Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023， fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group （n＝3 750）， and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group （n＝ 3 706）. Self-reported indicators of patients were collected through telephone follow-up at 0， 4， 7 and 14 days after treatment. The improvement values of pain score， swelling score and health utility value， as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score （PSM） method was adopted to perform baseline matching on patient’s age， gender， fracture site， fracture severity， surgical type， type of hospital， and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM， a total of 6 425 patients were included， of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment， the observation group showed significant improvement in pain score （4.768 vs. 4.353）， swelling fangshiyuan2008@126.com grading score （2.979 vs. 2.391）， and life quality utility value （0.430 vs. 0.363）， as well as effective rate （87.20% vs.75.99%） compared to the control group （P＜0.05）. The results of subgroup analyses conducted by gender， age， hospital type， and fracture site were consistent with the aforementioned results. In terms of safety， the observation group had no serious adverse reactions， with a total of 29 cases of mild adverse reactions such as dizziness， stomach pain， and allergies， with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain， swelling， quality of life， and effective rate in patients with fractures， and have good safety.

Objective     To analyze the risk factors for postoperative length of stay (PLOS) after mediastinal tumor resection by robot-assisted non-endotracheal intubation and to optimize the perioperative process. Methods    The clinical data of patients who underwent Da Vinci robot-assisted mediastinal tumor resection with non-endotracheal intubation at the Department of Thoracic Surgery, General Hospital of Northern Theater Command from 2016 to 2019 were retrospectively analyzed. According to the median PLOS, the patients were divided into two groups. The univariate analysis and multivariate logistic regression were used to analyze risk factors for prolonged PLOS (longer than median PLOS). Results    A total of 190 patients were enrolled, including 92 males and 98 females with a median age of 51.5 (41.0, 59.0) years. The median PLOS of all patients was 3.0 (2.0, 4.0) d. There were 71 patients in the PLOS>3 d group and 119 patients in the PLOS≤3 d group. Multivariate logistic regression showed that indwelled thoracic catheter [OR=11.852, 95%CI (2.384, 58.912), P=0.003], preoperative symptoms of muscle weakness [OR=4.814, 95%CI (1.337, 17.337), P=0.016] and postoperative visual analogue scale>5 points [OR=6.696, 95%CI (3.033, 14.783), P<0.001] were independent factors for prolonged PLOS. Totally no tube (TNT) allowed patients to be discharged on the first day after surgery. Conclusion    Robot-assisted mediastinal tumor resection with non-endotracheal intubation can promote rapid recovery. The methods of optimizing perioperative process are TNT, controlling muscle weakness symptoms and postoperative pain relief.

Objective:To evaluate the role of NOD-like receptor 3 (NLRP3) inflammasome activation-mediated macrophage polarization in myocardial injury after ischemic stroke in diabetic mice.Methods:Wild-type C57BL/6J mice and NLRP3 -/- mice, aged 4-6 weeks, were fed a high fat diet combined with streptozotocin administration to develop the diabetic model. Twenty-four diabetic wild type C57BL/6J mice and 23 diabetic NLRP3 -/- mice were divided into wild type sham operation group (WT D-SHAM group, n=9) , wild type ischemic stroke group (WT D-MCAO group, n=15) , NLRP3 -/- sham operation group (NLRP3 -/-D-SHAM group, n=9) and NLRP3 -/- ischemic stroke group (NLRP3 -/-D-MCAO group, n=14). The ischemic stroke model was developed by middle cerebral artery occlusion in the animals anesthetized with isoflurane. Echocardiography and electrocardiography were carried out at 3, 7, 14 and 28 days after developing the model. Mice were sacrificed under deep anesthesia, and myocardial tissues were taken at 28 days after surgery for determination of the expression of macrophage marker F4/80 and M2 type macrophage marker CD206 mRNA (by real-time fluorescence quantitative polymerase chain reaction). Results:Compared with WT D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased at 28 days after surgery, and QT interval and QTc interval were prolonged at 14 and 28 days after developing the model in WT D-MCAO group ( P<0.05). Compared with NLRP3 -/-D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased, and QT interval and QTc interval were prolonged at 3 days after surgery in NLRP3 -/-D-MCAO group ( P<0.05). There was no significant difference in CD206 and F4/80 mRNA expression between WT D-SHAM group and WT D-MCAO group and between NLRP3 -/-D-SHAM group and NLRP3 -/-D-MCAO group ( P>0.05). Compared with WT D-MCAO group, the QT interval and QTC interval were significantly shortened at 14 and 28 days after developing the model, and the expression of F4/80 mRNA was down-regulated and the expression of CD206 mRNA was up-regulated at 28 days after developing the model in NLRP3 -/-D-MCAO group ( P<0.05). Conclusions:NLRP3 inflammasome activation-mediated polarization of macrophages to M2 phenotype is involved in myocardial injury after ischemic stroke in diabetic mice.

