Synthesis of novel silver-loaded clay AgF@Hec for the prevention of dental cariesin vitro.

Dental caries, a chronic infectious disease characterized by tooth mineral loss caused by plaque, is one of the major global public health problems. Silver diamine fluoride (SDF) has been proven to be a highly effective anti-caries drug due to its high bacterial inhibition and remineralization ability. However, the SDF solution is unstable, which immensely limits its clinical application. Therefore, new silver-load clay named AgF@Hec was designed by replacing the NH3with hectorite in this study. Fourier transform infrared spectroscopy and x-ray diffraction spectroscopy were employed to confirm the structure of AgF@Hec. Dynamic light scattering analysis was used to reveal the effect of different hectorite concentrations on the stability of AgF@Hec. Moreover, AgF@Hec exhibits significant remineralization and hardness recovery of the initial carious lesions. Bacteriostatic experiments also proved that it has a significant inhibitory effect onA. Viscosus, S. mutans, S. sanguinis, S. salivarius, Lactobacillus sp.and both gram-positive and gram-negative bacteria. We therefore believed that AgF@Hec should be a promising biomaterial that can be applied in the prevention of dental caries.

[The role of Müller cells in the formation and development of macular hole].

Müller cells are important glial cells in the retina, which play important roles in maintaining the stability of the retina by mechanical support, homeostasis, and physiological metabolism, as well as protecting photoreceptor cells and retinal pigment epithelial cells. The degeneration and destruction of Müller cells are often accompanied by various retinal diseases, and the function of Müller cells is changed under pathological conditions. Based on the summary of the morphology, distribution and function of Müller cells, this article analyzes the different manifestations and changes of Müller cells in different stages of macular hole and the closely related mechanisms, aiming to clarify the role of Müller cells in the formation and development of macular hole and to provide reference for the prediction of disease progression and guidance of treatment.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on Augest 28, 2023).

[Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report].

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

[Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage â £ squamous cell carcinoma of penis].

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.

Autophagy deficiency promotes lung metastasis of prostate cancer via stabilization of TWIST1

PurposeThe role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism.MethodsThe metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis.ResultsWe identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference.ConclusionsOur research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.

Autophagy deficiency promotes lung metastasis of prostate cancer via stabilization of TWIST1.

PURPOSE: The role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism. METHODS: The metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis. RESULTS: We identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference. CONCLUSIONS: Our research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.

[Research progress of autoantibodies in primary biliary cholangitis].

Primary biliary cholangitis (PBC) is a chronic, progressive, intrahepatic cholestasis disease. Its occurrence and development are accompanied by changes in the titer of autoantibodies. However, its pathogenesis, extent of autoantibody changes and their effects are not yet fully understood. Therefore, there is a lack of effective methods for early diagnosis of PBC in patients. Finding specific PBC autoantibody markers will greatly improve the diagnostic efficiency and save early treatment time, thereby improving therapeutic effect and prognosis. This article summarizes several PBC-related serum autoantibody markers.

Correlation study between the magnetic resonance imaging features of breast cancer and expression of immune molecular subtypes.

OBJECTIVE: To investigate the correlation between breast cancer magnetic resonance imaging features and immune molecular subtypes. PATIENTS AND METHODS: A total of 129 breast cancer patients were selected as the research object. All the patients were diagnosed by histopathology. All of them had breast magnetic resonance imaging and examination data of immunohistochemical (IHC) ER, PR, HER-2, and Ki-67. The correlation of breast cancer magnetic resonance imaging features with different immune molecular subtypes was retrospectively analyzed. RESULTS: Breast cancer is divided into different molecular subtypes. There were 72 cases with Luminal A type (55.81%), 20 cases with Luminal B type (15.50%), 14 cases with HER-2+ type (HER-2 type for over-expression) (10.85%), 23 cases with TNBC type (ER, PR and HER-2 were negative) (17.84%). The magnetic resonance imaging features of breast cancer were included, the post-enhanced morphology, margins, internal enhancement features, time-signal intensity curve (TIC) and molecular subtype expression of lesions were significantly correlated with the immune molecular subtypes (C=0.602, 0.439, 0.350 and 0.407, p=0.000, 0.000, 0.006 and 0.000). Lesion morphology: Luminal A type was mainly oval, accounting for 76.39% (55/76). Luminal B type and HER-2+ type was mainly irregular, accounting for 75.00% (15/20) and 64.29% (9/14) respectively. TNBC type was mainly shown as lobulation, accounting for 60.87% (14/23). Margin of the lesion: Luminal A type was mainly smooth margin, accounting for 73.61% (53/72). Luminal B type and TNBC type were mainly irregular margin, accounting for 70.00% (14/20) and 56.52% (13/23) respectively. The margin of HER-2+ type was mainly spiculation, accounting for 64.29% (9/14). The internal enhancement features: Luminal A type was mainly even enhancement, accounting for 62.50% (45/72). Luminal B type and HER-2+ type were mainly heterogeneous enhancement, accounting for 65.00% (13/20) and 64.29% (9/14) respectively. TNBC type was mainly annular enhancement, accounting for 73.91% (17/23). TIC type: Luminal A type was mainly Type II, accounting for 66.67% (48/72). Luminal B, HER-2+ type and TNBC type was mainly Type III, accounting for 70.00% (14/20), 64.29% (9/14) and 60.87% (14/23) respectively. The clinical signs include painless breast lumps, bloody breast discharge, and orange peel-like skin changes, nipple retraction and nipple elevation. There is no significant correlation between the above signs and the expression of molecular subtypes (C=0.014, 0.129, 0.154, 0.097 and 0.057, p=0.999, 0.533, 0.447, 0.747 and 0.935 respectively), the difference is not statistically significant (p>0.05). CONCLUSIONS: The characteristics of breast cancer magnetic resonance imaging was certainly correlated with the expression of immune molecular subtypes. The breast cancer molecular subtypes can be predicted by the imaging signs, which can provide valuable information for preoperative neoadjuvant treatment of breast cancer.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

[Effects of chemotherapy combined with donor lymphocyte infusion on chronic graft-versus-host disease and prognosis in minimal residual disease positive patients after allogeneic hematopoietic stem cell transplantation].

