A Retrospective Study of Clinical and Immunological Features of a Pediatric Population with Talaromyces marneffei Infection.

BACKGROUND: Talaromyces marneffei (T. Marneffei) infection is considered as an indicator of immunosuppression in immunocompromised individuals, leading to multiple organ damage. Our study aimed to evaluate both the clinical characteristics and immunological features of pediatric patients infected with T. marneffei from our institute, providing novel insights into diagnosis and treatment for this life-threatening disease. METHOD: Thirteen pediatric patients with T. marneffei infection were enrolled in Guangzhou Women and Children's Medical Center during 2012 to 2020. Clinical data and laboratory findings were collected and further analyzed. Pearson correlation coefficient was calculated to determine the relationship between serum immunoglobulins (Igs) levels and white blood cell count, or the absolute lymphocyte count. RESULTS: Patients were diagnosed as having T. Marneffei infection mainly based on the results of fungal culture and Gram stain of specimens. The most common presentations were fever (69%), pneumonia (38%) and immunodeficiency (38%). The total levels of Igs (IgE, IgA, and IgM) were positively correlated with both white blood cell count and absolute lymphocyte count. CONCLUSION: Serum Ig expression Pattern in patients diagnosed with T. marneffei infection might serve as an effective prognostic marker which would help with the development of early interventions for children with this fatal disease.

Acupoint stimulation for alcohol use disorder: A systematic review and meta-analysis.

BACKGROUND: To assess the effect of acupoint stimulation for Alcohol use disorders (AUD). METHODS: AUD is a complex disease that threatens the health of the global population. Acupoint stimulation, a sort of therapy applying stimulation on acupoints to produce a therapeutic effect without side effects, has been widely used in AUD patients, but its efficacy remains controversial. Electronic databases (the Cochrane Library, EMBASE, PubMed, CNKI, VIP, Wan-Fang) were systematically searched for randomized controlled trials (RCTs) on acupoint stimulation for AUD from database inception to September 30, 2022. A meta-analysis was performed using Review Manager 5.4 software. Continuous data (scales) were expressed as mean differences (MDs) or standardized mean difference (SMD) with 95% confidence intervals (95% CI). Study methodological quality was assessed according to the Cochrane risk-of-bias tool for trials. The grading of recommendations assessment, development and evaluation was used to assess the certainty of evidence for outcomes. RESULTS: A total of 16 RCTs with 1097 participants were included. Compared to psychotherapy or drug therapy alone, the combination of acupoint stimulation and other sorts of therapies presented advantages in alleviating alcohol craving (SMD = -1.09, 95% CI = -1.40 to -0.77, df = 2, P < .00001, grading of recommendations assessment, development and evaluation very low certainty), (SMD = -2.25, 95% CI = -3.17 to -1.34, df = 3, P < .00001, low certainty) and the severity of alcohol withdrawal symptoms (MD = -1.21, 95% CI = -2.32 to -0.1, df = 2, P = .03, low certainty), as well as improving anxiety (MD = -3.41, 95% CI = -4.06 to -2.76, df = 4, P < .00001, very low certainty) and depression levels (MD = -3.27, 95% CI = -4.92 to -1.62, df = 4, P = .0001, very low certainty) on patients with AUD. In addition, a greater effect was also found with the 4-week treatment courses in reducing craving (SMD = -2.18, 95% CI = -2.61 to -1.75, P < .00001, low certainty). CONCLUSION: Acupoint stimulation and its combined therapy may better relieve AUD symptoms effectively and the treatment duration should be set at more than 2 weeks. However, due to the low-quality of the included RCTs, high-quality studies are needed to further confirm it in the future.

Surgery or Surveillance for Esophageal Squamous Cell Carcinoma With Clinical Complete Response After Neoadjuvant Chemoradiotherapy.

