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Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and to detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs) and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture and different depths of whole genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor-informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor-identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21-47 tumor-identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay.

Childhood asthma has substantial effects on children's health. It is important to identify influencing factors in early life in the development of childhood asthma. We aim to evaluate the effects of early-life factors and indoor environmental exposure on childhood asthma in Chongqing, China.We designed a case-control study to enrol children with asthma aged 3 to 14 years old and controls in Chongqing, China. The "Children's Early Life and Indoor Environment Survey" was used to collect the early-life factors and indoor environmental exposure of foetuses in utero and of infants during the first 3 years of life. A multivariate logistic regression model was used to evaluate the association between independent variables and childhood asthma and the interaction of early-life factors and environmental exposure.A total of 160 asthma cases and 247 controls were included in this study. The mean ages of the cases and controls were 5.53 ± 1.88 and 5.72 ± 2.34 years, respectively (P = 0.192). Early-life factors and indoor environmental exposure were independently associated with childhood asthma. Infectious diseases of the respiratory system in children under 3 years old [adjusted odds ratio (OR) = 5.76, 95% confidence interval (CI) 2.49-13.30], bedroom air conditioner use (adjusted OR = 4.61, 95% CI 1.45-14.64), and bedroom dampness/mould (adjusted OR = 2.98, 95% CI 1.54-5.75) ranked as the three most significant exposures associated with the risk of childhood asthma. Other factors associated with an increased risk of childhood asthma included second-hand smoke exposure in early life (adjusted OR = 1.93, 95% CI 1.24-3.00), neonatal pneumonia (adjusted OR = 1.90, 95% CI 1.05-3.42) and maternal allergic diseases during pregnancy (adjusted OR = 2.13, 95% CI 1.10-4.10). The interaction effects of child second-hand smoke exposure with other covariates were not found to be statistically significant.Early-life factors and indoor environmental exposure are closely related to childhood asthma in Chongqing, China. Further interventions and management in the early life of children should be considered to prevent and control childhood asthma in Chongqing and similar cities.

The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.

To evaluate the efficacy of oblique lumbar interbody fusion combined with unilateral pedicle screw fixation via Wiltse approach in the treatment of lumbar spinal stenosis.From July 2017 to January 2019, 90 patients with lumbar spinal stenosis, including 38 males and 52 females, aged from 43 to 75 years old with an average of(59.9±8.8) years old, and were treated with oblique lumbar interbody fusion(OLIF) combined with Wiltse unilateral pedicle screw fixation. Surgical decompression and fixation was performed in 50 cases of single segment, 32 cases of double segments and 8 cases of three segments. The distribution of responsible segments included 8 cases of LAll patients were followed up from 12 to 33 months, with an average of (20.2±6.6) months. Mean operation time was (103.3±35.9) min, and mean intraoperative blood loss was (70.4±17.8) ml. VAS of low back pain leg pain, and ODI decreased from 6.2±1.1, 6.1±0.9 and (59.9±4.2)% to 2.7±0.5, 2.5±0.5 and (31.3±8.8)%. SF-36 scale significantly increased from (37.2±3.1) to (54.9±6.1) at the six months postoperation(OLIF combined with unilateral pedicle screw fixation via Wiltse approach is effective in treating lumbar spinal stenosis with minimally invasive advantages such as less trauma and less complications. Under the premise of strictly grasping the indications, this method could also achieve satisfactory clinical results in multi-segments oprations.

Background Breast cancer has become the most frequently diagnosed cancer worldwide. Increasing evidence indicated that zinc finger proteins (ZNFs), the largest family of transcription factors, contribute to cancer development and progression. Although ZNF384 is overexpressed in several types of human cancer, the role of ZNF384 in breast cancer remains unknown. Therefore, our research focused on ZNF384 regulation of the malignant phenotype of breast cancer and the underlying molecular mechanisms. Methods CCK-8 and colony formation assays were used to evaluate cell proliferation. Transwell and scratch assays were used to evaluate the cell migration and invasion. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were used to confirm the target relationship between ZNF384 and zinc finger E-box binding homeobox 1 (ZEB1). Xenografts were used to monitor the targets in vivo effects. Results We noted that ZNF384 was significantly overexpressed in breast cancer and highlighted the oncogenic mechanism of ZNF384. ZNF384 transactivated ZEB1 expression and induced an epithelial and mesenchymal-like phenotype, resulting in breast cancer metastasis. Furthermore, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. Together, we unveiled a feedback loop of ZNF384–ZEB1 in breast cancer metastasis. Conclusions The findings suggest that ZNF384 can serve as a prognostic factor and a therapeutic target for breast cancer patients.

