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Abstract Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs’ secretion. Metformin significantly increased EVs’ yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs’ therapeutic potential on periodontitis.

Abstract Background Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. Methods Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. Results The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. Conclusions MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Abstract Background This study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age. Methods Case records of patients aged

BackgroundSeveral studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer.MethodsThe PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs).ResultsFourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively.ConclusionIn cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

Abstract Objectives The objective of this systematic review and meta-analysis was to evaluate the effect of chewing gum on orthodontic pain and to determine the rate of bracket breakage associated with fixed orthodontic appliances. Methods This review and its reporting were performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Six electronic databases were searched up to March 16, 2023, to identify relevant studies that met the inclusion and exclusion criteria. Furthermore, grey literature resources were searched. The Cochrane Collaboration Risk of Bias tool 2 was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan, and sensitivity analysis and publication bias analysis were performed using STATA software. GRADE tool was used to evaluate the certainty of evidence. Results Fifteen studies with 2116 participants were ultimately included in this review, and 14 studies were included in the meta-analysis. Compared with the blank group, chewing gum had a significant pain relieving effect at all times after fixation of the initial archwire (P ≤ 0.05). No significant difference was found between the chewing gum group and the analgesics group at any timepoints (P > 0.05). Only four studies evaluated the rate of bracket breakage and revealed that chewing gum did not increase the rate of bracket breakage. The sensitivity analysis showed that there was no significant difference in the pooled outcomes after the included studies were removed one at times, and Egger analysis revealed no significant publication bias in included studies (P > 0.05). Conclusions Chewing gum is a non-invasive, low-cost and convenient method that has a significant effect on relieving orthodontic pain and has no effect on the rate of bracket breakage. Therefore, chewing gum can be recommended as a suitable substitute for analgesics to reduce orthodontic pain.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multi-system and multi-organ dysfunction, and is easily misdiagnosed early in the disease course. We aimed to accurately predict early SLE nomogram to provide a reference basis for the early clinical diagnosis of SLE. Methods: We retrospectively analyzed 167 patients who were first diagnosed with SLE at Fengxian District Central Hospital, Shanghai, between March 2017 and October 2022. Three groups of 129 physically healthy subjects, 67 patients with rheumatoid arthritis, and 40 patients with rashes were selected as controls during the same period. Patients with SLE and control group were randomly divided into training (n = 217) and validation (n = 141) group. Univariate and multivariate analyses were used to identify independent risk factors for early SLE diagnosis. The independent risk factors for diagnosis were used to construct a nomogram to predict early SLE. Results: Based on the training group, three variables were identified as independently influencing early SLE: platelets (odds ratio OR = 0.993, P = 0.047), albumin (OR = 0.833, P = 0.007), and complement component 1q (OR = 0.956, P = 0.000). The precision of the nomogram was assessed using C-index values and calibration plot diagrams. The C-index values were 0.929 for training group and 0.898 for validation group. Both the training group and validation group calibration curves showed good predicted outcomes. Conclusion: The construction of a nomogram can accurately predict the risk of early SLE. The model showed good discriminatory power and calibration for use in the diagnosis of SLE, providing a visual tool and reference basis for the early diagnosis of SLE.

Purpose To investigate the safety, efficacy, and the immune responses of focused ultrasound in cervical intraepithelial neoplasia (CIN).Methods Patients with biopsy-confirmed CIN were recruited for focused ultrasound treatment and asked to return during 3–6 and 6–12 months post-treatment to receive cervical cytology, high-risk human papilloma virus (HPV) detection, and colposcopy. The effective rate was evaluated within 3–6 months, whereas the recurrence rate was evaluated within 6–12 months. Cervicovaginal lavage and cervical tissue were sampled before and 3–6 months after treatment. The expression of interferon gamma (IFN-γ), endoplasmic reticulum aminopeptidase 1 (ERAP1), human leucocyte antigen I (HLA-I), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8) in the cervical tissue were observed by immunohistochemistry. Immunoglobulin A (IgA) and interleukin 10 (IL-10) levels in the cervicovaginal lavage were detected by enzyme-linked immunosorbent assay. Comparisons were made in immune analyte levels before and after treatment.Results We analyzed the results of 154 patients. The effective rate at 3–6 months was 96.8%. The recurrence rate at 6–12 months was 2.0%. The eradication rate of HPV was 72.4% at 3–6 months and 81.0% at 6–12 months. No serious adverse reactions and complications were observed. After treatment, a higher expression of ERAP1 was observed (p 0.05).Conclusions Focused ultrasound is an effective and safe therapy for treating CIN, which could improve the local immune milieu of the cervix to some extent.