We aimed to evaluate the role of esophagectomy in patients with esophageal squamous cell carcinoma with clinically complete response (cCR) after neoadjuvant chemoradiotherapy. Data of patients with locally advanced esophageal squamous cell carcinoma who achieved cCR after neoadjuvant chemoradiotherapy between October 2008 and September 2018 were retrospectively reviewed. The criteria for cCR include: (1) tumor resolution on computed tomography, (2) maximum standardized uptake value decrement >35% on positron-emission tomography-computed tomography scan, and (3) a negative endoscopic biopsy result. Overall survival (OS) and disease-free survival (DFS) were compared between patients who received surveillance only (surveillance) and those who underwent surgery. A total of 154 patients with cCR, including 54 in the surveillance group and 100 in the surgery group, were included. The 5-year OS rates in the surveillance and surgery groups were 47.9% and 36.9 %, respectively (P= 0.210). The 5-year DFS rates were 38.1% and 28.2%, respectively (P = 0.203). Surgery was not a prognostic factor in the multivariable analysis (OS: HR: 1.26, 95% CI: 0.69-2.33, P = 0.453; DFS: HR: 1.08, 95% CI: 0.60-1.96, P = 0.795). In the surgery group, ypT0N0, ypT+Nany, and ypT0N+ were noted in 54%, 37%, and 9% of patients, respectively. The 5-year OS rates were 55.8%, 22.2%, and 12.4%, respectively (P = 0.001). No survival differences were noted between the surveillance and surgery groups. However, 46% of cCR patients in the surgery group did not have pathological complete response, and their outcomes were poor. Esophagectomy may be the only way to identify patients with residual disease.

Survival Comparison Between Open and Thoracoscopic Upfront Esophagectomy in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear. OBJECTIVE: The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT). METHODS: The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors. RESULTS: After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching. CONCLUSION: This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.

Propensity score analysis comparing survival between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

INTRODUCTION: The purpose of the current study is to compare definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with cT1-3/N0-3 esophageal squamous cell carcinoma in survival. METHODS: Records from 2008 to 2014 of 4931 patients with clinical T1-3/N0-3 esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or esophagectomy with adjuvant chemoradiotherapy were obtained from the Taiwan Cancer Registry. Univariable and multivariable analyses were performed and propensity score matching was used to minimize the bias. Overall survival was compared between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy, and also in the three different clinical stages. RESULTS: Definitive chemoradiotherapy was performed on 4381 patients, and 550 patients received esophagectomy adjuvant chemoradiotherapy. Each group produced 456 patients for comparison after propensity score matching. The 1-year, 2-year, and 3-year overall survival rates for matched patients in with definitive chemoradiotherapy group were 57.18%, 31.92%, and 23.8%. The 1-year, 2-year, and 3-year overall survival rates for matched patients treated in the esophagectomy with adjuvant chemoradiotherapy group were 72.35%, 45.74%, and 34.04%(p<0.0001). In multivariable analysis, treatment modality was an independent prognostic factor. Esophagectomy with adjuvant chemoradiotherapy provided better survival outcome than definitive chemoradiotherapy for patients with clinical stage II/III disease. As for patients with clinical stage I disease, there was no significant survival difference between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy. CONCLUSIONS: Esophagectomy with adjuvant chemoradiotherapy provided better survival than definitive chemoradiotherapy in clinical II/III esophageal squamous cell carcinoma. However, more data are needed to conduct a convincing conclusion in clinical stage I patients.

Deer Antler Reserve Mesenchyme Cell-Conditioned Medium Reduces the Destruction of Periodontitis in Mice.

