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Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease in which collagen progressively deposits in the supporting framework of the lungs. The pathological collagen creates a recalcitrant barrier in mesenchyme for drug penetration, thus greatly restricting the therapeutical efficacy. On the other hand, this overloaded collagen is gradually exposed to the bloodstream at fibrotic sites because of the vascular hyperpermeability, thus serving as a potential target. Herein, pathological collagen targeting and penetrating liposomes (DP-CC) were constructed to deliver anti-fibrotic dual drugs including pirfenidone (PFD) and dexamethasone (DEX) deep into injured alveoli. The liposomes were co-decorated with collagen binding peptide (CBP) and collagenase (COL). CBP could help vehicle recognize the pathological collagen and target the fibrotic lungs efficiently because of its high affinity to collagen, and COL assisted in breaking through the collagen barrier and delivering vehicle to the center of injured sites. Then, the released dual drugs developed a synergistic anti-fibrotic effect to repair the damaged epithelium and remodel the extracellular matrix (ECM), thus rebuilding the lung architecture. This study provides a promising strategy to deliver drugs deep into pathological collagen accumulated sites for the enhanced treatment of IPF.

Objective: To investigate the effect of miR-146a on the sensitivity of breast cancer cells to paclitaxel (PTX). Materials and Methods: The mRNA expressions of miR-146a in normal breast cancer cells...

We aimed to evaluate the reliability of laryngoscopic features of vocal fold atrophy as assessed by novice otolaryngology trainees and expert laryngologists.Two expert fellowship-trained laryngologists and three non-expert otolaryngology resident trainees were recruited to view 50 anonymised laryngo-stroboscopic examinations of patients presenting with dysphonia and non-voice, laryngeal complaints. Reviewers were asked to stratify the patient's age, provide an opinion about the presence of age-related vocal fold atrophy and specify which laryngoscopy features were present to make the diagnosis.Tertiary care laryngology practice.Two fellowship-trained laryngologists and three trainee otolaryngologists.Accuracy of age categorisation was determined and Kappa analysis was performed to assess inter-rater agreement.The mean age of patients was 54.9 years old with near equal male to female distribution. The overall accuracy of age category determination by raters was only 30.8%. Kappa analysis demonstrated fair agreement regarding the presence of vocal fold atrophy in non-expert reviewers, and moderate agreement amongst expert reviewers. Features of glottic gap, muscular atrophy of vocal folds and prominent vocal processes were all identified with high agreement (80.0%).Our study illustrates that while raters can agree on the presence of age-related vocal fold atrophy, the findings may be non-specific and do not necessarily correlate with age.

The prognosis of bladder cancer patients is strongly related to both the immune-infiltrating cells and the expression of lncRNAs. In this study, we analyzed the infiltration of immune cells in 403 bladder cancer samples obtained from TCGA by applying the ssGSEA to these samples, then dividing them into high/low immune cell infiltration groups. Based on these groupings, we found 404 differentially expressed immune infiltration-related lncRNAs, which were successively analyzed by univariate Cox regression, then Least Absolute Shrinkage and Selection Operator (LASSO), and finally stepwise multiple Cox regression. Then 12 differentially expressed immune infiltration-related lncRNAs were identified and used to construct a prognostic signature for bladder cancer. Subsequently, Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, and multivariate time-dependent ROC analyses (for 1, 3, 5 years) all revealed that this signature performed well in predicting overall survival and served as an independent prognostic factor for patients with bladder cancer. Finally, both TIMER and CIBESORT showed that this 12-lncRNA prognostic signature for bladder cancer was associated with the infiltration of immune cell subtypes. Besides, nomogram considered risk score and clinical characteristics was assembled and showed great performance. More importantly, we found our signature could well distinguish the drug response of patients with bladder cancer. High risk patients showed a better response to cisplatin, doxorubicin, and anti- CTLA4 immunotherapy, low risk patients showed a better response to methotrexate and anti-PD1 immunotherapy compared with each other.

To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP).Prospective, multi-institutional cohort study.Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence.The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites.RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location.3 Laryngoscope, 132:2403-2411, 2022.

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).

The previous three decades have witnessed a prosperity of contralateral C7 nerve (CC7) transfer in the treatment of upper-extremity paralysis induced by both brachial plexus avulsion injury and central hemiplegia. From the initial subcutaneous route to the pre-spinal route and the newly-established post-spinal route, this surgical operation underwent a series of innovations and refinements, with the aim of shortening the regeneration distance and even achieving direct neurorrhaphy. Apart from surgical efforts for better peripheral nerve regeneration, brain involvement in functional improvements after CC7 transfer also stimulated scientific interest. This review summarizes recent advances of CC7 transfer in the treatment of upper-extremity paralysis of both peripheral and central causes, which covers the neuroanatomical basis, the evolution of surgical approach, and central mechanisms. In addition, motor cortex stimulation is discussed as a viable rehabilitation treatment in boosting functional recovery after CC7 transfer. This knowledge will be beneficial towards improving clinical effects of CC7 transfer.

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.