Purpose To compare the efficacy and safety of focused ultrasound (FUS) therapy and cryotherapy for cervical squamous intraepithelial lesion (SIL).Methods In this retrospective study, data pertaining to women treated for cervical SIL with FUS therapy or cryotherapy at the Second Affiliated Hospital of Chongqing Medical University between 21 April 2018 and 31 August 2020 were obtained. The patients were followed up after 3–6 and 6–12 months. The proportions of women with no evidence of disease, recurrent disease, clearance of the human papillomavirus (HPV) and adverse effects or complications were determined.Results Of the 250 women with complete data who were included in the study, 144 and 106 received FUS therapy and cryotherapy, respectively. Overall, FUS therapy was observed to be more effective than cryotherapy (91.7 vs. 79.2%, p = 0.005). Statistically significant differences were noted in the treatment efficacy for patients with low-grade SIL (LSIL) (92.3 vs. 80.2%, p = 0.011). However, there were no significant differences in the treatment efficacy for patients with high-grade SIL (HSIL) (88.9 vs. 75.0%, p = 0.390). The recurrence rates in patients with LSIL treated with FUS therapy or cryotherapy showed no significant differences at the 6–12-month follow-up (1.0 vs. 6.0%, p = 0.163). Furthermore, there was no recurrence in patients with HSIL, either in the FUS or cryotherapy group. FUS therapy and cryotherapy resulted in similar HPV clearance at the 3–6-month follow-up (77.1 vs. 64.8%, p = 0.057). No statistically significant differences were observed in the complication rates between the two groups (3.5 vs. 1.9%, p = 0.717).Conclusion The results of this study suggest that FUS therapy is superior to cryotherapy in the treatment of cervical LSIL.

BackgroundRectal squamous cell carcinoma (RSCC) is a rare malignancy of the rectal tumor. Due to its extremely low incidence, there is still a lack of high-level treatment evidence and clinical consensus on this disease.Case reportIn this article, we report a treatment process of RSCC with high PD-L1 expression. Firstly, this patient received 2 cycles of Pembrolizumab immunotherapy, but the efficacy was less sanguine. Subsequently, 4 cycles of mFOLFOX6 chemotherapy were synchronously performed on the basis of the initial regimen. Although partial remission was achieved in the lymph nodes thereafter, the changes in the primary lesions were still not significant. After that, the patient received radiotherapy, and followed by 6 cycles of PC (Albumin-binding Paclitaxel and Nedaplatin) regimen chemotherapy combined with Pembrolizumab. Eventually, the patient achieved no evidence of disease (NED) status, and no signs of recurrence or metastasis were found after 12 months of follow-up.ConclusionThis is the first report of a RSCC patient with high PD-L1 expression achieving a complete response. Looking back over the whole treatment process of this patient, we found that the participation of radiotherapy was the inflection point of prominent efficacy, which may provide a new idea for the selection of comprehensive treatment strategies for patients with RSCC.

PurposeTo investigate the clinical factors affecting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).MethodsClinical data of 124 LARC patients treated with nCRT and surgery in the fourth Hospital of Hebei Medical University from 2014 to 2019 were retrospectively analyzed. In this study, univariate analysis and logistic dichotomous multivariate regression analysis were used to study the clinical factors affecting pCR, and the receiver operator characteristic curve (ROC) analysis was used to further verify the accuracy of partial indexes in predicting pCR.ResultsOf the 124 enrolled patients, 19 patients (15.32%) achieved pCR. Univariate analysis showed that the number of cycles of consolidation chemotherapy, serum carcino-embryonic antigen (CEA) level before treatment, MRI longitudinal length of tumor, and extramural vascular invasion (EMVI) were statistically correlated with pCR. ROC analysis of the longitudinal length of tumor measured by MRI showed that the area under the curve (AUC) value, sensitivity and specificity were 0.735, 89.47% and 48.57% respectively, and the optimal cut-off value was 5.5cm. The ROC analysis showed that the AUC value, sensitivity and specificity of pCR prediction using CEA were 0.741, 63.16% and 90.48%, respectively, and the optimal cut-off value was 3.1ng/ml. Multivariate results showed that the number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI were independent predictors of pCR.ConclusionThe number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI may be important determinants of LARC patients to reach pCR after nCRT.