Reserve mesenchyme cells (RMCs) are a type of antler stem cells (ASCs) that contribute to the rapid growth of deer antlers, the only known mammalian organ that can fully regenerate annually. Based on the prior evidence, ASC-conditioned medium could improve regenerative cutaneous healing in rats. The purpose of the study was to evaluate the therapeutic effects of RMC-conditioned medium (RMC-CM) on reducing the destruction in the mice periodontitis (PD) model and the underlying mechanisms. The lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used in vitro to verify the effects of RMC-CM. The results revealed that RMC-CM could significantly reduce bone resorption and osteoclast activation, upregulate anti-inflammatory macrophages (M2) related interleukin (IL)-10 and CD206, and downregulate pro-inflammatory macrophages (M1) related tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase in vivo. In vitro, RMC-CM could significantly promote LPS-stimulated RAW264.7 cells migration, reduce osteoclast differentiation, downregulate the expression of TNF-α, IL-6, and IL-1ß, and upregulate the expression of IL-10 and arginase 1. According to the results, we concluded that RMC-CM could significantly reduce alveolar bone resorption and inhibit inflammation in gingival tissue by decreasing the activation of osteoclasts and inducing macrophage polarization toward the M2 phenotype. This study may serve as the experimental foundation for RMC-CM in the treatment of PD.

Combination therapy for pediatric patients with Kasabach-Merritt phenomenon: A single-center retrospective study.

This study aimed to in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor. Here, we retrospectively evaluated 12 patients with KMP in Guangzhou Women and Children's Medical Center, Guangzhou Medical University, from 2017 to 2021. 12 patients, including 7 females and 5 males, were identified. Tumors were located in the leg (n = 4), neck (n = 1), face (n = 3), chest wall (n = 1), back (n = 2), and retroperitoneum (n = 1). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation. All the patients underwent embolization therapy. Nine patients received steroid treatment and 7 patients were administered with sirolimus. The mean duration of treatment was 1.6 months. All the patients reported in this study were alive when discharged. Embolization combined with steroid and sirolimus appears effective in patients with KMP, as well as in those who experienced disease recurrence. However, a long-term follow-up of the children cured of KMP will be necessary to monitor its recurrence and improve the outcome.

Psychological Interventions on Abstinence in Patients with Alcohol Use Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Purpose: Accumulating research suggests that psychotherapy helps improve abstinence but the difference in the efficacy of multiple psychotherapies in alcohol use disorder (AUD) remains to be explored. Patients and Methods: A systematic search of databases (Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and EBSCO) for studies (published from inception to April 10th.) of adults diagnosed with AUD accepting psychotherapies was conducted. Studies covering 9 countries and regions. The qualitative analysis pooled 2646 individuals from 34 randomized controlled trials (RCTs) and the networks included 1928 participants (23 RCTs). The outcomes included percentage of days abstinent (PDA), change in drinks per drinking day (change in DDD), and change in craving compared among individuals accepting various psychotherapies. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and was registered on the International Prospective Register of Systematic Reviews (PROSPERO). Results: For the network of PDA, motivational enhancement treatment (MET) (35.44, 11.78 to 59.09, high-certainty) and couple therapy (CT) (28.89, 13.42 to 44.36, moderate-certainty) were significantly different from treatment as usual (TAU) with the surface under the cumulative ranking curve (SUCRA) mean rank 1.9 and 1.9 respectively. TAU+supportive psychotherapy (SP) was better than TAU for the change in DDD in the high-quality direct comparison. Conclusion: The motivational enhancement and the couple therapy show potential amelioration for alcohol abstinence. Additionally, the preferred interventions are different for improving PDA and change in DDD. The evidence network remains to be strengthened.

Advances of exosomes in periodontitis treatment.