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.

Circ-CCDC66 accelerates proliferation and invasion of gastric cancer via binding to miRNA-1238-3p.

OBJECTIVE: The aim of this study was to examine the expression of circ-CCDC66 in gastric cancer (GC) tissues and cell lines, as well as its correlation with the prognosis of GC. Moreover, the regulatory effects of circ-CCDC66 on biological behaviors of GC cells and its molecular mechanism were explored. PATIENTS AND METHODS: The relative expression level of circ-CCDC66 in GC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the circ-CCDC66 level and overall survival of GC patients was analyzed as well. The potential influences of circ-CCDC66 on proliferative and invasive abilities of GC cells were evaluated through 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assay, respectively. Meanwhile, the cell cycle progression and apoptosis of GC cells affected by circ-CCDC66 were determined. In addition, the direct target miRNA of circ-CCDC66 was predicted and verified by bioinformatics method and Dual-Luciferase reporter gene assay, respectively. RESULTS: Circ-CCDC66 was significantly up-regulated in GC tissues and cell lines. Up-regulation of circ-CCDC66 indicated markedly worse prognosis of GC patients. Transfection of circ-CCDC66-siRNA remarkably attenuated proliferative and invasive abilities of BGC-823 and MGC-803 cells. Besides, GC cells were arrested in the G0/G1 phase, and the apoptotic rate was remarkably elevated after circ-CCDC66 knockdown. The Dual-Luciferase reporter gene assay verified that circ-CCDC66 bind to miRNA-1238-3p by competing with LHX2 (LIM-homeobox domain 2). MiRNA-1238-3p was significantly down-regulated in GC cells, whereas LHX2 was up-regulated. Furthermore, overexpression of miRNA-1238-3p in GC cells markedly suppressed the LHX2 level. CONCLUSIONS: Circ-CCDC66 is highly expressed in GC tissues and cell lines. Knockdown of circ-CCDC66 attenuates proliferative and invasive abilities of GC cells. Our results indicate that circ-CCDC66/miRNA-1238-3p/LHX2 axis may be a promising target for GC treatment.

[Clinical outcomes with cruciate-substituting ultra-congruent and posterior stabilized in total knee arthroplasty].

Objective: To investigate clinical outcomes of total knee arthroplasty with ultra-congruent insert(UC) or posterior stability insert (PS). Methods: A retrospective study was performed on 97 patients (17 males, 80 females, 119 knees) with knee osteoarthritis who received total knee arthroplasty. Of the patients, 42 cases (50 knees) received UC protheses and 55 cases (69 knees) received PS protheses in total knee arthroplasty by the same surgeon in Peking University Third Hospital from March 2015 to November 2015. The data including age, gender, body mass index (BMI), range of motion (ROM), Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Hospital for Special Surgery Knee Score (HSS) before and after the surgery were collected and compared in the two groups. The data were compared between the two groups by single-sample t test. Results: There was no significant differences in age, gender, BMI, ROM, HHS and WOMAC scores between the two groups before operation(all P>0.05). At 3 months and 2 years of follow-up, ROM, HSS and WOMAC scores were significantly improved in the two groups(all P<0.05), but there was no statistical difference between the two groups(t=-0.303, -1.593, Z=-0.500, all P>0.05). One patient with PS prosthesis recieved revision surgery due to prothesis loosening; and no complication found in the UC group(χ(2)=0.731, P>0.05). Conclusion: There is no obvious difference between PS and UC in TKA, UC insert seems to be a practical alternative to the PS.

Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric cancer.

OBJECTIVE: MicroRNAs (miRNAs) play critical roles in regulating tumor development and progression. The aim of the study is to investigate the clinical significance of miR-1294 expression in gastric cancer (GC). PATIENTS AND METHODS: The expression of miR-1294 in 82 cases of GC tissues and adjacent normal tissues was determined using quantitative Real Time-PCR (qRT-PCR) analyses. Survival plot was calculated using the Kaplan-Meier methods and log-rank test from the date of operation to the time of death or last follow-up date. The association between miR-1294 expression and clinical categorical data was analyzed using the chi-squared test. Moreover, Univariate and multivariate Cox analysis were performed to assess the risk factors of GC prognosis. RESULTS: We showed that miR-1294 expression was significantly downregulated in GC tissues compared to adjacent normal tissues. The low expression of miR-1294 in patients with GC was correlated with clinicopathological parameters including larger tumor size, lymph node metastasis, and distant metastasis. Kaplan-Meier survival analysis showed that GC patients with lower miR-1294 expression exhibited a shorter disease-free survival (DFS) and overall survival (OS) time compared to those patients with higher miR-1294 expression. Multivariate Cox analysis showed that lower miR-1294 expression, tumor size, lymph node metastasis, and distant metastasis were identified as independent risk factors of GC prognosis. CONCLUSIONS: Our results provided evidence that miR-1294 expression was significantly downregulated in GC and may serve as a predictor of GC prognosis.