Towards artificial intelligence to multi-omics characterization of tumor heterogeneity in esophageal cancer.

Esophageal cancer is a unique and complex heterogeneous malignancy, with substantial tumor heterogeneity: at the cellular levels, tumors are composed of tumor and stromal cellular components; at the genetic levels, they comprise genetically distinct tumor clones; at the phenotypic levels, cells in distinct microenvironmental niches acquire diverse phenotypic features. This heterogeneity affects almost every process of esophageal cancer progression from onset to metastases and recurrence, etc. Intertumoral and intratumoral heterogeneity are major obstacles in the treatment of esophageal cancer, but also offer the potential to manipulate the heterogeneity themselves as a new therapeutic strategy. The high-dimensional, multi-faceted characterization of genomics, epigenomics, transcriptomics, proteomics, metabonomics, etc. of esophageal cancer has opened novel horizons for dissecting tumor heterogeneity. Artificial intelligence especially machine learning and deep learning algorithms, are able to make decisive interpretations of data from multi-omics layers. To date, artificial intelligence has emerged as a promising computational tool for analyzing and dissecting esophageal patient-specific multi-omics data. This review provides a comprehensive review of tumor heterogeneity from a multi-omics perspective. Especially, we discuss the novel techniques single-cell sequencing and spatial transcriptomics, which have revolutionized our understanding of the cell compositions of esophageal cancer and allowed us to determine novel cell types. We focus on the latest advances in artificial intelligence in integrating multi-omics data of esophageal cancer. Artificial intelligence-based multi-omics data integration computational tools exert a key role in tumor heterogeneity assessment, which will potentially boost the development of precision oncology in esophageal cancer.

Assessment of soft and hard tissue changes following micro crestal flap-Alveolar ridge preservation and augmentation at molar extraction sites in patients with stage III/IV periodontitis: A randomized controlled trial.

AIM: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy. MATERIALS AND METHODS: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery. RESULTS: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%). CONCLUSIONS: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

Ridge preservation in periodontally compromised molar sockets with and without primary wound closure: A comparative controlled clinical trial.

OBJECTIVE: This study aimed to compare hard- and soft-tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. MATERIALS AND METHODS: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. RESULTS: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3 , whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3 . Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. CONCLUSIONS: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR-ONN-16009433).

Associations between the keratinized mucosa width and the underlying alveolar bone dimensions at partial edentulous molar sites: a retrospective cross-sectional study.

BACKGROUND: The assessment of hard and soft tissue at edentulous sites is important for subsequent implant treatment design. The aim of the present study was to explore the associations between the keratinized mucosa width (KMW) and the underlying alveolar bone dimensions at partial edentulous molar sites. METHODS: In this retrospective study, a total of 110 patients with at least one missing molar were selected. The buccal KMW of the edentulous molar sites was evaluated. Cone-beam computed tomography scans were collected, and the height discrepancy between the alveolar crest and the buccal bone plate (HC-B) as well as the alveolar bone height (ABH) were measured. The KMW was compared among the HC-B and ABH groups at both maxillary and mandibular sites. Linear regression and generalized estimation equations (GEEs) were used to explore the associations between the KMW and alveolar bone dimensions at α = 0.05. RESULTS: Among the 110 patients, 158 edentulous molar sites were analyzed. The average HC-B and ABH were significantly lower at the maxillary sites (1.26 ± 1.62 mm, 11.62 ± 3.94 mm) than at the mandibular sites (3.67 ± 2.85 mm, 14.91 ± 3.01 mm, p < 0.001). The KMW was significantly lower at sites with HC-B > 2 mm than at sites with HC-B ≤ 2 mm both in the maxilla and mandible (p < 0.001). No significant differences were found between the KMW at sites with ABH < 10 mm and sites with ABH ≥ 10 mm (p > 0.05). Linear regression and GEEs analyses revealed that the HC-B was significantly associated with the KMW (B = -0.339, p < 0.001), while the association between the KMW and the ABH was not statistically significant (B = -0.046, p = 0.352). CONCLUSIONS: The buccal KMW at edentulous molar sites was significantly associated with the HC-B. Alveolar ridges presenting with a sloped configuration were more prone to possess a narrower band of keratinized mucosa. Both hard and soft tissue augmentation should be considered for implant treatment at these sites. The correlations of dynamic changes between the KMW and alveolar bone dimensions after tooth extraction should be further investigated.

Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer's disease.

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (AD), whole-exome sequencing was performed in 215 early-onset AD (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOAD. Both variants are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation and are classified as pathogenic. Furthermore, we found significantly decreased protein levels of PDE11A in brain samples of AD patients. Expression of PDE11A variants and knockdown experiments with specific short hairpin RNA (shRNA) for PDE11A both resulted in an increase of AD-associated Tau hyperphosphorylation at multiple epitopes in vitro. PDE11A variants or PDE11A shRNA also caused increased cyclic adenosine monophosphate (cAMP) levels, protein kinase A (PKA) activation and cAMP response element-binding protein phosphorylation. In addition, pretreatment with a PKA inhibitor (H89) suppressed PDE11A variant-induced Tau phosphorylation formation. This study offers insight into the involvement of Tau phosphorylation via the cAMP/PKA pathway in EOAD pathogenesis and provides a potential new target for intervention.

Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease.

BACKGROUND: The identification of pathogenic mutations in Alzheimer's disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer's disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aß production; however, these genetic defects occur in only about 10-20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure. METHODS: We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aß and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining. RESULTS: We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aß retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21T209S/T209S mice, possibly contributing to Aß production. Palmitoyltransferase inhibitors reversed synaptic function impairment. CONCLUSIONS: ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.

CCL2 is a key regulator and therapeutic target for periodontitis.

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Mucosal bleeding correlates with submucosal microbial dysbiosis in peri-implant mucositis of patients with periodontitis.

OBJECTIVES: This study aimed to investigate the relationship between microbial communities and the severity of peri-implant mucosal bleeding in peri-implant mucositis. MATERIALS AND METHODS: Submucosal plaque samples were collected from 54 implants divided into the healthy implant (HI) group, peri-implant mucositis (PM) group, and peri-implantitis (PI) group. Sequencing of 16S rRNA was performed using the Illumina MiSeq platform. Alpha diversity (i.e., Shannon and Chao index) and beta diversity were used to measure microbial diversity within and between microbial communities, respectively. Differences in microbial taxa between groups were assessed via linear discriminate analysis effect size. Correlation between the modified sulcus bleeding index (mSBI) and microbial dysbiosis index (MDI) was examined using Spearman correlation analysis and linear models. RESULTS: The submucosal bacterial richness (Chao index) was positively correlated with the mean mSBI in the PM group. As the mean mSBI increased in the PM group, the beta diversity became closer to that of the PI group. In the PM group, the abundances of 47 genera were significantly correlated with the mean mSBI, and the MDI was positively associated with the mean mSBI. Fourteen of the forty-seven genera were discriminative taxa between the HI and PI groups, and the abundances of these biomarkers became closer to those in the PI group in the progression of peri-implant disease. CONCLUSIONS: A higher mSBI value corresponded to a higher risk of microbial dysbiosis in peri-implant mucositis. The biomarkers identified may be useful for monitoring the progression of peri-implant disease.

Uniportal versus multiportal video-assisted thoracoscopic segmentectomy for non-small cell lung cancer: a systematic review and meta-analysis.