Autophagy is a highly conserved process for maintaining cellular homeostasis. Upregulation of autophagy promotes metastasis by promoting the cancer stem cell state while also stimulating tumor cell migration and invasion. We hypothesized that autophagy upregulation would be critical for cancer stem cell maintenance as well as cellular migration and invasion in thyroid cancer.Validated papillary (MDA-T32, MDA-T68), follicular (FTC-133), and anaplastic (ATC-8505c) human thyroid cancer cell lines in culture were first assessed for autophagic capacity after bafilomycin clamping. Cancer stem cells were quantified by flow cytometry for aldehyde dehydrogenase and thyrosphere formation assay. Scratch migration and Matrigel invasion assays were performed in the presence of known autophagy inhibitors: Lys05, chloroquine, and FIP200siRNA.Autophagy activity was observed across all cell lines. Thyrosphere formation, aldehyde dehydrogenase activity, and CD44 expression were reduced with inhibition of autophagy in MDA-T32, MDA-T68, FTC-133, and 8505c cells. Similarly, cell migration and invasion were attenuated: 42% (FIP200siRNA), 78% (Lys05), P.001 in MDA-T32 cells; 54% (FIP200siRNA), 67% (Lys05), P.001 in MDA-T68 cells; 73% (FIP200siRNA), 71% (Lys05), P.001) in FTC-133 cells; and 60% (FIP200siRNA), 90% (Lys05), P.001 in 8505c cells. Invasion assays demonstrated a 73%, 39%, 75%, and 65.1% reduction in the presence of Lys05 in T32, T68, FTC-133, and 8505c cells, respectively. We observed similar reductions in invasion with FIP200siRNA: 61%, 62%, 55%, and 81.4% in T32, T68, FTC-133, and 8505c cells.Autophagy is upregulated across multiple thyroid cancer subtypes. In thyroid cancer cell lines, inhibition of autophagy attenuates cancer stem cell viability, cell migration, and invasion suggesting a role for autophagy in the progression of thyroid cancer. Greater understanding of autophagy regulation in thyroid cancer will aid in developing targeted therapeutics.

Recently, various metal peroxide nanomaterials have drawn increasing attention as an efficient hydrogen peroxide (H

Background Transmission of malignancy is a notable problem that cannot always be absolutely predicted at the time of transplantation. In particular, donor-derived transmission of synovial sarcoma in solid-organ transplantation is a rare but catastrophic event. Case presentation We are the first to report three cases of synovial sarcoma transmitted from a single multi-organ donor in China. The donor died of respiratory failure caused by an intrathoracic tumor, which was diagnosed as benign at the time of donation. All three recipients developed synovial sarcoma 3–13 months after transplantation; all three cases were confirmed to be donor transmitted. The liver transplant recipient died of tumor metastasis after partial-allograft hepatectomy. The two renal-transplant recipients survived after comprehensive therapy, including allograft nephrectomy, withdrawal of immunosuppressants and targeted therapy with anlotinib. Conclusions This report highlights the importance of detailed donor assessment, close follow-up and timely treatment of unexpected donor-transmitted malignancy. Although pathology is the most important evidence for the exclusion of donors for malignant potential, it should be combined with tumor type, tumor size and speed of growth. Organs from donors with malignant potential should be discarded. Allograft nephrectomy should be considered after confirmation of renal-allograft synovial sarcoma. Anlotinib for synovial sarcoma seems to be effective and well tolerated during long-term follow-up.

Statement of problem The immediate loading protocol for 2-implant mandibular overdentures has been widely reported. Nevertheless, the clinical effects reported in different articles are quite different. Purpose The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical effects of immediate and delayed loading of 2-implant mandibular overdentures. Material and methods The review followed the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). PubMed, Cochrane Library, Web of Science, Embase, Scopus, ScienceDirect, CBM, CNKI, and Wan Fang databases were searched electronically for RCTs published before March 25, 2020. Two authors independently conducted literature screening, quality assessment, and data extraction. The outcomes of interest were implant failure rate, marginal bone loss (MBL), implant stability quotient (ISQ), periotest value (PTV), and patient satisfaction. Results A total of 2498 unduplicated records were identified. After full-text analysis, 7 eligible RCTs were included. All studies were followed for at least 12 months, and the meta-analysis was based on this. The meta-analysis showed that the implant failure rate in the immediate group was higher than that in the delayed group, but there was no statistically significant difference (I2=0%; n=7; risk difference [RD]=0.03; 95% confidence interval [CI]=-0.01 to 0.08). The difference of MBL between immediate and delayed loading was not significant (I2=88%; n=6; mean difference [MD]=-0.04; 95% CI=-0.16 to 0.24). Because of the limited articles reporting on ISQ, PTV, and patient satisfaction, no quantitative analysis was conducted for these outcomes. Conclusions Although the implant failure rate was more likely to favor the delayed group, available evidence indicates no statistical difference in implant failure and marginal bone loss between immediate and delayed loading protocols.

Traditional pathogenic diagnosis presents defects such as a low positivity rate, inability to identify uncultured microorganisms, and time-consuming nature. Clinical metagenomics next-generation sequencing can be used to detect any pathogen, compensating for the shortcomings of traditional pathogenic diagnosis. We report third-generation long-read sequencing results and second-generation short-read sequencing results for ascitic fluid from a patient with liver ascites and compared the two types of sequencing results with the results of traditional clinical microbial culture. The distribution of pathogenic microbial species revealed by the two types of sequencing results was quite different, and the third-generation sequencing results were consistent with the results of traditional microbial culture, which can effectively guide subsequent treatment. Short reads, the lack of amplification and enrichment to amplify signals from trace pathogens, and host background noise may be the reasons for high error in the second-generation short-read sequencing results. Therefore, we propose that long-read-based rRNA analysis technology is superior to the short-read shotgun-based metagenomics method in the identification of pathogenic bacteria.