Periodontitis is an inflammatory disease initiated by dysbiosis of the local microbial community. Periodontitis can result in destruction of tooth-supporting tissue; however, overactivation of the host immune response is the main reason for alveolar bone loss. Periodontal tissue cells, immune cells, and even further activated osteoclasts and neutrophils play pro-inflammatory or anti-inflammatory roles. Traditional therapies for periodontitis are effective in reducing the microbial quantities and improving the clinical symptoms of periodontitis. However, these methods are non-selective, and it is still challenging to achieve an ideal treatment effect in clinics using the currently available treatments and approaches. Exosomes have shown promising potential in various preclinical and clinical studies, including in the diagnosis and treatment of periodontitis. Exos can be secreted by almost all types of cells, containing specific substances of cells: RNA, free fatty acids, proteins, surface receptors and cytokines. Exos act as local and systemic intercellular communication medium, play significant roles in various biological functions, and regulate physiological and pathological processes in numerous diseases. Exos-based periodontitis diagnosis and treatment strategies have been reported to obtain the potential to overcome the drawbacks of traditional therapies. This review focuses on the accumulating evidence from the last 5 years, indicating the therapeutic potential of the Exos in preclinical and clinical studies of periodontitis. Recent advances on Exos-based periodontitis diagnosis and treatment strategies, existing challenges, and prospect are summarized as guidance to improve the effectiveness of Exos on periodontitis in clinics.

Outcomes of patients with different lepidic percentage and tumor size of stage I lung adenocarcinoma.

BACKGROUND: To evaluate the long-term outcomes after surgical resection for stage I lung adenocarcinoma based on the percentage of lepidic component (LC) and invasive tumor size (IS). METHODS: The clinicopathological characteristics of 1049 patients with stage I lung adenocarcinoma who underwent surgery between 2006 and 2016 were retrospectively reviewed. Tumors were categorized into groups: A (LC ≥ 50%) and B (LC < 50%). Groups A0 and A1 consisted of minimally invasive adenocarcinomas (MIA) and other lepidic-predominant invasive adenocarcinomas, respectively. Group B was categorized into B1 (IS ≤ 1 cm), B2 (1 < IS≤2 cm), and B3 (2 < IS≤3 cm) by invasive tumor size and divided into subgroups (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]) according to the presence[lep+] or absence[lep-] of LCs. Cumulative incidence of recurrence (CIR) and cancer-specific survival (CSS) were examined. RESULTS: LC decreased with increasing IS. Only 24 (8.5%) tumors in group A had an IS >1 cm. 10-year CIR and CSS were 15.2% and 86.0%. LC and IS were found to be independent predictors of CSS. Patients in group A had 1.4% 10-year CIR and 100% 10-year CSS. In group B, a significantly higher CIR and worse CSS were observed as IS increased (p < 0.001), but LC was not a predictor for CSS (p = 0.593). No significant differences in CIR or CSS were found in presence of LC or not when LC < 50% (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]: p = 0.36/0.48, p = 0.82/0.94, and p = 0.90/0.37, respectively). CONCLUSIONS: LC≥50% tumors demonstrated excellent prognosis regardless of IS. The outcomes of LC < 50% tumors were well predicted by IS, corresponding to the T-staging system. The predictive value of LC for prognosis became insignificant.

Comparing survival between neoadjuvant chemoradiotherapy followed by open or thoracoscopic oesophagectomy in patients with oesophageal squamous cell carcinoma.

OBJECTIVES: The goal of this study was to investigate the overall survival between open and thoracoscopic oesophagectomy in patients with oesophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (NCRT). METHODS: The Taiwan Cancer Registry was queried for ESCC from 2008 to 2016. We enrolled 2250 patients with ESCC receiving NCRT plus open (n = 487) or thoracoscopic (n = 1763) oesophagectomy. One-to-two propensity score matching between open and thoracoscopic oesophagectomy was performed. Overall survival was compared between the 2 groups before and after propensity score matching. Univariable analysis and multivariable analysis were performed to identify prognostic factors. RESULTS: After one-to-two propensity score matching, 353 patients were in the open group and 706 patients were in the thoracoscopic group. The 3-year overall survival rates for matched patients treated with open or thoracoscopic oesophagectomy were similar (39.18% vs 44.33%, p = 0.11). Better overall survival was associated with thoracoscopic oesophagectomy for the patients in the y-pathological complete response stage (pCR) (57.26% vs 65.19%, p = 0.045), y-pathological III stage (12.78% vs 22.31%, p = 0.028) and y-pathological T0N+ stage (15.79% vs 41.01%, p = 0.010). In multivariable analysis, surgical approach was an independent prognostic factor only before propensity score matching. After matching, surgical approach was not an independent prognostic factor. CONCLUSIONS: This propensity-matched study demonstrated that open and thoracoscopic oesophagectomies are associated with similar long-term survival in patients with ESCC undergoing NCRT. Stage-specific comparisons showed that thoracoscopic oesophagectomy is associated with better survival than open oesophagectomy in patients with the pathological complete response, y-pathological III and y-pathological T0N+ stages and with similar survival in y-pathological I/II patients.

