/mL)and the control group(ppH+DOX/LPs,a physical mixture of free ppH and DOX-loaded liposomes).Fluorescence microscopy was used to observe cellular uptake of DOX/ppH-LPs and DOX/LPs(containing 5 μg/mL DOX)at 15 min and 2 h.Live/dead cell staining was applied to assess apoptosis/necrosis induced by formulations(15 μg/mL DOX)after 48 h incubation.Transwell assay was conducted to evaluate inhibitory effect on cell migration and invasion,and the targeting property and in vitro synergistic anti-NSCLC activity of DOX/ppH-LPs were then comprehensively evaluated.Results The optimal formulation of DOX/ppH-LPs was determined as hydration temperature at 50℃,6 mg DOX,2 mg ppH,and 24 mg lecithin.The prepared DOX/ppH-LPs were in spherical shape,uniform distribution,and at an average particle size of 145.13±22.14 nm,a PDI of 0.15±0.05,a zeta potential of-23.92±1.73 mV,and a DL of 10.13±0.71%for DOX and(1.22±0.21)%for ppH.DOX/ppH-LPs maintained stable particle size,PDI,and exhibited significantly unchanged zeta potential after storage in PBS at 4℃for 7 d or incubation in DMEM containing 10%FBS at 37℃for 48 h,demonstrating excellent physical and serum stability.Both liposomes showed slow release at pH 7.4 value,while drug release was significantly accelerated at pH 5.0 value(P<0.05),indicating pH-sensitive release characteristics.MTT assay revealed that DOX/ppH-LPs exerted significantly stronger cytotoxicity against A549 cells than the ppH+DOX/LPs control group(P<0.05).Compared with ppH+DOX/LPs,DOX/ppH-LPs showed remarkably enhanced cellular uptake in A549 cells(P<0.05),with more DOX localized in the nucleus.Live/dead cell staining showed that at the same DOX concentration(15 μg/mL),the proportion of apoptotic/necrotic cells induced by DOX/ppH-LPs was significantly higher than that of the DOX/LPs control group.Transwell assay demonstrated that there were significantly less cells migrating and invading through the membrane in the DOX/ppH-LPs group than the ppH+DOX/LPs group.Conclusion Glut1-targeted doxorubicin-loaded liposomes(DOX/ppH-LPs)constructed by substituting cholesterol with ppH can target NSCLC cells,significantly enhance the in vitro synergistic anti-NSCLC activity of DOX and ppH.

Objective To explore the clinical effect of active risk prevention nursing on the prevention of skin injury in patients with esophageal cancer during radiotherapy.Methods A total of 102 patients who underwent radiotherapy for esophageal cancer in Jiangsu Cancer Hospital from December 2022 to November 2023 were enrolled.They were assigned to control group(n=51,routine nursing)and study group(n=51,routine nursing+active risk prevention)according to the random number table.The skin injury,quality of life,and nursing satisfaction were compared between the two groups.Results The skin injury in the study group at 20 Gy,40 Gy and at the end of radiotherapy was significantly slighter than that in the control group(P<0.05).After 4 weeks of intervention,the total score of SF-36 and scores in all dimensions in the study group were higher than those in the control group,and the degree of nursing satisfaction in the study group was significantly higher than that in the control group(72.55%vs 94.12%,χ2=8.541,P<0.05).Conclusion Active risk prevention can reduce skin injury,improve quality of life,and help to improve nursing satisfaction in patients with esophageal cancer during radiotherapy.

Objective To investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1(PLK-1)protein.Methods Forty clean grade BALB/c mice,each mouse was implanted with 1×106 CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model.Experimental animals were randomly divided into four groups,the tumor model group(saline control),the positive drug group[oxaliplatin,5 mg/(kg·d)],the low-dose triptolide group[50 μg/(kg·/d)],and the high-dose triptolide group[100 μg/(kg·d)].The drugs were administered through intraperitoneal injection(10 times in total,once every other day).The in vitro effects of the drugs on the proliferation,migration,invasion,and mitosis of CT26 cells were also assessed.Results Triptolide significantly inhibited the proliferation,migration,and invasion of CT26 colon cancer cells,and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells.The binding energy of triptolide and PLK-1 protein was-7.1 kcal/mol,and it could down-regulate the expression of PLK-1 in CT26 cells.Conclusion Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.