The transient receptor potential canonical (TRPC) channels have been implicated in various types of malignancies including gastric cancer (GC). However, the detailed mechanisms of TRPC channels underlying cell proliferation and apoptosis of GC cells remain largely unknown. Here, we report that TRPC3 was highly expressed in clinical GC specimens and correlated with GC malignant progression and poor prognosis. Forced expression of TRPC3 in GC cells enhanced both receptor-operated Ca2+ entry (ROCE) and store-operated Ca2+ entry (SOCE) and promoted the nuclear factor of activated T cell 2 (NFATc2) nuclear translocation by AKT/GSK-3β and CNB2 signaling. Pharmacological inhibition of TRPC3 or CRISPR/Cas9-mediated TRPC3 knockout effectively inhibited the growth of GC cells both in vitro and in vivo. These effects were reversible by the rescue of TRPC3 expression. Furthermore, we confirmed the role of TRPC3 and the ROCE-AKT/GSK3β-CNB2/NFATc2 signaling cascade in regulating cell cycle checkpoint, apoptosis cascade, and intracellular ROS production in GC. Overall, our findings suggest an oncogenic role of TRPC3 in GC and may highlight a potential target of TRPC3 for therapeutic intervention of GC and its malignant progression.

Background. Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet. Method. In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers. Results. A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC. Conclusions. This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy.

AMA GC5000BTX was used to monitor the mixing ratio of benzene, toluene, ethylbenzene

The results of PD-1/PD-L1 inhibitor combined with chemotherapy for TNBC are controversial. Therefore, a meta-analysis was conducted to evaluate the efficacy and safety after PD-1/PD-L1 inhibitors plus chemotherapy in TNBC patients.We systematically searched seven databases and several mainly oncology conferences for prospective clinical trials of chemotherapy combined with immunotherapy to treat TNBC, and we included pathologic complete response (PCR), progression-free survival (PFS), overall survival (OS) and adverse effects as outcome indicators of the study.We analyzed data from six studies involving 4,187 patients. The efficacy analysis indicated that PD1/PD-L1 inhibitor combined with chemotherapy significantly increased PCR rates in neoadjuvant patients (OR: 1.60; 95% CI: 1.18-2.17; p=0.003). There was no correlation between increases in PCR rates and the expression of PD-L1, but the PCR rate was higher in PD-L1+ patients. Subgroup analysis suggested that the lymph node-positive (OR: 2.52; 95% CI: 1.69-3.77; p0.001) and ECOG PS 0 (OR: 1.9; 95% CI: 1.42-2.53; p0.001) subgroups benefited from the combination of PD-1/PD-L1 inhibitor plus chemotherapy. In TNBC receiving advanced rescue treatment, PFS was higher in the group receiving PD-1/PD-L1 inhibitor plus chemotherapy than in the group receiving chemotherapy alone (HR: 0.78; 95% CI: 0.70-0.86; p0.001). Compared with chemotherapy alone, PD-1/PD-L1 inhibitors combined with chemotherapy did not increase the OS of patients (HR=0.88, 95% CI: 0.76~1.03, p=0.12). In addition, the toxicity analysis showed that more grade 3-4 adverse effects and severe adverse effects occurred in the PD-1/PD-L1 inhibitor combined with chemotherapy group.PD-1/PD-L1 inhibitors combined with chemotherapy can improve the PCR and PFS rate of TNBC patients, but did not improve the OS, and had a higher risk of AEs.

Upregulation of heat shock proteins (HSPs) drastically compromises the treatment effect of mild photothermal therapy (PTT). Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP-silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium-dependent glucose transporter (SGLT) "valve", effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two-pronged strategy of SGLT inhibitor and ROS storm, LIK066-loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.

Tobacco smoking is positively correlated with nonalcoholic fatty liver disease (NAFLD)(1–5), but the underlying mechanism for this association is unclear. Here, we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. Notably, we identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. B. xylanisolvens colonization reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and thus increasing intestinal ceramide formation, which contributes to NAFLD progression. Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine capable of metabolizing nicotine. These findings suggest a possible avenue to reduce tobacco smoking-exacerbated NAFLD progression.

To study the effect of orthodontic treatment with extraction on root resorption and alveolar bone morphology of the central incisor in adult patients.Eleven adult patients receiving orthodontic treatment were enrolled, and asked to take cone-beam CT(CBCT) scanning before and after treatment. Root resorption of the upper and lower central incisors after treatment, changes in alveolar bone thickness and height of alveolar bone were measured and compared. Statistical analysis was performed using SPSS 23.0 software package.The length of the tooth and root was reduced to a certain degree. The change in root length of the maxillary incisor was larger than that of the mandibular incisor. The alveolar bone width of the lingual and palatal neck of the central incisor showed some reduction, and alveolar bone width of the palatal neck of the upper central incisor and the middle lingual side of the mandibular central incisor changed to a certain extent. The width of the alveolar bone in the middle labial side of the mandibular central incisor increased, but the alveolar bone on the lingual and palatal side increased after orthodontic treatment, which was more obvious than that of the maxillary central incisor.Orthodontic treatment with tooth extraction is accompanied by a certain degree of root resorption of the central incisor and alveolar bone on the lingual and palatal side. However it is also accompanied by an increase in the amount of alveolar bone on the labial side. More fenestration and dehiscence are observed in the mandible.

