BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

OBJECTIVE: To explore the application effectiveness of multidisciplinary team (MDT) in the diagnosis and treatment of chronic refractory wounds, and to provide new ideas for optimizing the clinical diagnosis and treatment of such diseases. METHODS: A retrospective analysis was performed on the clinical data of patients with chronic refractory wounds who underwent surgery at Peking University Third Hospital from January 2015 to October 2023, and a total of 456 patients, including 290 males and 166 females, with an average age of (49.4±16.9) years. According to whether preoperative MDT discussion was conducted, the patients were divided into MDT discussion group and non-MDT discussion group. The overall implementation process of MDT included: Starting and recording with the medical office, collecting data and discussing the initial MDT, informing the patient of the treatment plan and strictly implementing it, and the change of the condition needs to be discussed again by MDT. The general clinical data, anesthesia risk grade, complications (hypertension, diabetes, coronary heart disease), and the etiology and location of chronic refractory wounds between the two groups were compared. The main observational measurements and outcome indicators of treatment effectiveness included the number of surgeries required to achieve wound healing after admission, the recurrence rate after wound healing, the incidence of perioperative complications (pulmonary infection, severe cardiovascular event, vein thrombus embo-lism, cerebral stroke and delirium, etc.), and patient satisfaction score. RESULTS: There were 189 patients in the MDT discussion group and 267 patients in the non-MDT discussion group. There was no significant statistical difference in the clinical data, such as age, gender, body mass index, American Society of Anesthesiologists, comorbidities, etiology, and location of chronic refractory wounds between the two groups (P>0.05). The average number of surgeries required for wound healing in MDT discussion group and non-MDT discussion group was 2.1±1.1 and 2.8±1.6, respectively, with a statistically significant difference (P < 0.001). This difference was also significant in chronic refractory wounds caused by three etiologies: Diabetic ulcer, infection after trauma or surgery, and non-union after radiotherapy (P < 0.05). The recurrence rate of the patients in the non-MDT discussion group after wound healing was 18.0%, slightly higher than that in the MDT discussion group of 14.3% (P>0.05). In terms of perioperative complications, the non-MDT discussion group also had a higher incidence (3.7% vs. 2.6%), but the difference was not statistically significant (P>0.05). In terms of patient satisfaction, the MDT discussion group scored significantly higher (96.5 vs. 91.1, P=0.028). CONCLUSION The MDT mode can significantly reduce the number of surgeries for patients with chronic refractory wounds, improve the effectiveness of therapy and increase patient satisfaction. It is a recommended model for optimizing the clinical diagnosis and treatment effectiveness of chronic refractory wounds.
Humans ; Patient Care Team ; Retrospective Studies ; Chronic Disease ; Male ; Female ; Middle Aged ; Wound Healing ; Aged ; Adult ; Wounds and Injuries/surgery*

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To observe the protective effect and possible mechanism of stellate ganglion block(SGB)on spatial learning memory function impairment in rapid eye movement sleep deprived(RSD)rats.Methods:Thirty-two rats were randomly assigned to Control group,RSD group,SGB group,and rapid eye movement sleep deprivation with stellate ganglion block intervention(RSD+SGB)group.The rats in RSD group and RSD+SGB group were modeled by modified multi-platform method(MMPM),and the rats in SGB group and RSD+SGB group were intervened by the SGB method.Morris water maze(MWM)was selected to evaluate the spatial learning and memory functions of rats in each group,and the expression levels of glutamate(Glu)and aspartate(Asp)in hippocampal tissues of rats in each group were detected by colorimetric assay,and the expression levels of N-methyl-D-aspartate receptor 1(NR1)and caspase-3 in hippocampal tissues of rats in each group were detected by Western Blot.Results:Compared with the RSD group,rats in RSD+SGB group had a significantly shorter escape latency after SGB intervention(P＜0.05),while the number of passes through the original platform position and the percentage of target quadrant time were significantly in-creased(P＜0.05);at the same time,the hippocampal tissues'expression levels of Glu,Asp,NR1,and caspase-3 were all significantly reduced(P＜0.05).Conclusion:SGB protects against RSD-induced impairment of spatial learn-ing memory capacity by reducing hippocampal tissue excitotoxicity and apoptosis induced by excitatory amino acid hyper-activation in RSD rats.