Objective The study aims to investigate the impact of microRNA-874-3p(miR-874-3p)regulation of plakophilin 3(PKP3)on the malignant biological behavior of lung adenocarcinoma cells and its underlying mechanism.Methods Immunohistochemistry and immunocytochemistry were used to detect the expression of PKP3 in lung adenocarcinoma tissue microarray and lung adenocarcinoma cell line A549 cells respectively,and the relationship between PKP3 and clinicopathological features of lung adenocarcinoma patients was analyzed.Select lung adenocarcinoma cell line A549,the experiment was divided into A549 cell group(blank control group),miR-NC group(transfected with miR-NC)and miR-mimics group(transfected with miR-874-3p mimics),sh-NC group(control group transfected with PKP3 silencing plasmid),sh-PKP3 group(transfected with PKP3 silencing plasmid),miR+pcDNA-PKP3 group(transfected with miR-874-3P mimics+pcDNA-PKP3,rescue group)and miR+pcDNA-NC group(transfected with miR-874-3p mimics+pcDNA-NC).The proliferation,invasion,migration and apoptosis of cells in each group were detected.ENCORI database was used to predict the upstream gene of PKP3,and dual luciferase assay was used to detect the targeting relationship between miR-874-3p and PKP3.MAPK/mTOR pathway-related proteins were detected by Western blotting.Results The expression of PKP3 in lung adenocarcinoma tissue was significantly higher than that in adjacent tissues.The high expression of PKP3 was related to clinical stage,tumor size,and lymph node metastasis(P＜0.05).Compared with the human normal lung epithelial cells(BEAS-2B),the expression of PKP3 in A549 cells increased significantly,and the expression of miR-874-3p decreased(P＜0.05).Overexpression of miR-874-3p decreased the PKP3 expression level(P＜0.05).Compared with the control group,both overexpression of miR-874-3p and silenced PKP3 inhibited the cloning and invasion ability of A549 cells,caused cell cycle arrest,and decreased the expression levels of cyclin dependent kinase 4(CDK4),cyclin D1,cyclin E1 proteins in A549 cells(P＜0.05).The expressions of Bax protein and Caspase-3 protein were up-regulated(P＜0.05),and apoptosis increased.Overexpression of PKP3 could reverse the biological behavior of overexpression of miR-874-3p.Overexpression of miR-874-3p and silencing of PKP3 significantly decreased the expressions of P38 MAPK and mTOR phosphorylated proteins.Conclusion MiR-874-3p can negatively regulate PKP3 expression and inhibit the malignant biological behavior of A549 cells through MAPK/mTOR pathway.

ObjectiveTo understand the incidence and mortality trends of acute cardiovascular and cerebrovascular events in Yangpu District of Shanghai from 2009 to 2022, and provide a basis for the prevention and control of cardiovascular and cerebrovascular events. MethodsData were obtained from the Shanghai Acute Cardiovascular and Cerebrovascular Events Surveillance Platform. Data on the incidence and mortality of cardiovascular and cerebrovascular events in the population (age group, gender) from 2009 to 2022 were collected, and the Joinpoint Regression Program version 4.9 was used to calculate the average annual percent change (AAPC) in the incidence and mortality rates of acute cardiovascular and cerebrovascular events. ResultsFrom 2009 to 2022, the crude incidence and standardized incidence rate of acute cardiovascular and cerebrovascular events in Yangpu District showed no significant changes (AAPC=1.41%, P=0.569; AAPC=-1.03%, P=0.675), the crude mortality rate of acute cardiovascular and cerebrovascular events in Yangpu District did not change significantly (AAPC=-3.04%, P=0.213), while the standardized mortality rate showed a decreasing trend (AAPC=-6.23% P=0.014). From 2009 to 2022, the crude incidence rates and age-standardized incidence rates for both males and females in Yangpu District showed no significant changes. The crude mortality trends for both genders were not significant, while the age-standardized mortality rates showed a decline (AAPC=-5.33%, P=0.029; AAPC=-7.50%, P=0.006). The incidence rate and age-standardized incidence rate were higher in males than in females. The crude incidence rates in the 30‒, 40‒, and 45‒year-old age groups increased annually (AAPC=9.13%、7.11%、4.67%, all P=0.001), and the crude mortality ratse in the 60‒, 65‒, 70‒, 75‒, 80‒, and 85‒year-old age groups declined annually (AAPC=-4.24%, P=0.044; AAPC=-5.41%, P=0.028; AAPC=-6.73%, P=0.004; AAPC=-7.46%, P=0.002; AAPC=-8.24%, P=0.002; AAPC=-6.16%, P=0.035). ConclusionFrom 2009 to 2022, the crude incidence, standardized incidence rate and crude mortality rate of cardiovascular and cerebrovascular events in Yangpu District tended to be stable, and the standardized mortality rate showed a downward trend. Men, middle-aged and young people were the key groups in the prevention and treatment of cardiovascular and cerebrovascular diseases, and it should be continued to improve the ability of medical emergency and increase the integration of medical and prevention.