BK virus (BKV) is one of the most common pathogens in post-transplantation infections. For kidney transplantation, BKV infection results in the impairment of allograft function and thus increases the risk of allograft loss. However, clinical evaluation of the prognosis of BKV-associated allograft impairment is difficult. In the present study, differential plasma proteins were screened using proteomic methods from ten patients with a transition from BKV-negative to BKV activation. We identified 12 differentially expressed proteins, and S100A8 and S100A9 were the top two upregulated proteins. Data from a cross-sectional study with 66 BKV-negative and 66 BKV-positive recipients of renal transplantation indicated that plasma S100A8/A9 was upregulated in BKV-infected recipients. Plasma S100A8/A9 positively correlated with the 1 month creatinine increase (ρ = 0.499,iP/i= 0.021) and negatively correlated with the 1 month estimated glomerular filtration rate change (ρ = -0.618,iP/i= 0.003) in recipients with BK viremia. Using least absolute shrinkage and selection operator regression models, we found that S100A8/A9 was an independent risk factor for the decrease in allograft function after BKV infection. In conclusion, S100A8/A9 is a potential host biomarker for the clinical evaluation of BKV-associated allograft function impairment in kidney transplantation.

To investigate the differences between temporomandibular articular fossa bone surface and the envelope surface of the mandibular condyle movement.Thirty-four healthy adults underwent skull base and mandible scans using CBCT and performed mandibular border movement using the mandibular movement recording system. Landmarks of the fossa and tubercle were indicated and distance and angle parameters were measured on the 3D models reconstructed from the CBCT. The condyle movement envelope surfaces were formed according to models reconstructed from CBCT and the mandibular movement trajectory using computer simulation. The highest and lowest points of the envelope surface were indicated to create parameters. The data were analysed using a paired t test in SPSS (version 24.0, IBM, Armonk, NY, USA).The mandibular fossa bone surface was statistically different to the envelope surface for the height of the first peak of the envelope surface (3.280 ± 1.319 mm) and depth of the mandibular fossa (6.338 ± 2.389 mm) (the ratio was 51.75%), the height of the second peak of the envelope surface (1.463 ± 0.745 mm) and the height of the tubercle (2.000 ± 0.968 mm) (the ratio was 73.15%), and the downwards angle of the envelope surface (25.933 ± 7.539 degrees) and the posterior slope angle of the articular tubercle (35.059 ± 5.224 degrees) (the ratio was 73.97%).The downwards angle of the envelope surface was statistically significantly smaller than the posterior slope angle of the articular tubercle, suggesting that the condyle movement is flatter than the mandibular fossa bone surface.

Objective To evaluate and compare the value of quantitative parameters of preoperative dual-energy CT and MRI on KRAS mutation in rectal cancer,and to explore the correlations between postoperative pathological indicators and KRAS mutation. Methods This study retrospectively analyzed 50 patients with rectal cancer confirmed by surgery and pathology and receiving KRAS genetic testing in Lanzhou University Second Hospital from August 2017 to April 2021.According to the results of genetic testing,the patients were assigned into a wild-type group (29 patients) and a mutant type group (21 patients).The preoperative baseline data included sex,age,and serum tumor markers,and the postoperative pathological data included pathological stage,lymphovascular invasion,perineural invasion,and lymph node metastasis.The quantitative parameters of three-phase energy spectral CT included iodine (water) concentration,water (iodine) concentration,effective atomic number,and normalized iodine concentration.The quantitative parameters of apparent diffusion coefficient (ADC) included minimum ADC,average ADC,and relative ADC.In addition,the width of the superior rectal vein was obtained from the CT images of the venous phase,and the tumor segmentation,the maximum axial length of tumor,and the maximum longitudinal length of tumor were obtained from the MRI images.The qualitative and quantitative data were compared by

Breast cancer is the quintessential example of how molecular characterization of tumor biology guides therapeutic decisions. From the discovery of the estrogen receptor to current clinical molecular profiles to evolving single-cell analytics, the characterization and compartmentalization of breast cancer into divergent subtypes is clear. However, competing with this divergent model of breast cancer is the recognition of intratumoral heterogeneity, which acknowledges the possibility that multiple different subtypes exist within a single tumor. Intratumoral heterogeneity is driven by both intrinsic effects of the tumor cells themselves as well as extrinsic effects from the surrounding microenvironment. There is emerging evidence that these intratumoral molecular subtypes are not static; rather, plasticity between divergent subtypes is possible. Interconversion between seemingly different subtypes within a tumor drives tumor progression, metastases, and treatment resistance. Therapeutic strategies must, therefore, contend with changing phenotypes in an individual patient’s tumor. Identifying targetable drivers of molecular heterogeneity may improve treatment durability and disease progression.

The development of novel sonosensitizers with outstanding reactive oxygen (ROS) generation capacity and great biocompatibility poses a significant challenge for the clinical practice of sonodynamic therapy (SDT). In this work, hemoglobin (Hb) with natural metalloporphyrin was first shown to possess great potential as a sonosensitizer. Compared with traditional organic sonosensitizers, Hb had satisfactory sono-sensitizing efficiency because four the porphyrin molecules were separated by four polypeptide chains. This effectively avoided the problem of low ROS quantum yield caused by the stacking of hydrophobic porphyrins. Meanwhile, Hb is an efficient and safe oxygen carrier that may release O2 at hypoxic tumors site, which improved tumor oxygenation and subsequently enhanced SDT efficacy. Therefore, Hb was integrated with zeolitic imidazolate framework 8 (ZIF-8) to form a nanoplatform that demonstrated a potent suppression effect on deep-seated tumors under ultrasound irradiation.