Survival Comparison Among Neoadjuvant Chemoradiotherapy Followed by Esophagectomy, Definitive Chemoradiotherapy, and Esophagectomy Alone for Esophageal Squamous Cell Carcinoma.

BACKGROUND: For patients with locoregional esophageal squamous cell carcinoma (ESCC), survival outcomes among neoadjuvant chemoradiotherapy followed by operation (nCRT-OP), definitive chemoradiotherapy (dCRT), and esophagectomy alone remain controversial. PATIENTS AND METHODS: Information from the 2008-2016 Taiwan Cancer Registry was used. A total of 7637 cT1b-4, N0/+, M0 ESCC patients receiving nCRT-OP (n = 1955), dCRT (n = 4122), or esophagectomy alone (n = 1560) were included. Propensity score matching was performed to balance clinical variables among the three groups. Stage-specific overall survival was compared before and after propensity score matching. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Propensity score matching resulted in 1407 cases for comparison. The 5-year overall survival rates for matched patients treated via dCRT, nCRT-OP, and esophagectomy alone were 19.77%, 31.23%, and 30.52%, respectively (p < 0.001). On multivariable analysis, treatment modality was still an independent prognostic factor both before and after propensity score matching. nCRT-OP and esophagectomy alone were associated with significantly better overall survival than dCRT for locoregional ESCC patients. CONCLUSIONS: This propensity-matched study revealed that nCRT-OP and esophagectomy provided better survival than dCRT in cT1b-4, N0/+, M0 ESCC patients.

Sequence for Surgical Resection of Primary Lung Tumor for Oligometastatic Non-small Cell Lung Cancer.

BACKGROUND: Differing surgical series for the treatment of primary lung tumor with synchronous oligometastatic stage IV non-small cell lung cancer (NSCLC) have been published; however, outcomes remain ambiguous. METHODS: Patients with synchronous oligometastatic stage IV NSCLC treated from 2005 to 2017 were enrolled to identify the impact of treatment sequence (primary lung resection vs systemic treatment) on progression-free survival (PFS) and overall survival (OS). RESULTS: Tumor resection occurred in 51 patients (84% adenocarcinoma, 55% nonsmokers, and 65% driver gene mutation) before or after systemic treatment in 33 (64.7%) and 18 (35.3%) patients, respectively. Patients who received resection first were older (62.1 vs 54 years) and at a less advanced intrathoracic stage (18% vs 44%). No significant differences were noted regarding perioperative complications (30% vs 28%), hospital length of stay (9.0 vs 10.5 days), percentage of disease progression (91% vs 94%), overall death (70% vs 78%), median PFS (14.0 vs 22.8 months), and OS (44.6 vs 53.2 months). Patients with single-organ metastasis had significantly longer PFS and OS than those with oligometastases (17.5 vs 12.8 months, P = .040; and 55.6 vs 39.8 months, P = .035), respectively. Multivariable Cox analysis identified nonsolitary metastasis as the only independent predictor of PFS (hazard ratio, 2.27; 95% confidence interval, 1.07-4.81; P = .033). CONCLUSIONS: Primary lung resection before or after induction systemic therapy may benefit patients with oligometastatic NSCLC. Future randomized clinical trials examining the effect of treatment sequence is recommended.