It remains controversial whether one-port video-assisted thoracoscopic surgery (VATS) or multiportal VATS is better for segmentectomy in patients with early non-small cell lung cancer (NSCLC). We conducted this meta-analysis of eight published studies to compare the clinical effectiveness and safety of the two surgical approaches. The uniportal group had a shorter postoperative hospital stay (mean difference (MD): - 0.40, 95% CI [- 0.71 to - 0.08] days, p = 0.01), lower postoperative pain scores on day 3 (MD: - 0.90, 95% CI [- 1.26 to - 0.54], p < 0.00001) and day 7 (MD: - 0.33, 95% CI [- 0.62 to - 0.04], p = 0.02), fewer days of chest tube drainage (MD: - 0.47, 95% CI [- 0.78 to - 0.15] days, p = 0.004), and a smaller wound (MD: - 0.73, 95% CI [- 1.00 to - 0.46] cm, p < 0.00001) than the multiportal group. However, there were no significant differences between the groups in complications, operative times, resected lymph nodes, resected lymph node stations, blood loss, postoperative pain scores on days 1, 2, 30, overall survival (OS), or disease-free survival (DFS). The most common complications were prolonged air leakage (10.29%), bleeding (8.82%), vascular injury (7.14%), empyema (5.88%), and arrhythmia (5.26%) in the uniportal group. Overall, uniportal VATS appears to be better than multiportal VATS for segmentectomy in patients with NSCLC, with better postoperative outcomes and similar survival rates.

Preoperative hypoalbuminemia in patients undergoing cardiac surgery: a meta-analysis.

The preoperative serum albumin level has been shown to be associated with adverse postoperative complications, meaning that hypoalbuminemia may also be a risk factor. We performed a meta-analysis to evaluate the association of serum albumin levels with survival and complication rates after cardiac surgery. Relevant articles were identified through seven databases. Twenty studies with 22553 patients (hypoalbuminemia group, n = 9903; normal group, n = 12650) who underwent cardiac surgery met the inclusion criteria after screening. The primary outcomes were that hypoalbuminemia was significantly correlated with serious long-term all-cause mortality (hazard ratio [HR]: 1.95 [1.54-2.48]; P < 0.00001) and increased mortality (risk ratio [RR] = 1.91 [1.61-2.27], P < 0.00001). Hypoalbuminemic patients with cardiopathy were more likely to suffer postoperative complications (bleeding, infections, renal injury, and others) than those whose serum albumin levels were normal. Furthermore, hypoalbuminemia increased the time in the intensive-care unit (ICU) (mean difference [MD] = 1.18 [0.49-1.87], P = 0.0008), length of hospital stay (LOS) (MD = 3.34, 95% CI: 1.88-4.80, P < 0.00001), and cardiopulmonary bypass time (CPB) (MD = 12.40 [1.13-23.66], P = 0.03). Hypoalbuminemia in patients undergoing cardiac surgery appears to have a poor all-cause mortality or increased risk of complications. Adjusted perioperative serum albumin levels and treatment strategies for this high-risk population have the potential to improve the survival.

Resequencing of 301 ramie accessions identifies genetic loci and breeding selection for fibre yield traits.

Ramie is an important fibre-producing crop in China; however, the genetic basis of its agronomic traits remains poorly understood. We produced a comprehensive map of genomic variation in ramie based on resequencing of 301 landraces and cultivars. Genetic analysis produced 129 signals significantly associated with six fibre yield-related traits, and several genes were identified as candidate genes for respective traits. Furthermore, we found that natural variations in the promoter region of Bnt14G019616 were associated with extremely low fibre abundance, providing the first evidence for the role of pectin methylesterase in fibre growth of plants. Additionally, nucleotide diversity analysis revealed that breeding selection has been markedly focussed on chromosome 9 in which ~ 39.6% sequence underwent selection, where one gibberellin-signalling-repressed DELLA gene showed distinct selection signatures in the cultivars. This study provides insights into the genetic architecture and breeding history of fibre yield traits in ramie. Moreover, the identification of fibre yield-related genetic loci and large-scale genomic variation represent valuable resources for genomics-assisted breeding of this crop.

USP18 promotes tumor metastasis in esophageal squamous cell carcinomas via deubiquitinating ZEB1.

The dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability of most cellular proteins, have been implicated in many human diseases, including cancers. Ubiquitin-specific protease 18 (USP18), a member of the DUBs family, functions as a potential tumour promoter in various cancers. However, the biological function and clinical significance of USP18 in esophageal squamous cell carcinomas (ESCC) are still unclear. Here, we found that ESCC tumors had higher USP18 expression compared with that of normal esophageal epithelial tissues, and high USP18 level was significantly correlated with malignant phenotype and shorter survival in patients with ESCC. In functional experiments, USP18 knockdown significantly inhibited ESCC invasion and metastasis in vitro. Consistently, a xenograft assay showed that knockdown of USP18 in ESCC cell suppressed their dissemination to lung tissue in vivo. Furthermore, we showed that USP18 promoted ESCC cell metastasis by inducing ZEB1 mediated epithelial-mesenchymal transition (EMT). Importantly, our results demonstrated that the oncogenic effect of USP18 in ESCC is partially dependent on ZEB1 enhancement. Mechanistic investigations revealed that USP18 directly bound ZEB1 and decreased its ubiquitination to enhance the protein stability of ZEB1 in ESCC cells. Overall, our data highlighted an essential role of USP18 in ESCC metastasis, suggesting that it could be a potential diagnostic and therapeutic target for ESCC.

Critical roles for CCR2 and the therapeutic potential of cenicriviroc in periodontitis: A pre-clinical study.

AIM: CCR2 plays important roles in many inflammatory and bone metabolic diseases, but its specific role in periodontitis is unknown. In the present study, we aimed to explore the role of CCR2 in the progression of periodontitis and evaluate the effect of cenicriviroc (CVC) on periodontitis. MATERIALS AND METHODS: The expression of CCR2 was studied in patients with periodontitis and in ligation-induced murine model of periodontitis. The role of CCR2 in promoting inflammation and bone resorption in periodontitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC in the prevention and treatment of periodontitis was evaluated by systemic and local medication. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry were used for histomorphology, molecular biology, and cytology analysis, respectively. RESULTS: In this study, we demonstrated that CCR2 was highly expressed in human and murine periodontitis and that CCR2 deficiency was associated with decreased inflammatory monocyte and macrophage infiltration and inflammatory mediators, osteoclast number and alveolar bone resorption. Prevention and treatment with CVC significantly reduced the severity of periodontitis, regardless of whether it was administered systemically or locally. CONCLUSIONS: CCR2 plays an important role in the development and progression of periodontitis, and CVC is a potential drug for the prevention and treatment of periodontitis.

The efficacy and toxicity of maintenance therapy with bevacizumab plus pemetrexed versus bevacizumab/pemetrexed alone for stage IIIB/IV nonsquamous non-small cell lung cancer: A meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Whether maintenance therapy with bevacizumab (Bev) + pemetrexed (Pem) can achieve greater clinical benefits than Bev or Pem alone for stage IIIB/IV nonsquamous non-small cell lung cancer (NSCLC) remains unclear. We assessed the antitumour effect and toxicity of maintenance Bev+Pem versus maintenance with single-agent Bev/Pem in this meta-analysis. METHODS: Appropriate randomized controlled trials (RCTs) were screened using electronic databases (Google Scholar, PubMed, Embase, Scopus, ScienceDirect, Ovid MEDLINE, Cochrane and Web of Science). The endpoints were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). RESULTS AND DISCUSSION: We included six RCTs that contained 2,447 patients receiving induction therapy with platinum-based combination therapies. The maintenance therapy Bev+Pem group had prolonged PFS (HR = 0.74, 95% CI 0.69-0.80, p < 0.00001) and OS (HR = 0.91, 95% CI 0.83-0.99, p = 0.02) compared with the Bev/Pem group. Moreover, we further analysed the PFS rate (PFSR) and OS rate (OSR) and found that the Bev+Pem group exhibited improved PFSR-0.5y, PFSR-1y, PFSR-1.5y, PFSR-2y and OS-2y, with preferable trends in OS-1y, OS-3y and OS-4y compared with the Bev/Pem single-agent maintenance therapy. In addition, subgroup analyses indicated that the Bev+Pem group had greater PFS and OS among patients aged <65 years, patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, and patients who never smoked. Regarding adverse events (AEs), the Bev+Pem group exhibited an increased occurrence of anaemia, fatigue, thrombocytopenia and anorexia. WHAT IS NEW AND CONCLUSION: For stage IIIB/IV nonsquamous NSCLC patients, maintenance therapy with Bev+Pem offers an increased survival outcome (PFS, OS) compared with monotherapy. However, the increased incidence of AEs should not be neglected.