ObjectiveTo investigate the effect and mechanism of Taohong Siwutang （TSD） on myocardial ischemia reperfusion injury （MIRI） in ovariectomized （OVX） female mice. MethodAfter the OVX model of female mice was established， the estradiol （E₂） level was detected by enzyme-linked immunosorbent assay （ELISA） to verify the model. Sixty OVX mice were randomly divided into six groups： Sham operation group， model group， low， medium， and high dose groups （9， 18， 36 g·kg^-1） of TSD， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group， with 10 mice in each group. The MIRI model was verified by a laser speckle flowmeter. The pathological changes in myocardial tissue were detected by 2，3， 5-triphenyltetrazolium chloride （TTC） and hematoxylin-eosin （HE） staining. Serum creatine kinase isoenzyme （CK-MB）， cardiac troponin Ⅰ （CTnⅠ）， malondialdehyde （MDA）， superoxide dismutase （SOD）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） levels were detected by ELISA. The expression of Nrf2 and heme oxygenase-1 （HO-1） were observed by immunofluorescence staining. The expressions of Nrf2， HO-1， apoptotic B-cell lymphomato-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， inflammatory cytokines interleukin-18 （IL-18）， and interleukin-1β （IL-1β） were detected by Western blot. ResultCompared with the sham operation group， the serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the model group were increased （P<0.01）， and the levels of SOD and IL-10 were decreased （P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were decreased （P<0.01）， and the protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were decreased. The protein expressions of Bax， IL-18， and IL-1β were increased （P<0.01）. Compared with the model group， serum levels of CK-MB， CTnⅠ， MDA， and IL-6 of TSD groups were significantly decreased （P<0.05， P<0.01）， and SOD and IL-10 were significantly increased （P<0.05， P<0.01）. TTC staining and HE staining damage scores of myocardial tissue were significantly decreased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were increased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 were significantly increased （P<0.05， P<0.01）， and those of Bax， IL-18， and IL-1β were significantly decreased （P<0.05， P<0.01）. The effect of the high dose group of TSD was the most significant. The serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the Nrf2 inhibitor group were significantly increased （P<0.05， P<0.01）， and the levels of SOD and IL-10 were significantly decreased （P<0.05， P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were significantly increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were significantly decreased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were significantly decreased， and those of Bax， IL-18， and IL-1β were significantly increased （P<0.01）. ConclusionTSD can alleviate MIRI in OVX mice， reduce oxidative stress response and the release of inflammatory factors， and inhibit apoptosis， playing a protective role in OVX mice with MIRI， which may be related to the activation of Nrf2/HO-1 signaling pathway.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

Objective To summarize the clinical features of spontaneous remission in classic fever of unknown origin (FUO). Methods Medical records of 121 patients diagnosed with FUO at admission in Peking Union Medical College Hospital between January 2018 and June 2018 were reviewed retrospectively. Patients who were discharged without etiological diagnoses were followed for 2 years. The clinical features and outcomes of these patients were summarized. Multivariate logistic regression was used to analyze related factors of spontaneous remission of FUO. Results After excluding 2 patients who lost to follow-up, the etiology of 119 FUO patients were as follows: infectious diseases in 30 (25.2％) cases, connective tissue diseases in 28 (23.5％) cases, tumor diseases in 8 (6.7％) cases, other diseases in 6 (5.0％) cases, and unknown diagnoses in 47 (39.5％) cases. Totally, 41 patients experienced spontaneous remission of fever (the median time from onset to remission was 9 weeks, ranging from 4 to 39 weeks). In patients with spontaneous remission in FUO, lymphadenopathy was less common clinical manifestation, the levels of inflammatory markers including leukocyte count, neutrophil count, neutrophil ratio, C-reactive protein, and ferritin were lower, and the proportion of CD8 positive T lymphocytes expressing CD38 was lower. Multivariate logistic regression analysis of factors with a P-value < 0.05 in univariate analysis shown that white blood cell count (OR: 0.545, 95％CI: 0.306-0.971, P = 0.039), neutrophil count (OR: 2.074, 95％CI: 1.004-4.284, P = 0.049), and proportion of neutrophils (OR: 0.928, 95％CI: 0.871-0.990, P = 0.022) were independent significant factors associated with spontaneous remission in FUO. Conclusions This study suggested that most patients discharged with undiagnosed classic FUO would remit spontaneously. Thus, for patients with stable clinical conditions, follow-up and observation could be the best choice. Patients with lower level of some inflammatory factors may have a high likelihood of spontaneous remission in classic FUO.