Research progress on basic fibroblast growth factor in promoting periodontal tissue regeneration / 口腔疾病防治

@#Basic fibroblast growth factor (bFGF) exhibits superior biological functions by improving periodontal inflammation, promoting the migration and proliferation of periodontal-related stem cells, promoting the formation of blood vessels and periodontal ligament-like tissue, and regulating the formation of bone/cementum. It plays an important role in tooth development, repair and regeneration. bFGF can be combined with seed cells and scaffold materials for periodontal tissue regeneration, which has been verified in a number of experimental studies. However, the application of bFGF alone as a drug in clinical treatment requires further research.

Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration.

Periodontitis is a chronic inflammatory disease that leads to the destruction of both soft and hard periodontal tissues. Complete periodontal regeneration in clinics using the currently available treatment approaches is still a challenge. Mesenchymal stem cells (MSCs) have shown promising potential to regenerate periodontal tissue in various preclinical and clinical studies. The poor survival rate of MSCs during in vivo transplantation and host immunogenic reaction towards MSCs are the main drawbacks of direct use of MSCs in periodontal tissue regeneration. Autologous MSCs have limited sources and possess patient morbidity during harvesting. Direct use of allogenic MSCs could induce host immune reaction. Therefore, the MSC-based indirect treatment approach could be beneficial for periodontal regeneration in clinics. MSC culture conditioned medium (CM) contains secretomes that had shown immunomodulatory and tissue regenerative potential in pre-clinical and clinical studies. MSC-CM contains a cocktail of growth factors, cytokines, chemokines, enzymes, and exosomes, extracellular vesicles, etc. MSC-CM-based indirect treatment has the potential to eliminate the drawbacks of direct use of MSCs for periodontal tissue regeneration. MSC-CM holds the tremendous potential of bench-to-bed translation in periodontal regeneration applications. This review focuses on the accumulating evidence indicating the therapeutic potential of the MSC-CM in periodontal regeneration-related pre-clinical and clinical studies. Recent advances on MSC-CM-based periodontal regeneration, existing challenges, and prospects are well summarized as guidance to improve the effectiveness of MSC-CM on periodontal regeneration in clinics.

The feasibility of phage therapy for periodontitis.

Periodontitis, a chronic progressive inflammation caused by plaque biofilm, is the main cause of tooth loss in adults. For certain refractory periodontitis cases, it is difficult to achieve a good curative effect using the existing periodontal treatment approaches, which may be due to periodontal pathogenic mechanism in the affected periodontal tissue that the host cannot resist and eliminate. Various pieces of evidence collectively revealed that most studies are focusing on phages in periodontal disease. Several studies have reported periodontitis treatment using phage therapy, highlighting its features including specificity, rapid propagation, and effectiveness on bacteriophage biofilms. In this study, we focus on these reports, aiming to lay the foundation for improved periodontal treatment approaches.

Prognostic histologic subtyping of dominant tumor in resected synchronous multiple adenocarcinomas of lung.

The prognostic role of histological patterns of dominant tumor (DT) and second dominant tumor (sDT) in synchronous multiple adenocarcinoma (SMADC) of lung remains unclear. SMADC patients diagnosed between 2003 and 2015 were retrospectively reviewed. DT and sDT were defined as two maximum diameters of consolidation among multiple tumors. Histological pattern was determined using IASLC/ATS/ERS classification system. DTs were divided into low- (lepidic), intermediate- (acinar, papillary) and high-grade (micropapillary, solid) subtypes, and sDTs into non-invasive predominant (lepidic) and invasive predominant (acinar, papillary, micropapillary, solid) subtypes. During mean 74-month follow-up among 149 nodal-negative patients having SMADC resected, recurrence was noted in 44 (29.5%), with significantly higher percentage in high-grade DT (p < 0.001). Five-year overall (OS) and disease-free (DFS) survivals in low-, intermediate- and high-grade DT were 96.9%, 94.3%, 63.3% (p < 0.001) and 100%, 87.2%, 30.0%, respectively (p < 0.001). Cox-regression multivariate analysis demonstrated high-grade DT as a significant predictor for DFS (Hazard ratio [HR] 5.324; 95% CI 2.570-11.462, p < 0.001) and OS (HR 3.287; 95% CI 1.323-8.168, p = 0.010). Analyzing DT and sDT together, we found no significant differences in DFS, either in intermediate- or high-grade DT plus invasive or non-invasive sDT. DT was histologically an independent risk factor of DFS and OS in completely resected nodal-negative SMADCs.