Modified posterior approach of the knee in patients with diffuse pigmented Villonodular synovitis: case series of a single Institution's experience.

BACKGROUND: Diffuse pigmented villonodular synovitis (DPVNS) is a challenging tumor-like disorder that mainly occurs in the anterior aspect of the knee joint. The growth may sometimes extend to the posterior knee joint. Surgical excision is the mainstream treatment for DPVNS, and the posterior approach of tumor excision is adopted when the dominant tumor shows posterior extension. However, the optimal surgical approach over the posterior knee remains unknown. METHODS: Patients with DPVNS of the knee joint who received the posterior approach of synovectomy from 1995 to 2019 were retrospectively reviewed to describe the modified separate posterior (SP) approaches, and evaluate the treatment outcomes in a case series of DPVNS knees. The results of the SP approach was also compared with those of traditional direct posterior (DP) approach. Postoperative functional outcomes were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) standardized questionnaire and clinician-completed Musculoskeletal Tumor Society (MSTS) functional rating system at outpatient department. RESULTS: A total of 20 DPVNS knees were included. Thirteen patients who received SP approaches were included in the SP group, while seven patients who received the DP approach were included in the DP group. The median follow-up times were 5.7 years (IQR, 2-8.8) in the SP group and 3 years (IQR, 2-5.3) in the DP group. Both groups showed satisfactory safety. The SP group presented higher postoperative mean WOMAC (91.23 ± 7.20) and mean MSTS (24.23 ± 2.68) than the DP group (mean WOMAC: 76.00 ± 16.57; mean MSTS: 22.43 ± 4.69). The Wilcoxon signed-rank test was use to compare preoperative and postoperative range of motion (ROM) for each group. The significant difference in SP group (p = 0.004) was found while p = 0.131 in DP group. CONCLUSIONS: The SP approach provides an effective approach with satisfactory outcomes for the surgical treatment of DPVNS knees.

Effects of preoperative needle biopsy for lung cancer on survival and recurrence: a systematic review and meta-analysis.

Needle biopsy (NB) is used for the diagnosis of lung cancer, but there is still controversy about its effect on the prognosis after surgery. We conducted this meta-analysis to compare the prognosis of lung cancer patients who underwent preoperative NB with that of those who did not. We systematically searched seven databases and Google Scholar for eligible studies. Recurrence-free survival (RFS) and overall survival (OS) were analyzed as primary outcome measures. Nine articles with a collective total of 13,541 patients (NB group, n = 4550; non-NB group, n = 8991) were included in our meta-analysis. OS [hazard ratio (HR) = 1.43 (0.96, 2.12), p = 0.08] and RFS (HR = 1.59 [1.25, 2.01], p = 0.0001) tended to be better in the non-NB group than in the NB group. Pleural recurrence (risk ratio (RR) = 2.40 [1.42, 4.07], p = 0.001) was significantly lower in the non-NB group than in the NB group. The recurrence analysis data did not reach significance, but the overall trend was better for the non-NB group. These findings demonstrate that NB is detrimental to the survival prognosis of lung cancer patients and increases the chance of pleural recurrence.

Ridge preservation in maxillary molar extraction sites with severe periodontitis: a prospective observational clinical trial.