Abstract Purpose A previous study demonstrated that intracranial tumor volume had some correlation with gastrointestinal cancer patients' outcome. The aim of this study was to analyze patients with esophageal carcinoma (EC) and brain metastases to investigate if intracranial tumor volume would be a predictor of these patients' survival. Methods A total of 52 patients with brain metastases from esophageal squamous cell carcinoma or esophageal adenocarcinoma were retrospectively reviewed. Patients without images of brain metastases in the hospital information system were eliminated. Results The median follow‐up time duration was 8.4 months (interquartile range 4.0–15.2). The median overall survival (OS) from time of brain metastases diagnosis was 8.0 months for all cases. Median OS of patients with small and large cumulative intracranial tumor volume (CITV) (

IntroductionTo evaluate the predictive value of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).MethodsFrom January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT scans within 1 week before and 8-9 weeks after nCRT, were enrolled in this study according to a pre-designed screening criteria. After total mesorectal excision (TME) surgery, we assessed tumor response to treatment and analyzed the correlation between imaging parameters obtained from two PET-CT scans and tumor regression status.ResultsTumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rs= -0.58 and 0.59, respectively), and also had a strong correlation with GR (rs = -0.7 and 0.63, respectively). Further ROC analysis showed that post-SUVmax and RI had higher values in predicting whether patients could achieve GR and pCR after nCRT, and the area under the curve (AUC) of both were greater than 0.9. The positive predictive values (PPVs) and negative predictive values (NPVs) of post-SUVmax for GR were 80.01% and 97.3%, and for pCR were 66.68% and 97.5%, respectively. The PPVs and NPVs of the RI values for GR were 84.61% and 94.87%, and for pCR were 69.24% and 100%, respectively.ConclusionFor LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of 18F-FDG uptake capacity of tumor tissues before and after nCRT, is of great value for predicting the response of patients to neoadjuvant therapy and guiding the selection of subsequent treatment strategies.

Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively. Blocking the glycosylation of the B7 family members PD-L1, PD-L2, B7-H3, and B7-H4 inhibited the self-stability and receptor binding of these immune checkpoint proteins, leading to immunosuppression and rapid tumor progression. Therefore, regulation of glycosylation may be the “golden key” to relieve tumor immunosuppression. The exploration of a more precise glycosylation regulation mechanism and glycan structure of B7 family proteins is conducive to the discovery and clinical application of antibodies and small molecule inhibitors.

Abstract Background Brain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice. Methods A total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan–Meier method and Cox proportional hazards models. Results The median time from diagnosis of EC to BM was 11.8 months (0–249.2 months). The median overall survival (OS) was 4.8 months (1.13–23.3 months), with 20% of patients achieving the 1‐year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score

Integrons can capture and express foreign gene cassettes through site-specific recombination and are important genetic elements in spreading antibiotic resistance genes among bacteria. We have developed a two-dimensional PCR technology (2D-PCR) based on the base quenching probe technology in detecting three major integrons at the same time. The minimum detection limits were evaluated by detecting three plasmids each harboring different types of integron with different concentrations. The specificity of this method was evaluated by screening and typing three major types of integrons in 105 clinical Proteus isolates, and the results were compared with those of traditional PCR. Results indicated that the melting temperature (Tm) difference of the three genes was about 10 °C and was very easy to be distinguished. The minimum detection limits of intI1, intI2 and intI3 were all below 102 copies/μl. The detection results of clinical isolates were consistent with those of traditional PCR. This developed rapid, economic and high-throughput 2D-PCR based method can detect three main classes of integron at the same reaction, and can be applied to clinical isolates in large-scale integron screening and typing.

The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

BackgroundBrain metastases are the most common cause of intracranial malignancy, often resulting in significant morbidity and mortality. Brain metastases from esophageal squamous cell carcinoma (ESCC) are relatively rare, with a rate of generally less than 2%.Case ReportIn this article, we report a rare case of ESCC with asymptomatic brain metastasis. The combined positive score (CPS) of programmed cell death-ligand 1 (PD-L1) from the primary tumor was 2 by DAKO 22C3 and 3 by VENTANA SP263. The proportion of tumor infiltrating lymphocytes (TILs) was 1%. After receiving 15 cycles of immune checkpoint inhibitors (ICIs), the patient’s brain metastatic lesion had disappeared and was replaced by a local necrotic area. He retains good cognitive function with a stable disease at the primary site.ConclusionsThis is the first to be reported in an ESCC patient whose brain metastatic lesion had a complete response to ICIs, which may provide supporting data for using ICIs as an option of treatment for ESCC patients with brain metastases.