Significance of preoperative biopsy in radiological solid-dominant clinical stage I non-small-cell lung cancer.

OBJECTIVES: The present study aimed to clarify the association between preoperative biopsy and surgical outcomes in clinical stage I non-small-cell lung cancer (NSCLC) with different proportions of ground-glass opacity (GGO). METHODS: Data on patients who underwent pulmonary resection for NSCLC from 2006 to 2016 were drawn from a prospective registered database and analysed retrospectively. Patient characteristics collected included tumour size, location and staging, surgical approach, consolidation-tumour ratio, histopathology and the presence or absence of preoperative biopsy to identify the independent prognostic factors of disease-free survival (DFS) and cancer-specific survival. A 1:1 propensity score matching was conducted between the preoperative biopsy and reference groups based on their baseline characteristics measured before the decision for preoperative biopsy. RESULTS: A total of 1427 patients were collected to achieve an overall 5-year DFS as 84.5% (median follow-up: 67.3 months), stratified to be 99.5% in the GGO-dominant group (n = 430) and 78.2% in the solid-dominant group (n = 997). Only 2 patients (0.5%) in the GGO-dominant group experienced tumour recurrence. For solid-dominant tumours matched with propensity scores (279 in preoperative biopsy vs 279 in reference group), the independent predictors of DFS included preoperative biopsy, sublobar resection, pathological staging and angiolymphatic invasion. Preoperative biopsy was a predictor of cancer-specific survival in univariable analysis but was not in multivariable analysis. Significant differences were also found between matched groups in those with late-delay surgery, but not in patients receiving preoperative biopsy with early-delay surgery (≤21 days). CONCLUSION: Preoperative biopsy may worsen surgical outcomes in patients with clinical stage I, solid-dominant NSCLC.

The Toll-like receptor ligand, CpG oligodeoxynucleotides, regulate proliferation and osteogenic differentiation of osteoblast.

BACKGROUND: This study aimed to investigate the regulation of CpG oligodeoxynucleotides (ODNs) on proliferation and osteogenic differentiation of MC3T3 cells. METHODS: The laser co-focusing and flow cytometry assay were employed to detect cell uptake of CpG ODN 2006. Twelve ODNs were sythesized, and their effects on proliferation and differentiation were detected by MTT and alkaline phosphatase (ALP) activity assay. Flow cytometry assay was used to examine the regulation of CpG ODN on cell cycle. Quantitative real-time PCR (qRT-PCR) and western blot were used to evaluate the regulation of CpG ODN on mRNA and protein expression of osteogenic differentiation genes. RESULTS: The phosphorothioate CpG ODN 2006 could efficiently enter the MC3T3 cells in 1 h and locate in the cytoplasm. The MTT assay demonstrated CpG ODNs could promote MC3T3 cell proliferation and differentiation in the early stage, and gradually attenuated along with the increase of treating time, except for BW001 and FC001. qRT-PCR assay demonstrated that all the 12 CpG ODNs could promote the relative expression level of osteogenic differentiated genes, SP7 and OCN. In addition, western blot analysis suggested the CpG ODNs of BW001 and FC001 could increase the protein expression of P27Kip1 and Runx2 and decrease the protein expression of cyclin D1. CONCLUSION: The selected CpGODNs may be a potential gene therapy for bone regeneration of periodontitis.