[A sericin hydrogel scaffold for sustained dexamethasone release modulates macrophage polarization to promote mandibular bone defect repair in rats].

OBJECTIVE: To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone (SMH-CD/DEX) scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization. METHODS: The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-ß-cyclodextrin (NH2-ß-CD) and sericin hydrogel and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), biocompatibility assessment and drug release test. THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1, mRNA expressions of IL-6, Il-10, Arg-1 and iNOS, and surface markers CD86 and CD206 using Western blotting, RT-qPCR, and flow cytometry. In a co-culture system of human periodontal ligament stem cells (HPDLSCs) and THP-1 macrophages, the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP, Runx2, OCN and BMP2 mRNA, ALP staining, and alizarin red staining. In a rat model of mandibular bone defect, the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining. RESULTS: In THP-1 macrophages, incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions. In the co-culture system, SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation. In the rat models, implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect. CONCLUSION: The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Prognostic Value of Four Preimplantation Malnutrition Estimation Tools in Predicting Heart Failure Hospitalization of the Older Diabetic Patients with Right Ventricular Pacing.

OBJECTIVES: The prognostic value of preimplantation nutritional status is not yet known for older diabetic patients that received right ventricular pacing (RVP). The study aimed to investigate the clinical value of the four malnutrition screening tools for the prediction of heart failure hospitalization (HFH) in older diabetic patients that received RVP. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: This study was conducted between January 2017 and January 2018 at the Fuwai Hospital, Beijing, China, and included older (age ≥ 65 years) diabetic patients that received RVP for the first time Measurements: The Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Naples Prognostic Score (NPS), and the Controlling Nutritional Status (CONUT) score were used to estimate the preimplantation nutritional status of the patients. Univariate and multivariate Cox proportional hazard regression analyses were performed to investigate the association between preimplantation malnutrition and HFH. RESULTS: Overall, 231 older diabetic patients receiving RVP were included. The median follow-up period after RVP was 53 months. HFH was reported for 19.9% of the included patients. Our results showed preimplantation malnutrition for 18.2%, 15.2%, 86.6% and 66.2% of the included patients based on the PNI, GNRI, NPS, and CONUT score, respectively. The cumulative rate of HFH during follow-up period was significantly higher for patients in the preimplantation malnutrition group based on the PNI (log-rank = 13.0, P = 0.001), GNRI (log-rank = 8.5, P = 0.01), and NPS (log-rank = 15.7, P < 0.001) compared to the normal nutrition group, but was not statistically significant for those in the preimplantation malnutrition group based on the CONUT score (log-rank = 2.7, P = 0.3). As continuous variables, all the nutritional indices showed significant correlation with HFH (all P < 0.05). However, multivariate analysis showed that only GNRI was independently associated with HFH (HR = 0.97, 95% CI: 0.937-0.997, P = 0.032). As categorical variables, PNI, GNRI, and NPS showed significant correlation with HFH. After adjustment of confounding factors, moderate-to-severe degree of malnutrition was an independent predictor of HFH based on the PNI (HR = 4.66, 95% CI: 1.03-21.00, P = 0.045) and GNRI (HR = 3.02, 95% CI: 1.02-9.00, P = 0.047). CONCLUSION: Preimplantation malnutrition was highly prevalent in older diabetic patients that received RVP. The malnutrition prediction tools, PNI and GNRI, showed significant prognostic value in accurately predicting HFH in older diabetic patients with RVP.

Surgical Treatments for Femoral Shaft Fractures: A Narrative Review.

Femoral shaft fractures are increasingly common due to various traumatic injuries. Intramedullary nail (IMN) is considered the gold standard treatment for these fractures, but comorbidities often require thorough trauma life support and intensive care. The primary goal of treatment is rigid fixation, early mobilisation, and long-term functional recovery. This article reviews current concepts in the treatment of femoral shaft fractures, including the effects of early or delayed operation, differences between antegrade or retrograde intramedullary nailing, alternative methods to using a fracture table, methods to predict nail length before operation, assessing femoral rotation during an operation, and complications.

Host response of Nicotiana benthamiana to the parasitism of five populations of root-lesion nematode, Pratylenchus coffeae, from China.