Background Chordoma is a rare mesenchymal malignancy, with a high recurrence rate and unclear tumorigenic mechanism. Genetic alterations, epigenetic regulators, and chromatin spatial organization play crucial roles in the initiation and progression of chordoma. In the current study, we aim to uncover the novel therapeutical targets for chordoma via using integrated multi-omics analysis. Methods The RNA-sequencing (RNA-seq), assay for transposable accessible chromatin by high-throughput sequencing (ATAC-seq), and Hi-C were performed between chordoma and human nucleus pulposus (HNP), along with imageological examination and clinical information. The expressions of identified targets were validated by clinical samples and their functions were further evaluated by cell and animal experiments via gene knockdown and inhibitors. Results The integrated multi-omics analysis revealed the important roles of bone microenvironment in chordoma tumorigenesis. By comparing the hierarchical structures, CA2 (carbonic anhydrase II) and THNSL2 (threonine synthase-like 2) were identified in the switched compartments, cell-specific boundaries, and loops. Additionally, CA2 was highly expressed in chordoma but barely found in HNP. The cell growth and migration of chordoma cells were dramatically suppressed via inhibition of CA2 either with genetic deletion or pharmaceutical treatment with Dorzolamide HCl. Furthermore, Dorzolamide HCl also regulated the bone microenvironment by blocking the osteoclast differentiation of bone marrow monocytes. Conclusion This study uncovers the roles of bone microenvironment in the chordoma tumorigenesis and identifies CA2 as a novel therapeutic target for chordoma. Besides, our findings suggest Dorzolamide HCl as a promising therapeutic option for chordoma.

Chemotherapy remains the primary treatment of advanced solid cancer, including lung cancer. However, as first-line treatment, cisplatin-based therapy is restricted by the frequent development of drug resistance. Increasing data showed that the programmed cell death protein ligand 1 (PD-L1) plays a vital role in regulating cisplatin resistance. However, the underlying mechanisms are not fully understood. We found that miR-526b-3p expression declined while PD-L1 was elevated in cisplatin-resistant lung cancer compared to that in cisplatin-sensitive lung cancer by analyzing clinical samples. Significantly, miR-526b-3p was associated with response to cisplatin negatively. We further demonstrated that miR-526b-3p reversed cisplatin resistance, suppressed metastasis, and activated CD8+ T cells in a STAT3/PD-L1-dependent manner. Thus, our findings extended the knowledge of PD-L1-mediated cisplatin resistance of lung cancer. In addition, the introduction of miR-526b-3p provided a new clue to improve the anti-tumor effects of the combination of immunotherapy and chemotherapy.

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1 -methyladenosine (m1 A), 5-methylcytosine (m5 C), N6 -methyladenosine (m6 A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1 A-, m5 C- and m6 A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1 A-, m5 C- and m6 A-related regulators may also be promising biomarkers for future research.

Colorectal cancer (CRC) is one of the most common cancer types globally with a 5‐year survival rate of, We identified two differentially methylated regions (DMRs) between colorectal cancer samples and normal controls using a sliding window method. Receiver operating characteristic (ROC) analysis suggests these two DMRs have potential for distinguishing cancers from normal controls using both the TCGA dataset and our validation set.

Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg’s tests (p = 0.296) and Egger’s tests (p = 0.097). This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

Background Survivin have been shown to play a crucial role in rheumatoid arthritis (RA); however, the regulatory mechanism of survivin in RA has not been fully elucidated. This study aims to investigate the effect of survivin on the proliferation and apoptosis of human RA fibroblast-like synoviocyte (RA-HFLS) cells in RA and its underlying mechanism through the NOTCH pathway. Methods The RA synovial tissues of 65 RA patients with partial resection of synovium of knee joint by arthroscopy were collected. The expression of survivin in synovial tissue was detected by immunohistochemistry, and the correlation of survivin expression and clinical-pathological parameters of patients was analyzed. In vitro, the proliferation of HFLS and RA-HFLS were detected by MTT; the apoptosis of HFLS and RA-HFLS were detected by flow cytometry; the expression of survivin proteins, key protein factors (Notch1, Jagged1, Hes1) in the Notch pathway, and angiogenesis-related proteins (vascular endothelial growth factor receptor 1 [VEGFR1], Ang1, Ang2) were determined by western blot. Results We found that survivin was highly expressed in RA synovial tissues and RA-HFLS cells, and was positively correlated with erythrocyte sedimentation rate, cyclic citrullinated peptide, C-reactive protein, Disease Activity Score of 28 joints and other pathological indexes. Knockdown survivin induces RA-HFLS cell apoptosis, suppresses proliferation and the expression of VEGFR1, Ang1, Ang2. In addition, blocking Notch pathway using FLI-06 significantly down-regulated survivin expression. When survivin is up-regulated, it promotes RA-HFLS cell proliferation, the expression of VEGFR1, Ang1, Ang2 and suppresses apoptosis by activating the NOTCH. Conclusion This study confirmed that survivin promotes RA-HFLS cell proliferation, the expression of angiogenesis-related proteins and suppresses apoptosis by activating the NOTCH pathway.