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC).Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method.Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05).Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.

BackgroundConcurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal carcinoma patients who are not surgical candidates. The efficacy of induction chemotherapy (IC) or consolidation chemotherapy (CCT) for unresectable esophageal cancer (EC) treated with CCRT is unclear. We performed a systematic review and meta-analysis of published papers to evaluate the potential benefit of IC or CCT for patients with EC.MethodsEligible studies of IC followed by CCRT (IC-CCRT) vs. CCRT alone or CCRT followed by CCT (CCRT-CCT) vs. CCRT alone were retrieved through extensive searches of the PubMed, Science Direct, Embase, and Cochrane Library databases from the establishment of the database to July 31, 2021. Data such as 1-, 2-, 3-, and 5-year overall survival (OS), local recurrence rate (LRR), and distant metastasis rate (DMR) were collected for meta-analysis to evaluate the efficacy of IC/CCT.ResultsFour studies of IC-CCRT vs. CCRT including 836 EC patients and six studies of CCRT-CCT vs. CCRT including 1,339 patients with esophageal squamous cell carcinoma (ESCC) were finally identified in our analysis. Both IC-CCRT group [hazard ratio (HR) 0.446, 95% CI 0.286–0.693; p < 0.001] and CCRT-CCT group (HR 0.542, 95% CI 0.410–0.716; p < 0.001) exhibited statistically significant improvement in 1-year OS rate compared to that of CCRT, while the 2-year OS rate of IC-CCRT (HR 0.803, 95% CI 0.589–1.095; p = 0.166) or CCRT-CCT (HR 0.783, 95% CI 0.600–1.022; p = 0.072) was similar with that of CCRT. And the 3-year OS rate between IC-CCRT and CCRT was similar (HR 1.065, 95% CI 0.789–1.439; p = 0.680). However, comparing with CCRT alone, the CCRT-CCT group had lower DMR [odds ratio (OR) 1.562, 95% CI 1.090–2.240; p = 0.015] and higher 3-year OS rate (HR 0.786, 95% CI 0.625–0.987; p = 0.039). Besides, no differences were observed between the CCRT-CCT and CCRT groups in 5-year OS rate (HR 0.923, 95% CI 0.706–1.205; p = 0.555) and LRR (OR 0.899, 95% CI 0.686–1.179; p = 0.441).ConclusionThe study revealed the short-time survival benefit of additional IC or CCT compared to CCRT alone for patients with unresectable EC, and CCRT followed by CCT could significantly reduce the risk of distant metastases.

Objective: This study aims to examine the clinical characteristics of patients with brain metastases (BM) from small-cell esophageal carcinoma (SCEC) and to explore the association of the corresponding factors with overall survival (OS).Methods: The data of 18 patients with brain metastases from SCEC, diagnosed from January 1, 2006, to December 31, 2018, in the Fourth Hospital of Hebei Medical University were analyzed retrospectively.Results: The 18 patients who were included in this study accounted for 6.7% of the patients with SCEC diagnosed from 2006 to 2018. Of the 18 patients, 8 (44.4%) were females. For the entire cohort, the median OS was 7 months, the 1-year OS was 22.2%, and the 2-year OS was 0%. For patients who received whole-brain radiotherapy (WBRT) and for those who did not (13 vs. 5), the median OS was 11.9 and 3 months, respectively, and the 1-year OS was 30.8 and 0%, respectively. When comparing diagnosis-specific Graded Prognostic Assessment (DS-GPA) scores of patients with BM from SCEC ranging from 2.5 to 4 and from 0 to 2, the median OS was 13.1 and 4 months, respectively, and the 1-year OS was 57.1 and 0%, respectively. In the univariable regression, patients who received WBRT had improved OS compared to those who did not (HR = 0.249, p = 0.018), and patients with a DS-GPA score of 2.5–4 were associated with improved OS compared with patients with a DS-GPA score of 0–2 (HR = 0.050, p = 0.005).Conclusion: The incidence of brain metastases in patients with SCEC is low, but the prognosis in those patients is very poor. The DS-GPA score may be a prognostic factor of patients with BM from SCEC. Brain radiotherapy could improve the survival of these patients.