In a recent survey of nematodes associated with tobacco in Shandong, China, the root-lesion nematode Pratylenchus coffeae was identified using a combination of morphology and molecular techniques. This nematode species is a serious parasite that damages a variety of plant species. The model plant benthi, Nicotiana benthamiana, is frequently used to study plant-disease interactions. However, it is not known whether this plant species is a host of P. coffeae. The objectives of this study were to evaluate the parasitism and pathogenicity of five populations of the root-lesion nematode P. coffeae on N. benthamiana.N. benthamiana seedlings with the same growth status were chosen and inoculated with 1,000 nematodes per pot. At 60 days after inoculation, the reproductive factors (Rf = final population densities (Pf)/initial population densities (Pi)) for P. coffeae in the rhizosphere of N. benthamiana were all more than 1, suggesting that N. benthamiana was a good host plant for P. coffeae.Nicotiana. benthamiana infected by P. coffeae showed weak growth, decreased tillering, high root reduction, and noticeable brown spots on the roots. Thus, we determined that the model plant N. benthamiana can be used to study plant-P. coffeae interactions.

[Clinical efficacy of split liver transplantation in the treatment of children with biliary atresia].

Objective: To compare the clinical efficacy of split liver transplantation (SLT) and living donor liver transplantation(LDLT) in the treatment of children with biliary atresia. Methods: The clinical data of 64 children with biliary atresia who underwent SLT and 44 children who underwent LDLT from June 2017 to May 2022 at Liver Surgery & Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Among the children who received SLT, there were 40 males and 24 females. The median age at transplantation was 8 months (range:4 to 168 months). Among the patients who received LDLT, there were 24 males and 20 females. The age at transplantation ranged from 4 to 24 months,with a median age of 7 months. Sixty-four children with biliary atresia were divided into two groups according to the SLT operation time: 32 cases in the early SLT group(June 2017 to January 2019) and 32 cases in the technically mature SLT group (February 2019 to May 2022). Rank sum test or t test was used to compare the recovery of liver function between the LDLT group and the SLT group,and between the early SLT group and the technically mature SLT group. The incidence of postoperative complications was compared by χ2 test or Fisher exact probability method. Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cold ischemia time(M (IQR)) (218 (65) minutes), intraoperative blood loss(175 (100) ml) and graft-to-recipient body weight ratio (3.0±0.7) in the LDLT group were lower than those in the SLT group(500 (130) minutes, 200 (250) ml, 3.4±0.8) (Z=-8.064,Z=-2.969, t=-2.048, all P<0.05). The cold ischemia time(457(158)minutes) and total hospital stay ((37.4±22.4)days) in the technically mature SLT group were lower than those in the early SLT group(510(60)minutes, (53.0±39.0)days).The differences were statistically significant (Z=-2.132, t=1.934, both P<0.05).The liver function indexes of LDLT group and SLT group showed unimodal changes within 1 week after operation. The peak values of ALT, AST, prothrombin time, activeated partial thromboplasting time, international normalized ratio, fibrinogen and creatinine all appeared at 1 day after operation, and the peak value of prothrombin activity appeared at 3 days after operation. All indicators returned to normal at 7 days after operation. The 1-,2-,and 3-year overall survival rates were 95.5% in LDLT group and 93.5% in the technically mature SLT group, and the difference was not statistically significant. The 1-,2-,and 3-year overall survival rates were 90.2% in the early SLT group and 93.5% in the technically mature SLT group, and there was no significant difference between the two groups(P>0.05). The main complications of the early SLT group were surgery-related complications(28.1%,9/32), and the main complications of the technically mature SLT group were non-surgery-related complications(21.9%,7/32). There were 5 deaths in the SLT group,including 4 in the early SLT group and 1 in the technically mature SLT group. Conclusion: The survival rate of SLT in the treatment of biliary atresia is comparable to that of LDLT.

The Resolution Rate of Pulmonary Embolism on CT Pulmonary Angiography: a Prospective Study.

PURPOSE: To prospectively assess the rate of clot resolution from CT pulmonary angiography (CTPA) in patients with acute pulmonary embolism (PE). MATERIALS AND METHODS: This prospective cohort study included 290 patients (136 men, 154 women; mean age, 51.9 years) with acute PE. All patients had a CTPA at the presentation and had at least one follow-up within 6 months (mean 72.7 days). Sixty-four percent of patients had follow-up scans for research purposes within a pre-determined period (between 28 and 184 days; mean, 78.27 days) and 36 % had (between 2 and 184 days; mean, 62.78 days) for a clinical indication. The volume of each clot was measured using a semi-automated quantification program. The resolution rate was evaluated by interval-censored analysis. RESULTS: The overall estimated probability of complete resolution was 42 % at 7 days, 56 % at 10 days, and 71 % at 45 days. Achieving complete resolution was significantly faster in patients with peripheral clots (HR: 1.78; CI: 1.05-3.03, p = 0.032) but slower in patients with consolidation and history of venous thromboembolism (VTE), (HR: 0.37; CI: 0.18-0.79, p = 0.01 and HR: 0.57; CI: 0.35-0.91, p = 0.019, respectively). Although the patients with cancer showed a faster resolution rate (HR: 1.67; CI: 1.05-2.68, p = 0.032), the mortality rate was significantly higher than non-cancer patients. CONCLUSION: The resolution rate of clot burden in acute PE was associated with patients' clinical presentation variables and CTPA imaging biomarkers. This information may be incorporated into designing a prediction rule and determining the appropriate duration of anticoagulation therapy in patients with acute PE.