Objective To use image registration techniques to study the clavicular rotation of the shoulders in the sagittal plane. Methods From 28 April 2019 to 20 May 2019, 13 healthy adults (7 males and 6 females) with no history of shoulder trauma surgery or chronic pain were recruited. Patients’ ages ranged from 22 to 42 years, with a mean age of 26.5 years. Three‐dimensional composite images of the sternum–clavicle–humerus were taken using CT images of upper limb movement in the sagittal plane in the 13 healthy adults. Four different postures were registered: (i) anatomical supine position; (ii) elbow joints lifted anteriorly in the supine position; (iii) posterosuperior hyperextension of the elbow joints in the prone position; and (iv) posteroinferior hyperextension of the elbow joints in the prone position. Image data from the humerus and clavicle in three of the postures were processed to calculate Euler angles for movements in the sagittal plane. SPSS 19 was used to perform statistical analyses. Results There was no significant difference in the angles of change in the clavicle and humerus between the dominant and non‐dominant sides under different movement patterns. For upper limb movements in the sagittal plane, the clavicle displayed different Euler angles in different postures. The rotation angle from the anatomical to the horizontal position was the smallest angle, with an average value of 7.1°, whereas the rotation angle from horizontal to posterosuperior hyperextension was the largest, with an average value of 37.2°. When the upper limb moved from anterior protraction to a posterosuperior extension, the intrinsic rotation angle of the clavicle reached its maximum, with an average value of 27.9°; when moved from the anatomical to the horizontal position, 9.1% of the sagittal rotation was executed by the clavicle. During rotation from the horizontal position to posterosuperior hyperextension and from the anatomical to posterior extension, the clavicle showed relatively higher weights at 29.5% and 37.0%, respectively. Conclusion Our results showed that dominance was not a consideration when studying clavicular rotation. Image registration is an effective method that can be used to study upper limb scapular movements. Through comparing and analyzing the data, two postures had relatively large changes in the rotation angle. This can help improve indicators of clavicular rotational function during physical examinations and postoperative functional evaluations., Image registration is an effective method that can be used to study upper limb scapular movements. Through comparing and analyzing the data, two postures had relatively large changes in the rotation angle. This can help improve indicators of clavicular rotational function during physical examinations and postoperative functional evaluations.

OBJECTIVE: To establish an intelligent cervical vertebra maturity assessment system, and to evaluate the reliability and clinical value of the system. METHODS: Sixty children aged 8-16 years were recruited in the study. Lateral cephalometric radiograph and cone beam CT (CBCT) were taken at the same period. Based on the CBCT data, the system automatically extracted the patient’s facial area through Otsu’s method, intercepted the sagittal plane by three-dimensional least squares method, captured the second to fourth cervical vertebrae by superpixel segmentation. And then selected points were marked automatically through morphological algorithm and manual method. Consistency test was performed on the two sets of data to compare the reliability of automated cervical morphology capture. According to the parameters of morphological identification, positioning and staging algorithms were designed to form the intelligent cervical vertebra maturity assessment system. The cervical vertebra maturity was also judged manually on the lateral cephalometric radiograph. The weighted Kappa test and the Gamma correlation coefficient were subsequently applied to evaluate the consistency and correlation. RESULTS: The results showed that the cervical vertebra features automatically captured based on CBCT data had a high accuracy on the overall morphological recognition. In the prediction of 8 inflection points out of 13 points, there was no significant difference between automatic and manual method on both X and Y axes (all P>0.05). The assessment results of the cervical vertebra maturity of the intelligent system had strong consistency and correlation with the manual recognition results (weighted Kappa value=0.877, Gamma value=0.991, both P

Antihypertensive agents are frequently prescribed in kidney transplant recipients (KTRs). However, the frequency and patterns of prescribing antihypertensive agents remain uncharacterized in KTRs in China. Therefore, this investigation was carried out.Retrospective prescription data dated 2011 to 2018 from KTRs in China were accessed using the Hospital Prescription Analysis Program database. Information about sex, birth date, and identification number of the patient; city, date, and department of the medical visit; major diagnoses; and the generic names, specifications, quantities, and usage of prescribed drugs were collected. Antihypertensive agents were grouped into 5 classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics. The frequency and patterns of prescribing these antihypertensive agents were analyzed.Prescriptions from 174,749 KTRs (67.2% male; mean age, 42.5 [9.4] years) were obtained, and 58.2% of the patients were prescribed antihypertensive agents. The percentage of patients who received antihypertensive treatment increased from 52.9% in 2011 to 61.6% in 2018 and varied by city. Cyclosporine was associated with higher prescription frequency of antihypertensive agents than was tacrolimus (71.7% vs 63.4%; P 0.0001). During the 8-year study period, CCBs were most frequently prescribed (39.0%), followed by ARBs (31.9%), BBs (14.3%), ACEIs (11.6%), and diuretics (3.2%). The mean (SD) number of antihypertensive drugs prescribed per KTR was 1.7 (0.8). Almost half of KTRs (51.2%) received just 1 antihypertensive drug. Co-administration of 2 or more antihypertensive drugs presented an obviously upward trend. The most commonly prescribed 2-drug combination was CCB + ARB (44.8%), followed by CCB + BB (20.1%) and CCB + ACEI (13.0%). In the patients who received 3 antihypertensive drugs, the 2 most frequently prescribed combinations were CCB + ARB + BB (37.5%) and CCB + ARB + ACEI (32.7%). Specific data varied by both year and city.The prescribing patterns of antihypertensive agents in KTRs varied by city even within same country. Hence, more high-quality research studies on the use of antihypertensive agents in KTRs are needed.

Restenosis induced by neointimal hyperplasia is one of the key reasons limiting the long-term success of cardiovascular interventional therapy. However, it remains a serious challenge to completely overcome restenosis because of the dilemma of simultaneously activating human umbilical vein endothelial cells (HUVECs) and inhibiting human aortic smooth muscle cells (HASMCs). Herein, we developed a targeted nanomedicine encapsulating the liver X receptor (LXR) agonist, T0901317, for differentially regulating the behaviors of HUVECs and HASMCs. The stimulatory effect on HUVEC proliferation/migration and the inhibitory effect on HASMC proliferation/migration were confirmed