PurposeDue to the low incidence of intracranial disease among patients with esophageal cancer (EC), optimal management for these patients has not been established. The aim of this real-world study is to describe the clinical characteristics, treatment approaches, and outcomes for esophageal squamous cell carcinoma (ESCC) patients with brain metastases in order to provide a reference for treatment and associated outcomes of these patients.MethodsPatients with ESCC treated at the Fourth Hospital of Hebei Medical University between January 1, 2009 and May 31,2020 were identified in an institutional tumor registry. Patients with brain metastases were included for further analysis and categorized by treatment received. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models.ResultsAmong 19,225 patients with ESCC, 66 (0.34%) were diagnosed with brain metastases. Five patients were treated with surgery, 40 patients were treated with radiotherapy, 10 with systemic therapy alone, and 15 with supportive care alone. The median follow-up time was 7.3 months (95% CI 7.4-11.4). At last follow-up, 59 patients are deceased and 7 patients are alive. Median overall survival (OS) from time of brain metastases diagnosis was 7.6 months (95% CI 5.3-9.9) for all cases. For patients who received locoregional treatment, median OS was 10.9 months (95% CI 7.4-14.3), and survival rates at 6 and 12 months were 75.6% and 37.2%, respectively. For patients without locoregional treatment, median OS was 3.0 months (95% CI 2.5-3.5), and survival rates at 6 and 12 months were 32% and 24%, respectively. OS was significantly improved for patients who received locoregional treatment compared to those treated with systematic treatment alone or supportive care (HR: 2.761, 95% CI 1.509-5.053, P=0.001). The median OS of patients with graded prognostic assessment (GPA) score 0-2 was 6.4 months, compared to median OS of 12.3 months for patients with GPA >2 (HR: 0.507, 95% CI 0.283-0.911).ConclusionBrain metastases are rare in patients with ESCC. GPA score maybe a useful prognostic tool for ESCC patients with brain metastases. Receipt of locoregional treatment including brain surgery and radiotherapy was associated with improved survival.

Vulvar lichen sclerosus (VLS) is a common inflammatory condition associated with an increased risk of developing vulvar carcinoma. Recently, high-intensity focused ultrasound (HIFU) has been identified as a promising treatment modality for VLS in several clinical trials. However, in HIFU therapy, therapeutic outcome is routinely assessed visually by an expert using standardized grading criteria. Furthermore, such a therapeutic assessment cannot be made until at least 3 months after treatment. Therefore, an objective and timely method capable of quantitatively evaluating HIFU treatment effectiveness is desired, which may help identify patients whose treatment is insufficient promptly and prevent delay in re-treatment. The purpose of this study is to investigate the feasibility of using active dynamic thermal imaging (ADT) and hyperspectral imaging (HSI) as two individual objective and non-invasive optical methods for prompt quantitative assessment of the therapeutic response to HIFU treatment in VLS. From December 2018 to March 2019, 20 female VLS patients who underwent HIFU treatment were evaluated using both the ADT and HSI methods. The effective damage rate from the ADT method and the entropy of feature index from the HSI method were used to develop a multivariate linear discriminant classification model for grading the effectiveness of HIFU treatment in comparison with clinical evaluation gold standard. It was found that ADT was able to correctly differentiate ineffective treatments from effective ones with a sensitivity of 100% and specificity of 100%, while the sensitivity and specificity of HSI were 75 and 87.5%, respectively. The classification results demonstrate the clinical potential of the ADT and HSI methods for timely non-invasive and quantitative assessment of HIFU treatment for VLS.

Chemotherapy and photo-sonodynamic therapy (PSDT) can be combined through drug delivery nano-platforms to enhance the anti-tumor efficacy, however, which is limited by hypoxia in tumor, thereby causing chemotherapy resistance. Perfluoropentane (PFP) has the ability to carry oxygen and to enhance ultrasound or photoacoustic imaging after vaporization. Herein, we constructed a kind of nanoparticles (PTX/ICG and oxygen loaded PLGA nanoparticles (PIO_NPs)), which had PFP core carrying oxygen and PLGA shell loaded indocyanine green (ICG) and paclitaxel (PTX). PIO_NPs harbored good optical stability and the ability to transit phase. Moreover, it could rapidly release PTX and generate ROS under the mediation by near-infrared laser and low-intensity ultrasound. The PIO_NPs enhanced contrast of the ultrasound and PA imaging. In particular, PIO_NPs may be used to monitor and guide treatment for the accumulation of PIO_NPs at tumor site can be observed by PA imaging. Compared with PTX or other nanoparticles, PIO_NPs combined with laser and ultrasound (L.U) significantly induced apoptosis of SKOV3 cells and inhibited SKOV3 tumor growth. Therefore, PIO_NPs are of great potential in cancer imaging and therapy.