OBJECTIVES: To assess alveolar bone changes and treatment modality alterations after ridge preservation on maxillary molar extraction sockets with severe periodontitis, compared to natural healing. MATERIAL AND METHODS: Thirty-six maxillary infected-molar teeth either receiving ridge preservation (RG group) or undergoing natural healing (NT group) were investigated. Cone-beam computed tomography (CBCT) scanning was performed immediately after surgery (the baseline) and repeated 6 months later to measure the linear and volumetric changes of the sockets. RESULTS: Based on radiographic measurements, alveolar bone width decreased by 1.58 ± 4.61 mm in the NT group but increased by 3.74 ± 4.17 mm in the RG group (p < 0.05). Significant increases in ridge height at the center of both the NT (7.54 ± 4.54 mm) and RG (9.20 ± 3.26 mm) groups were observed. Mean sinus pneumatization was 0.19 ± 0.45 mm in the RG group and 0.59 ± 0.63 mm in the NT group (p < 0.05). The relative increase in total ridge volume was 8.0% and 35.5% in the NT and RG group, respectively (p < 0.05). Implant placement with additional sinus augmentation procedure was performed in 16.7% of the RG group cases, whereas 50% in the NT group cases. CONCLUSIONS: Ridge preservation in the maxillary molar extraction sockets with severe periodontitis can improve alveolar ridge dimensions and decrease the necessity of advanced regenerative procedures at implant placement compared to natural healing. CLINICAL RELEVANCE: Ridge preservation on maxillary molar extraction sockets with severe periodontitis maintained the vertical bone height more efficiently and resulted in less need for sinus augmentation procedures at 6 months compared to natural healing.

A metabolite panel that differentiates Alzheimer's disease from other dementia types.

INTRODUCTION: Alzheimer's disease (AD) is associated with altered metabolites. This study aimed to determine the validity of using circulating metabolites to differentiate AD from other dementias. METHODS: Blood metabolites were measured in three data sets. Data set 1 (controls, 27; AD, 28) was used for analyzing differential metabolites. Data set 2 (controls, 93; AD, 92) was used to establish a diagnostic AD model with use of a metabolite panel. The model was applied to Data set 3 (controls, 76; AD, 76; other dementias, 205) to verify its capacity for differentiating AD from other dementias. RESULTS: Data set 1 revealed 7 upregulated and 77 downregulated metabolites. In Data set 2, a panel of 11 metabolites was included in a model that could distinguish AD from controls. In Data set 3, this panel was used to successfully differentiate AD from other dementias. DISCUSSION: This study revealed an AD-specific panel of 11 metabolites that may be used for AD diagnosis.

Designing cross-region ecological compensation scheme by integrating habitat maintenance services production and consumption-A case study of Jing-Jin-Ji region.

Establishing a practicable ecological compensation scheme is crucial to raise sufficient funds for habitat conservation. This study proposes a cross-region ecological compensation scheme by integrating habitat maintenance services production and consumption. In addition, the suitability evaluation method and InVEST model of habitat quality were employed to estimate the habitat maintenance services production and consumption, respectively. We used 1980 as the benchmark year and applied the scheme to a three-level hierarchy of the Jing-Jin-Ji region for 2000, 2008 and 2013. At the provincial level, Beijing paid the most habitat maintenance services ecological compensation, with an increasing trend from 1.64 × 109 RMB to 2.22 × 109 RMB, and Hebei received the most, from 2.06 × 109 RMB to 2.72 × 109 RMB. At the municipal level, Chengde, which is the most underdeveloped region in Hebei, was the largest beneficiary, receiving 1.31 × 109 RMB, 1.42 × 109 RMB and 1.46 × 109 RMB, respectively, and the ratio of ecological compensation to fiscal revenue was 7.59%. At the county level, Fengning and Weichang, the top two underdeveloped counties in Chengde, received the highest compensation. The results are consistent with each region's ecological function positioning and economic development status of the Jing-Jin-Ji region. This study can clarify the ecological responsibilities and rights, and provides the suggestions for establishing the cross administrative region ecological compensation scheme and long-term funding mechanism for habitat conservation.