Without smoke-free legislation in Wuhan, China, we investigated secondhand smoke (SHS) exposure at home, school, and public places for never-smoking school-going adolescents in 2019. A cross-sectional study was carried out within the Global Youth Tobacco Survey (GYTS) framework. Weighted univariate, bivariate and multivariable analyses were conducted. The prevalence of SHS exposure among never-smoking adolescents at home, school and public places was 25.7%, 31.9% and 48.9%, respectively. Multivariable logistic regression analysis showed that parents smoking, peers smoking and observing teachers smoking in school were all significantly related to a higher probability of SHS exposure at home, school, and public places. Never-smoking adolescents who had smoking parents had 14 times (adjusted odds ratio [aOR], 14.00; 95% confidence interval [CI], 11.37–17.24) higher odds of SHS exposure at home; Never-smoking adolescents who observed teachers smoking in school had about 10 (aOR = 9.76; 95% CI = 7.13–13.36) and four times (aOR = 3.55; 95% CI = 2.77–4.55) higher odds of SHS exposure in school and public places, respectively. Adopting comprehensive smoke-free legislation in public places and smoke-free home rules and implementing and supervising smoke-free school policies may further reduce SHS exposure among adolescents.

Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria–lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46−/− cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

Background Although the relatively high incidence of coronal fractures in the supracondylar–intercondylar fractures is well established, little is currently known about the morphology of those fractures. Herein, we characterized the coronal fractures in AO/OTA type 33-C3 and assessed their differences with Busch–Hoffa fractures (33-B3). Methods We retrospectively collected 61 cases of AO/OTA type 33-B or C fractures with coronal plane fragments and generated three-dimensional fracture maps of those with coronal fractures based on CT imaging and measured angle α (the angle between the coronal fracture and the posterior condyle axis in the axis plane) and angle β (the angle between the coronal fracture and the posterior femoral cortex in the sagittal plane). Results Thirty-three cases (32%) of AO/OTA type 33-C fractures contained coronal fragments. Most of them were type 33-C3 fractures. Angles α and β for type 33-C3 were significantly smaller than for type B3 at the lateral condyle, while the angles at the medial condyle were not significantly different. The fracture maps showed that the coronal fractures and the articular comminution area were more anterior in type 33-C3. Conclusions The incidence of coronal fractures was 32% and 67% in AO/OTA types 33-C and 33-C3, respectively. Our findings suggest that coronal fractures differed between both types, emphasizing the potential need for different treatment approaches.

Objective Adjuvant chemotherapy is necessary for radical resection of intrahepatic cholangiocarcinoma (ICC) with a high risk of recurrence (T2–4, N1). However, its use in the treatment of early-stage ICC remains controversial. This study aimed to investigate the role of adjuvant chemotherapy after radical resection in patients with early-stage ICC (T1N0M0). Data and methods The data of 148 patients with pathologically diagnosed ICC (T1N0M0) who underwent radical resection from January 2012 to January 2018 at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Using consistent baseline data, Kaplan–Meier survival curves were constructed to compare relapse-free survival (RFS) and overall survival (OS) between patients who received postoperative adjuvant chemotherapy (AC group) and those who received only surgical treatment (non-AC group). Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors affecting survival. The RFS and OS of patients were analyzed after the administration of three adjuvant chemotherapy regimens (gemcitabine + capecitabine [GX], gemcitabine + cisplatin [GP], and capecitabine monotherapy [X]). Finally, the safety of adjuvant chemotherapy was evaluated based on the incidence of grade 1–4 adverse events. Results The median RFS was 18 months in the non-AC group and 25 months in the AC group. The median OS was 34 months in the non-AC group; however, it was not reached in the AC group. The OS of the AC group was significantly higher than that of the non-AC group (P = 0.005). Multivariate Cox analysis demonstrated that nerve invasion (P = 0.001), preoperative elevation of cancer antigen 19–9 (CA 19–9) levels (P = 0.009), and postoperative adjuvant chemotherapy (P = 0.009) were independent prognostic factors for early-stage ICC after radical resection. The OS rates of the GX, GP, X, and non-AC groups were significantly different (P = 0.023) and were higher in the GX group than in the non-AC group (P = 0.0052). Among patients with elevated preoperative CA 19–9 levels, the OS rate was higher in the AC group than in the non-AC group (P = 0.022). In terms of safety, the incidence of grade 3 or 4 adverse reactions was Conclusion Adjuvant chemotherapy can prolong OS among patients with early-stage ICC who have undergone radical resection. Preoperative elevation of CA 19–9 levels and nerve invasion are independent prognostic factors for poor survival outcomes for early-stage ICC after radical resection. All chemotherapy regimens used in the study are safe.

The efficiency of reactive oxygen species (ROS)-mediated cancer therapy is restrained by intrinsic characteristics in the tumor microenvironment (TME), such as overexpressed glutathione (GSH), hypoxia and limited efficiency of H

A sharp increase in migrant workers has raised concerns for TB epidemics, yet optimal TB control strategies remain unclear in Taiwan regions. This study assessed intervention efforts on reducing tuberculosis (TB) infection among migrant workers. We performed large-scale data analyses and used them to develop a control-based migrant worker-associated susceptible–latently infected–infectious–recovered (SLTR) model. We used the SLTR model to assess potential intervention strategies such as social distancing, early screening, and directly observed treatment, short-course (DOTS) for TB transmission among migrant workers and locals in three major hotspot cities from 2018 to 2023. We showed that social distancing was the best single strategy, while the best dual measure was social distancing coupled with early screening. However, the effectiveness of the triple strategy was marginally (1–3%) better than that of the dual measure. Our study provides a mechanistic framework to facilitate understanding of TB transmission dynamics between locals and migrant workers and to recommend better prevention strategies in anticipation of achieving WHO’s milestones by the next decade. Our work has implications for migrant worker-associated TB infection prevention on a global scale and provides a knowledge base for exploring how outcomes can be best implemented by alternative control measure approaches.