ObjectivesTo describe the molecular characteristics of beta-lactamases in bloodstream-infection Escherichia coli isolated from elderly patients, and to determine the genotypic patterns of blaCMY–2 and blaADC–162.MethodsA total of 50 bloodstream-infection E. coli isolates were obtained from patients aged > 50 years at Shanghai Sixth People’s Hospital South Campus during 2015–2018. The isolates were subjected to beta-lactamase detection using phenotypic and molecular methods. Beta-lactamase genes were verified by sequencing and the phylogenetic relationships of the isolates were analyzed by multilocus sequence typing (MLST). The transferability of plasmids carrying blaCMY–2 and blaADC–162 genes was verified by conjugation experiments and plasmid replicon typing.ResultsEight beta-lactamase subtypes were detected in 50 isolates of bloodstream-infection E. coli. blaTEM–1 (21/50) was the most common beta-lactamase gene, followed by blaCTX–M–14 (8/50), blaOXA–27 (5/50), blaCTX–M–27 (3/50), blaCTX–M–65 (1/50), blaADC–162 (1/50), and blaCMY–2 (1/50). Of these, blaADC–162 (ST95-A), and blaCMY–2 (ST95-B2) have not previously been reported in bloodstream-infection E. coli. In 21 isolates, beta-lactamase genes were located on conjugative plasmids belonging to incompatibility groups FrepB (n = 7), FIA (n = 1), FIC (n = 2), K (n = 8), N (n = 1), and I (n = 1), and blaCTX–M was associated with the common elements ISEcp1, IS903, and IS26, but with special sequences (region V, region Y, and region W) for ISEcp1 in 14 isolates.ConclusionTo the best of our knowledge, this study provides the first molecular characterization of beta-lactamase genes in E. coli isolated from the bloodstream in elderly patients. Beta-lactamase genes were detected at a relatively high frequency in elderly patients with bloodstream E. coli infections. Plasmid replicon analysis showed that horizontal dissemination of beta-lactamase genes was mainly mediated by IncK and IncF plasmids, which could encode multidrug resistance genes. The study also provides the first report of ISAba1-blaADC–162-tnpA and ISEcp1-blaCTX–M–14-IS903-blaCMY–2-blc-sugE in E. coli, and demonstrates IncF plasmid-mediated blaADC–162 and blaCMY–2 gene dissemination among bacteria.