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.
Humans ; Anti-Inflammatory Agents/pharmacology* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; Lipopolysaccharides/pharmacology* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Receptors, Chemokine/metabolism* ; Stem Cells ; Interleukin-8/metabolism*

Objective:To evaluate the efficacy of individualized mini-fluid challenge test in determining the fluid responsiveness in the patients undergoing surgery in prone position.Methods:A total of 47 patients of either sex, aged > 18 yr, with boy mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective spinal surgery in prone position, were included. The volume-controlled mode was used for mechanical ventilation, and the tidal volume was set at 8 ml/kg. The hemodynamic parameters were monitored by FloTrac/Vigileo system. The patient was changed to prone position at 5 min after endotracheal intubation (T 1), hydroxyethyl starch 130/0.4 sodium chloride injection 2 ml/kg was intravenously given at 5 min of prone position (T 2), and fluid 3 ml/kg was continuously infused at 1 min after 2 ml/kg fluid infusion (T 3), and both infusion rates were 0.5 ml·kg -1·min -1. A mini-fluid challenge test was performed during T 2-T 3 period, the standard volume therapy (total infusion of liquid 5 ml/kg) was carried out from T 2 to 1 min after infusion of liquid 3 ml/kg (T 4). The rate of change in SV at T 3 time point (ΔSVT 3) was calculated relative to T 2 time point, and the rate of change in SV at T 4 time point (ΔSVT 4) was calculated relative to T 2 time point. Positive fluid responsiveness test was defined as an increase in ΔSVT 4≥10%, and patients were divided into volume response group (Rs group) and non-volume response group (NRs group). ΔSVT 3, ΔSVT 4 and stroke volume variation and pulse pressure variation at T 3 and T 4 time points were selected, the receiver operating characteristic curve predicting fluid responsiveness was generated, and the area under the receiver operating characteristic curve (AUC) was calculated. Results:Forty-one patients were finally enrolled, including 18 cases in Rs group and 23 cases in NRs group. The AUC of ΔSVT 3 determining fluid responsiveness was 0.976, with the sensitivity 0.944 and specificity 0.957. The AUC of ΔSVT 4 determining fluid responsiveness was 0.971, with sensitivity 0.889 and specificity 0.95. The AUC of stroke volume variation at T 3 and T 4 in predicting fluid responsiveness was 0.632 and 0.609, respectively. The AUC of pulse pressure variation at T 3 and T 4 predicting fluid responsiveness was 0.470 and 0.380, respectively. Conclusions:Individualized mini-fluid challenge test (2 mg/kg colloidal solution) can accurately determine the fluid responsiveness in the patients undergoing surgery in prone position.