Urolithiasis is one of the most common diseases in urology, with a lifetime prevalence of 14% and is more prevalent in males compared to females. We designed to explore sex disparities in the Chinese population to provide evidence for prevention measures and mechanisms of stone formation.A total of 98232 Chinese individuals who had undergone a comprehensive examination in 2017 were included. Fully adjusted odds ratios for kidney stones were measured using restricted cubic splines. Multiple imputations was applied for missing values. Propensity score matching was utilised for sensitivity analysis.Among the 98232 included participants, 42762 participants (43.53%) were females and 55470 participants (56.47%) were males. Patients' factors might cast an influence on the development of kidney stone disease distinctly between the two genders. A risk factor for one gender might have no effect on the other gender. The risk for urolithiasis in females continuously rises as ageing, while for males the risk presents a trend to ascend until the age of around 53 and then descend.Patients' factors might influence the development of kidney stones distinctly between the two genders. As age grew, the risk to develop kidney stones in females continuously ascended, while the risk in males presented a trend to ascend and then descend, which was presumably related to the weakening of the androgen signals.Key messagesWe found that patients' factors might cast an influence on the development of kidney stone disease distinctly between the two sexes.The association between age and urolithiasis presents distinct trends in the two sexesThe results will provide evidence to explore the mechanisms underlying such differences can cast light on potential therapeutic targets and promote the development of tailored therapy strategies in prospect.

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

There is a lack of evidence about the relationship between microorganisms and non‐carious cervical lesions (NCCLs) due to limited technologies. A group of 78 patients was enrolled for microbial 16S rRNA sequencing of dental plaques on normal and defective cervical surfaces. Parallel data from 39 patients were analysed with paired t tests, and Fusobacteriales exhibited significantly less distribution on NCCLs than on normal surfaces. As a result, Fusobacterium nucleatum, the most common oral bacterial strain belonging to the order Fusobacteriales, was selected for further research. From a scanning electron microscopy (SEM) scan, the tooth surface with Fusobacterium nucleatum and Streptococcus mutans culture was more intact than that without Fusobacterium nucleatum. Furthermore, the calcium contents in groups with Fusobacterium nucleatum were significantly higher than that without it. In further mechanistic research, Fusobacterium nucleatum was demonstrated to adhere to and disturb other organisms as well as producing alkaline secretions to neutralize the deleterious acidic environment, protecting the tooth structure. In conclusion, microorganisms and NCCLs were confirmed directly related through adherent bacterial interactions and pH regulation. The research provides a new perspective and experimental evidence for the relation between microorganisms and NCCLs, which guides clinical treatment and preventive dentistry in the future.

Dizhou Zhao, Jieyu Fang, Wei Xiong, Jun Lin, Wanmei Chen, Chujun Wu Department of Anesthesia, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jieyu FangDepartment of Anesthesia, The First Affiliated Hospital of Sun Yat-Sen University, No. 56 Zhongshan Road II, Guangzhou, People’s Republic of ChinaTel + 86-13660121136Email fangjy@mail.sysu.edu.cnBackground: Sugammadex has been a revolutionary reversal of neuromuscular blockade. It is known to be highly efficient. However, a change in the coagulation profile is one of the most dangerous potential complications which is a concern for both surgeon and anesthetist. Bleeding may cause hypovolemic shock, hematoma, and so on. To investigate the effects of sugammadex on coagulation profiles in patients with thyroidectomy, we compared patients that were treated with either sugammadex or neostigmine.Patients and Methods: Eighty patients with thyroid neoplasms undergoing thyroidectomy were randomly allocated to sugammadex group (group S) or neostigmine group (group N). Induction of anesthesia was preformed using propofol, sufentanil, and rocuronium. Group S received sugammadex 2.0mg/kg after trachea intubation, similarly Group N received neostigmine 40 μg/kg, for reversal of rocuronium-induced neuromuscular blockade. The intraoperative coagulation profiles were monitored after the rocuronium injection (T0), 10 minutes after reversal (T1) and 30 minutes after reversal (T2) by testing activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), and TEG-Haemonetics. Amount of bleeding was recorded during perioperative period.Results: There was no significant difference in the thromboelastogram, APTT, PT, FIB, or TT measurements at each time point in Group N. The reaction time (R time) and kinetics time (K time) of Group S in T1 were significantly longer than the corresponding times at T0 and T2, and the R times were significantly longer than those in Group N at the same time points (P< 0.05). Additionally, in Group S, the APTT was prolonged in T1 and returned to normal in T2.Conclusion: The result showed that sugammadex provided transient efficacy in prolonging the coagulation parameters, while neostigmine did not change the coagulation profile.Keywords: sugammadex, neostigmine, TEG-Haemonetics, coagulation, thyroidectomy

In situ self-assembly has attracted increasing research interest for applications in imaging and therapy in recent years. Particularly for protease-activated developments, inspiration is drawn from the innate specificity of their catalytic activities, rapid discovery of the various roles they play in the proliferation of certain diseases, and inherent susceptibility of small molecule peptide conjugates to proteolytic digestion in vivo. The overexpression of a disease-related protease of interest can be exploited as an endogenous stimulus for site-specific self-assembly to largely amplify a molecular event happening at the cellular level. This holds great potential for applications in early stage disease detection, long-term disease monitoring, and sustained therapeutic effects. This review summarizes the recent developments in protease-activated self-assemblies for imaging and therapeutic applications toward the manifestation of tumors, bacterial infections, neurodegenerative disorders, and wound recovery.