ObjectiveTo describe the polymorphisms of gene cassette promoters of the class 1 integron in clinical Proteus isolates and their relationship with antibiotic resistance.MethodsPolymorphisms of the gene cassette promoter in 153 strains of Proteus were analyzed by PCR and nucleotide sequencing. Variable regions of atypical class 1 integrons were detected by inverse PCR and nucleotide sequencing. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used to analyze the phylogenetic relationships of class 1 integron-positive clinical Proteus isolates. Representative beta-lactamase genes (bla), including blaTEM,blaSHV,blaCTX-M-1,blaCTX-M-2,blaCTX-M-8,blaCTX-M-9,blaCTX-M-25 and blaOXA-1, and plasmid-mediated quinolone resistance (PMQR) genes including qnrA, qnrB, qnrC, qnrD, qnrS, oqxA, oqxB, qepA, and aac(6′)-Ib were also screened using PCR and sequence analysis.ResultsFifteen different gene cassette arrays and 20 different gene cassettes were detected in integron-positive strains. Of them, aadB-aadA2 (37/96) was the most common gene cassette array. Two of these gene cassette arrays (estX-psp-aadA2-cmlA1, estX-psp-aadA2-cmlA1-aadA1a-qacI-tnpA-sul3) have not previously been reported. Three different Pc-P2 variants (PcS, PcWTGN-10, PcH1) were detected among the 96 Proteus strains, with PcH1 being the most common (49/96). Strains carrying the promoters PcS or PcWTGN-10 were more resistant to sulfamethoxazole, gentamicin and tobramycin than those carrying PcH1. Strains with weak promoter (PcH1) harbored significantly more intra- and extra-integron antibiotic resistance genes than isolates with strong promoter (PcWTGN-10). Further, among 153 isolates, representative beta-lactamase genes were detected in 70 isolates (blaTEM-1, 54; blaOXA-1, 40; blaCTX-M-3, 12; blaCTX-M-14, 12; blaCTX-M-65, 5; blaCTX-M-15, 2) and representative PMQR genes were detected in 87 isolates (qnrA, 6; qnrB, 3; qnrC, 5; qnrD, 46; qnrS, 5; oqxA, 7; aac(6′)-Ib, 13; aac(6′)-Ib-cr, 32).ConclusionTo the best of our knowledge, this study provides the first evidence for polymorphisms of the class 1 integron variable promoter in clinical Proteus isolates, which generally contain relatively strong promoters. Resistance genotypes showed a higher coincidence rate with the drug-resistant phenotype in strong-promoter-containing strains, resulting in an ability to confer strong resistance to antibiotics among host bacteria and a relatively limited ability to capture gene cassettes. Moreover, strains with relatively weak integron promoters can “afford” a heavier “extra-integron antibiotic resistance gene load”. Furthermore, the gene cassettes estX, psp and the gene cassette arrays estX-psp-aadA2-cmlA1, estX-psp-aadA2-cmlA1-aadA1a-qacI-tnpA-sul3 have been confirmed for the first time in clinical Proteus isolates. Beta-lactamase genes and PMQR were investigated, and blaTEM-1 and blaOXA-1 were the most common, with qnrD and aac (6′)-Ib-cr also being dominant.

To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p

The Southwest China Karst, the largest continuous karst zone in the world, has suffered serious rock desertification due to the large population pressure in the area. Recent trend analyses have indicated general greening trends in this region. The region has experienced mild climate change, and yet significant land use changes, such as afforestation and reforestation. In addition, out-migration has occurred. Whether climate change or human-induced factors, i.e., ecological afforestation projects and out-migration have primarily promoted forest restoration in this region was investigated in this study, using Guizhou Province as the study area. Based on Moderate-Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) data, we found general greening trends of the forest from 2000 to 2010. About 89% of the forests have experienced an increase in the annual NDVI, and among which, about 41% is statistically significant. For the summer season, more than 65% of the forests have increases in summer NDVI, and about 16% of the increases are significant. The strongest greening trends mainly occurred in the karst areas. Meanwhile, annual average and summer average temperature in this region have increased and the precipitation in most of the region has decreased, although most of these changes were not statistically significant (p > 0.1). A site-based regression analysis using 19 climate stations with minimum land use changes showed that a warming climate coupled with a decrease in precipitation explained some of the changes in the forest NDVI, but the results were not conclusive. The major changes were attributed to human-induced factors, especially in the karst areas. The implications of an ecological afforestation project and out-migration for forest restoration were also discussed, and the need for further investigations at the household level to better understand the out-migration–environment relationship was identified.

Introduction: To evaluate the predictive value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: From January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT scans within 1 week before and 8-9 weeks after nCRT, were enrolled in this study according to a pre-designed screening criteria. After total mesorectal excision (TME) surgery, we assessed tumor response to treatment and analyzed the correlation between imaging parameters obtained from two PET-CT scans and tumor regression status. Results: Tumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rs= -0.58 and 0.59, respectively), and also had a strong correlation with GR (rs = -0.7 and 0.63, respectively). Further ROC analysis showed that post-SUVmax and RI had higher values in predicting whether patients could achieve GR and pCR after nCRT, and the area under the curve (AUC) of both were greater than 0.9. The positive predictive values (PPVs) and negative predictive values (NPVs) of post-SUVmax for GR were 80.01% and 97.3%, and for pCR were 66.68% and 97.5%, respectively. The PPVs and NPVs of the RI values for GR were 84.61% and 94.87%, and for pCR were 69.24% and 100%, respectively. Conclusion: For LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of 18F-FDG uptake capacity of tumor tissues before and after nCRT, is of great value for predicting the response of patients to neoadjuvant therapy and guiding the selection of subsequent treatment strategies. [ABSTRACT FROM AUTHOR]