Objective:To investigate the predictive value of serum albumin (Alb) levels in the early postoperative period (within 1 hour) for urosepsis after minimally invasive percutaneous nephrolithotomy (mPCNL).Methods:The clinical data of 160 patients treated by single channel holmium laser mPCNL in urolithiasis treatment center of the second hospital of Tianjin Medical University from January 2019 to January 2020 were retrospectively analyzed. The patients were divided into the sepsis group and the non-sepsis group according to whether the patients developed urosepsis after the operation. There were 110 cases of male, and 50 cases of female, with average age of(51.8±11.9), including 68 cases with hypertension, 26 cases with diabetes, 12 patients with history of preoperative fever, 16 cases with history of endoscopic lithotomy surgery, 6 patients with preoperative catheter, 24 patients with positive preoperative urine culture, 12 patients with positive preoperative nitrite volume, 32 cases with preoperative routine urine leucocyte(+ + + ). The operative time and infusion volume were recorded during the operation. Blood samples were collected from all patients within 1 hour after surgery to detect blood routine and serum albumin (Alb), and the change of haemorrhagic white blood cells and serum albumin were calculated. Univariate and multivariate analyses were used to statistically analyze the relevant clinical parameters to identify the independent risk factors for urosepsis after mPCNL surgery. The ROC curve was established and the area under the comparison curve was calculated to analyze the predictive value of independent risk factors for postoperative urosepsis.Results:There were 13 patients (8.1%) in the sepsis group, including 7 males and 6 females, with an average age of (53.1±8.2) years. There were 147 patients (91.9%) in the non-sepsis group, including 103 males and 44 females, with an average age of (51.7±12.1)years. Single factor analysis showed the infectious stones (38.5% and 8.8%), surgery duration [(94.6±26.2)min and(63.6±24.5)min], a positive urine culture (46.2% and 12.2%), positive urinary nitrite (30.8% and 5.4%), strong positive urinary leukocyte (61.5% and 11.3%), postoperative albumin levels [(34.2±2.7)g/L and(40.7±6.2)g/L]and changes of serum albumin levels within one hour after surgery [(18.3±4.6)% and(3.8±14.3)%] between the sepsis group and the non-sepsis group had significant differences ( P<0.05). Multiariable logistic regression analysis showed the strong positive urine leucocyte ( OR=57.704, 95% CI 2.407-1383.427, P=0.012), postoperative blood leucocyte level within one hour after surgery ( OR=2.406, 95% CI 1.154-3.627, P=0.014) and the change of serum albumin levels after surgery ( OR=1.373, 95% CI 1.083-1.740, P=0.009) were independent risk factors for sepsis. ROC curve analysis indicated that the AUC of the change amplitude of serum albumin level was 0.926, which was significantly higher than the AUC of the qualitative results of blood leukocyte and the AUC of urinary leukocyte( P<0.01). Conclusions:The positive urinary leucocyte, the change of serum albumin levels after surgery within one hour and the leucocyte level are independent risk factors for postoperative urosepsis after mPCNL. The change of serum albumin level in the early postoperative period has a strong predictive value for the early diagnosis of postoperative sepsis.