[The assistant effects of porcine fibrin sealant in improving stone clearance rate in flexible ureteroscopy lithotripsy in ex vivo porcine kidney model].

Objectives: To investigate the feasibility of using a porcine fibrin sealant to wrap and remove kidney calculi fragments through an isolated porcine kidney model. Methods: In the isolated porcine kidney stone model (implanted with 100 mg, air dried, ≤1 mm human stone fragments, n=6;implanted with 100 mg, air dried, ≤3 mm human stone fragments, n=6), the ureteral soft mirror combined with the 12/14Fr UAS was used to test the effect of stone extraction using only two stone extraction methods: basket extraction (control group, ≤1 mm stone fragments, n=3; ≤3 mm stone fragments, n=3) and basket-sealant extraction (test group, ≤1 mm stone fragments, n=3; ≤3 mm stone fragments, n=3). Compare the stone removal rate and operation time of the two stone retrieval methods. The sealant was put into urine of normal human and observed. Results: Porcine Fibrin Sealant can form a gel in saline and urine and adhere and wrap stone fragments. The time of procedures of test (basket-sealant) and control (basket) group in kidneys implanted with ≤ 1 mm stone fragments were (14.0±4.2) and (29.0±0.7)min (P<0.05) stone clearance rates were (90.9±1.4)% and (48.4±15.7)% (P<0.05), respectively. In kidneys implanted with ≤ 3 mm fragments, time of procedures were (12.8±4.0) and (30.0±0)min (P<0.05) Stone clearance rates were (91.1±5.0)% and (20.7±8.0)% (P<0.05). The Sealant dissolves by itself in normal human urine and normal saline at 37 ℃ for 24 hours. Conclusion: The appropriate concentration of Porcine Fibrin Sealant assisted stone retrieval may become a new method for removing small stone fragments in retrograde intrarenal surgery.

Dual Functions of MDP Monomer with De- and Remineralizing Ability.

Methacryloyloxydecyl dihydrogen phosphate (MDP) has been speculated to induce mineralization, but there has been no convincing evidence of its ability to induce intrafibrillar mineralization. Polymers play a critical role in biomimetic mineralization as stabilizers/inducers of amorphous precursors. Hence, MDP-induced biomimetic mineralization without polymer additives has not been fully verified or elucidated. By combining 3-dimensional stochastic optical reconstruction microscopy, surface zeta potentials, contact angle measurements, inductively coupled plasma-optical emission spectroscopy, transmission electron microscopy, atomic force microscopy, and Fourier transform infrared spectroscopy with circular dichroism, we show that amphiphilic MDP can not only demineralize dentin by releasing protons as an acidic functional monomer but also infiltrate collagen fibrils (including dentin collagen), unwind the triple helical structure by breaking hydrogen bonds, and finally immobilize within collagen. MDP-bound collagen functions as a huge collagenous phosphoprotein (HCPP), in contrast to chemical phosphorylation modifications. HCPP can induce biomimetic mineralization itself without polymer additives by alternatively attracting calcium and phosphate through electrostatic attraction. Therefore, we herein propose the dual functions of amphiphilic MDP monomer with de- and remineralizing ability. MDP in the free state can demineralize dentin substrates by releasing protons, whereas MDP in the collagen-bound state as HCPP can induce intrafibrillar mineralization. The dual functions of MDP monomer with de- and remineralization properties might create a new epoch in adhesive dentistry and preventive dentistry.

The value of MRCP in children with biliary symptomatology - an essential adjunct for safe cholecystectomy.

SUMMARY: Congenital abnormalities of the biliary system are a consideration in children with biliary symptomatology. The preoperative diagnosis rate is still not satisfactory, despite progresses made in imaging technology, with the potential of biliary tract injury if surgery is indicated. The double gallbladder is a rare developmental abnormality of the biliary tract with several anatomical variations. This abnormality was accurately delineated in a 7-year-old child by MRI/MRCP, allowing the ductal anatomy to be accurately identified and safe laparoscopic cholecystectomies to be performed.