Objective:To investigate the clinical effect of combined treatment of comminuted inferior pole patellar fracture with micro-plate and tension-band wire.Methods:A retrospective cohort study was conducted in 50 patients with comminuted inferior pole patellar fracture (AO classification of type 34-A1) admitted to First Affiliated Hospital of University of Science and Technology of China from October 2018 to October 2020, including 28 males and 22 females, aged 17-77 years［(51.4±11.5)years］. A total of 23 patients were treated with micro-plate combined with tension-band wire (Group A) and 27 patients were treated with cable wire looping combined with tension-band wire (Group B). Fracture union, union time and last follow-up evaluation of knee range of motion and Bostman score were compared between the two groups. Complications (infection, internal fixation failure, internal fixation irritation, etc.) were also observed.Results:All patients were followed up for 12-18 months［(14.1±2.1) months］. All patients had bone union, with no statistical difference between Group A［(9.9±1.8)weeks］and Group B［(10.3±1.4)weeks］in union time ( P>0.05). Knee range of motion was (129.2±9.7)° in Group A at the last follow-up, better than (122.3±11.0)° in Group B ( P<0.05). Knee Bostman score was (27.6±1.8)points in Group A, showing no statistical difference from that in Group B［(26.8±1.9)points］( P>0.05). There were no postoperative complications in Group A. Two patients with tension band shedding of Kirschner wire after fracture healing were found in Group B, with no special treatment given due to no obvious discomfort. Conclusions:For comminuted inferior pole patellar fracture, micro-plate combined with tension-band wire is more effective and provides better knee mobility with no complications of implant failure as compared with cable wire looping combined with tension-band wire. Therefore, the technique deserves clinical promotion.

Objective:To investigate the efficacy and safety of humanized CD19-specific chimeric antigen receptor T cells (hCART19s) in treating children and young adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and to analyze relevant factors affecting its curative effect and prognosis.Methods:We conducted a single-center clinical trial involving 31 children and young adult patients with R/R B-ALL who were treated with humanized CD19-specific CAR-T cells (hCART19s) from May 2016 to September 2021.Results:Results showed that 27 (87.1%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) one month after CAR-T cell infusion. During treatment, 20 (64.5%) patients developed grade 1-2 cytokine release syndrome (CRS) , and 4 (12.9%) developed grade 3 CRS. Additionally, two patients had grade 1 neurological events. During the follow-up with a median time of 19.3 months, the median event-free survival (EFS) was 15.7 months (95% CI 8.7-22.5) , and the median overall survival (OS) was 32.2 months (95% CI 10.6-53.9) . EFS and OS rates were higher in patients who have undergone hemopoietic stem cell transplantation (HSCT) than in those without [EFS: (75.0 ± 12.5) % vs (21.1 ± 9.4) %, P=0.012; OS: (75.0 ± 12.5) % vs (24.6 ± 10.2) %, P=0.035]. The EFS and OS rates were significantly lower in patients with >3 treatment lines than in those with <3 treatment lines [EFS: 0 vs (49.5±10.4) %, P<0.001; OS: 0 vs (52.0±10.8) %, P<0.001]. To the cutoff date, 12 patients presented with CD19 + relapse, and 1 had CD19 - relapse. Conclusion:hCART19s are effective in treating pediatric and young adult R/R ALL patients, with a low incidence of severe adverse events and reversible symptoms. Following HSCT, the number of treatment lines can affect the long-term efficacy and prognosis of pediatric and young adult R/R ALL patients.

AIM: To guide the multiple imputation of missing data in clinical longitudinal studies and its sensitivity analyses, and highlight the importance of sensitivity analyses by taking the clinical trial of Qizhitongluo Capsule in treating ischemic stroke as an example. METHODS: To implement PROC MI process in SAS to perform multiple imputation and its sensitivity analysis. RESULTS: In the example, after multiple imputation, improvements in lower limb motor scores of the Qizhitongluo group were greater than those of the placebo group (all P<0.01), and the results of two sensitivity analyses under "missing not at random" were consistent with those under "missing at random". CONCLUSION: Multiple imputations combined with sensitivity analyses can ensure a robust result. It is recommended that clinical researchers perform sensitivity analyses after filling missing data.