Background Papillary thyroid cancer is the result of a variety of pathogenic factors. The prevalence of papillary thyroid cancer varies greatly in different regions, and the disease is more harmful to women. Objective This study aims to explore the relationship between reproductive factors and papillary thyroid cancer, and to provide basic data for prevention and control of the disease. Methods A 1∶1 age (±3 years) matched case-control study was conducted in 331 pairs of newly confirmed papillary thyroid cancer cases and controls from two hospitals in Shanghai from November 2012 to December 2013. Comparisons were made in the history of menstruation, pregnancy, gynecological and breast diseases, and other variables between the two groups. Results The results of univariate analysis indicated that the proportions of education below bachelor degree, married, and mainly manual workers in the case group were significantly higher than those in the control group (P<0.05); the proportion of those with a family history of thyroid diseases in the case group was significantly higher than that in the control group (P<0.05); the proportions of the cases with irregular menstruation (77.34%), a history of using oral contraceptive or hormone drugs (24.77%), a history of benign gynecological diseases (31.72%), and a history of gynecological surgery (9.67%) were significantly higher than the proportions in the control group (P<0.05). After adjusting potential confounding factors such as history of CT examination, age, kinds of family salt, total iodine intake every day, education level, occupation, marital status, body mass index, and family history of thyroid diseases, the results of multiple logistic regression analysis showed that irregular menstruation (OR=1.767, 95%CI: 1.122-2.782; P=0.014), surgical menopause (OR=12.787, 95%CI: 3.202-51.057; P<0.001), pregnancy >1 time (OR =2.490, 95%CI: 1.196-5.184; P=0.015), and the history of using oral contraceptive or hormone drugs (OR=2.389, 95%CI: 1.338-4.268; P=0.003) were the risk factors of papillary thyroid cancer. Conclusion Irregular menstruation, surgical menopause, history of pregnancy, and history of using oral contraceptive or hormone drugs might be the risk factors of papillary thyroid cancer. To reduce the incidence of papillary thyroid cancer, strengthened health education and rational use of contraceptives are recommended.

Objective: To investigate the effects of two nanotopographies of ultraviolet (UV)-treated titanium surface on macrophage biological behaviour and inflammatory cytokines secretion, and to provide basis for clinical application of UV-treatment in dental implant modification. Methods: Titanium disks were allocated into two groups. Samples in one group were acid-etched in hydrofluoric acid (Acid Ti group), and those in the other group were acid-etched and anodized (Anodization group) to form two nanotopographies respectively. The surface morphology was evaluated by field-emission scanning electron microscopy (FE-SEM). The samples were stored in the dark for 8 weeks. Thirteen samples from each group were exposed to UV-irradiation for 48 h (Acid Ti+UV group and Anodization+UV group), UV-untreated samples from Acid Ti and Anodization groups served as control. Hydrophilicity of samples was measured using contact angle measuring device. After 4, 24 and 72 h of incubation, macrophage cell adhesion and proliferation were conducted using cell counting kit-8. Cytokine/chemokine secretions [tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α)] were measured from cell culture supernatants at 24 and 72 h using magnetic luminex assay. Cell morphology was examined using FE-SEM after 2 h of incubation. Results: Micropitted/nanopillar and micropitted/nanotubular topographies were observed in Acid Ti group and Anodization group respectively. Contact angles in Acid Ti+UV and Anodization+UV groups (20.2°±2.8° and 0.0°±0.0°) were significantly smaller than those in the Acid Ti and Anodization groups (P<0.05). Cell adhesion and proliferation in all groups at 4 and 24 h showed no difference (P>0.05). Cell proliferation in Acid Ti+UV and Anodization+UV groups at 72 h were (0.92±0.13) and (1.10±0.08) respectively, which were significantly higher than those in Acid Ti and Anodization groups. TNF-α concentration in Acid Ti+UV and Anodization+UV groups at 72 h were (1.03±0.11) and (0.87±0.10) ng/L, MCP-1 were (301.7±50.3) and (240.8±18.7) ng/L, MIP-1α were (224.9±30.6) and (233.9±14.9) ng/L respectively, which were significantly lower than those in Acid Ti and Anodization groups (P<0.05). Conclusions UV treatment can increase hydrophilicity of two titanium surface topographies, especially of Anodization+UV group. UV-treated titanium surfaces can promote macrophage proliferation and reduce the inflammatory response in vitro.