Hot saline irrigation for haemostasis in functional endoscopic sinus surgery: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis of existing evidence on the role of hot saline irrigation in patients undergoing functional endoscopic sinus surgery and its impact on the visibility of the surgical field. METHOD: A search of PubMed, Cochrane, Ovid databases and Google Scholar was performed. RESULTS: Three randomised controlled trials were included. Pooled meta-analysis demonstrated a statistically significant better visibility of the surgical field, and a reduction in total blood loss and operating time during functional endoscopic sinus surgery in the hot saline irrigation group compared with the room temperature irrigation group. Subgroup analysis of studies that did not use vasoconstrictors showed a significant reduction in total blood loss and operating time. CONCLUSION: This is the first systematic review that addresses hot saline irrigation for haemostasis in functional endoscopic sinus surgery. The results suggest that hot saline irrigation in functional endoscopic sinus surgery for chronic rhinosinusitis may significantly improve visibility of the surgical field, reduce total blood loss by 20 per cent and decrease operating time by 9 minutes. However, there are limitations of the study because of the significant heterogeneity of the methods, quality and size of the studies.

[Relevance of renal cell carcinoma angiogenesis and tumor stem cells].

Objective: To investigate the relationship between tumor angiogenesis and renal cancer stem cells. Methods: The primary cell culture method was used to extract and isolate RCSCs, and then qRT-PCR and Western blot methods were used to detect the expression levels of the kidney cancer stem cell markers CD105 and Sox2 genes and proteins from different MVD kidney cancer tissues. Using TCGA database, analyze the correlation between tumor angiogenesis markers and tumor stem cell regulatory genes. Results: The stem cell markers CD105 and Sox2 genes in RCSCs derived from high MVD kidney cancer tissues were respectively increased by (2.34±1.77) times and (3.92±1.41) times (PCD105<0.01, PSox2<0.05)and protein levels were increased by (5.12±3.31) times and (4.90±3.30) times(PCD105<0.05, PSox2<0.01).Meanwhile,up to 30% of stem cell promoting stemness regulatory genes are positively correlated with angiogenesis genes CD31/PECAM1 and KDR, and 64 genes are also strongly positively correlated with CD31/PECAM1 and KDR genes. Conclusion: The high microvessel density of kidney cancer is strongly correlated with the existence of renal carcinoma stem cells.

Observation of rotational coherence in an excited state of CO.

The vacuum ultraviolet (VUV) radiation is generated in the strong-field-ionized CO molecules through 2+1 resonance excitation with two-color femtosecond laser pulses. When scanning the relative delay between two pump pulses, the rotational-resolved VUV radiations show periodic oscillations lasting as long as 500 ps. Fourier analysis reveals that these oscillations correspond to rotational beat frequencies of the A2Πi state of CO+, which is the result of multi-channel interference during the resonant excitation process. High resolution of Fourier transform spectra up to 0.067cm-1 allows us to obtain the fine energy levels of the A2Πi state. The theoretical calculation is in good agreement with the experimental observation. This work reveals the rotational coherence of the ionic excited state and shows the prospect of rotational coherence spectroscopy in measuring fine structures of molecular ions.

Abnormalities of intrinsic brain activity in irritable bowel syndrome (IBS): A protocol for systematic review and meta analysis of resting-state functional imaging.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders affecting up to 11.5% of the general global population. The brain-gut axis has been shown to play an important role in the pathogenesis of IBS. Several studies confirmed that intrinsic brain abnormalities existed in patients with IBS. But, studies of abnormal regional homogeneity (ReHo) in IBS have reported inconsistent results. The objective of this protocol is to conduct a meta-analysis using the Seed-based d mapping software package to identify the most consistent and replicable findings of ReHo in IBS patients. METHOD: We will search the following three electronic databases: MEDLINE, EMBASE and Web of Science. The primary outcome will include the peak coordinates and effect sizes of differences in ReHo between patients with IBS and healthy controls from each dataset. The secondary outcomes will be the effects of age, illness severity, illness duration, and scanner field strength. The SDM approach was used to conduct voxel-wise meta-analysis. Whole-brain voxel-based jackknife sensitivity analysis was performed to conduct jackknife sensitivity analysis. A random effects model with Q statistics is used to conduct heterogeneity and publication bias between studies and meta-regression analyses were carried out to examine the effects of age, illness severity, illness duration, and scanner field strength. RESULTS: The results of this paper will be submitted to a peer-reviewed journal for publication. CONCLUSION: This research will determine the consistent pattern of alterations in ReHo in IBS patients.

Long-term Clinical Performance of Composite Resin or Ceramic Inlays, Onlays, and Overlays: A Systematic Review and Meta-analysis.

CLINICAL RELEVANCE: Composite resin or ceramic inlays, onlays, and overlays can achieve high long-term survival and success rates.

A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis.

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (ß = -2.5; [95% CI -4.7 to -0.4]), whereas negative symptoms were unaffected by treatment (ß = -0.39; [95% CI -2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.