Breast cancer remains the most common malignancy in females around the world. Recently, a growing number of studies have focused on gene dysregulation. In our previous study, Krüppel-like factors (KLFs) were found to play essential roles in breast cancer development, among which KLF2 could function as a tumor suppressor. Nevertheless, the underlying molecular mechanism remains unclear.miR-92a-3p was identified as the upstream regulator of KLF2 by starBase v.3.0. The regulation of KLF2 by miR-92a-3p was verified by a series of in vitro and in vivo assays. Further exploration revealed that Baculoviral IAP Repeat Containing 5 (BIRC5) was the target of KLF2. ChIP assay, dual-luciferase reporter analysis, quantitative real-time PCR, and western blot were performed for verification.miR-92a-3p functioned as a tumor promoter by inhibiting KLF2 by binding to its 3'-untranslated region (3'-UTR). In addition, KLF2 could transcriptionally suppress the expression of BIRC5.Collectively, our results uncovered the miR-92a-3p/KLF2/BIRC5 axis in breast cancer and provided a potential mechanism for breast cancer development, which may serve as promising strategies for breast cancer therapy.

Objective To compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger. Methods We retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels ( Results There were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles. Conclusion The IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary.

BackgroundThe GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified.MethodsThis was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols.ResultsAfter PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMIConclusionsThe suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients.

Background: Mental health disorders are highly prevalent in polycystic ovary syndrome (PCOS) cases. The etiology for anxiety/depression in women with PCOS still remains unclear, due to conflicting results. Aim: To examine whether an association exists between the mental health of Chinese women with PCOS and various indicators such as their disease characteristics, biochemistry results and sleep status. Methods: During July 2018 and January 2020, our study included a total of 433 women diagnosed with PCOS at Chongqing Hospital of Traditional Chinese Medicine. Sleep-related variables were evaluated by the Pittsburgh Sleep Quality Index (PSQI), anxiety and depression values were quantified by the Hospital Anxiety and Depression Scale (HADS), and biochemistry results were collected from the medical records of the patients. Results: 26.6% patients resulted as positive anxiety and 23.6% as positive depression. We found significant associations between anxiety/depression status and sleep conditions of PCOS patients. More specifically, anxiety significantly associated with sleep quality OR (95%CI) = 1.611 (1.147–2.261), sleep disturbance 2.326 (1.468–3.685) and daytime dysfunction 1.457 (1.122–1.891). Similarly, depression significantly associated with sleep quality 1.467 (1.043–2.063), sleep disturbance 1.624 (1.030–2.561) and daytime dysfunction 1.406 (1.077–1.836). There was no association detected between mental health and disease characteristics, as well as reproductive and metabolic indicators in PCOS. Limitation: Cross-sectional nature of the data prevents causal associations, selection bias of a hospital-based population. Conclusions: Sleep-related disorders might be involved in the etiology and development of the anxiety/depression observed in PCOS cases. We propose that management of sleep disorders should be an integral part of the disease management of women with PCOS.

To investigate the effect of internal external fixator assisted O-arm navigation imaging in the treatment of unstable pelvic fractures.From May 2019 to November 2019, 15 patients with unstable pelvic fractures were treated by intraoperative O-arm navigation imaging using INFIX technology. There were 6 males and 9 females. The age ranged from 24 to 66 years old. The course of disease ranged from 2 to 14 days. According to Tile classification, there were 1 case of B1 type, 8 cases of B2 type, 3 cases of C1 type, and 3 cases of C2 type. According to Young-Burgess classification, there were 8 cases of LC, 1 case of APC, 4 cases of VS, 2 cases of CM. Preoperative routine pelvic anteroposterior film, entrance position, exit position and pelvic CT three-dimensional reconstruction were performed. Intraoperative O-arm navigation system three-dimensional reconstruction and triplane scanning imaging were used to evaluate the effect of intraoperative reduction. The anterior pelvic ring was fixed with internal external fixator, and the posterior ring was fixed with sacroiliac screw, plate screw or lumbar iliac screw. The operation time, intraoperative bleeding and nail placement were observed and recorded. The quality of fracture reduction was evaluated by Matta standard, and the postoperative function was evaluated by Majeed function score.Wound healing was good in all patients without vascular, nerve and local irritation complications. All the 15 patients were followed up for 10 to 16 months. The fracture reduction was evaluated according to the Matta scoring standard, 9 cases were excellent results, 5 cases were good, and 1 case was medium. The Majeed functional score was 0 to 95 points.The built-in external fixator assisted O-arm navigation imaging system in the treatment of unstable pelvic fractures. The reduction effect is evaluated in advance, the operation time is shortened, and the accuracy of internal fixation is improved. The operation is simple, safe and less bleeding. The operation is in line with the principles of minimally invasive medical treatment and precision medical treatment in orthopedics, which is conducive to the recovery of patients' postoperative function and rapid recovery.

ObjectiveTo investigate the COVID-19 vaccination coverage rate and differences among various COVID-19 prevention primary healthcare (PHC) facilities in China and understand their attitudes towards COVID-19 vaccine. These findings are helpful to provide important suggestions to further improve national COVID-19 vaccination rate.DesignA nationwide cross-sectional online survey was designed and conducted among COVID-19 prevention and control management teams at PHC facilities in mainland China. In the self-designed questionnaires, each subject was asked to evaluate on a 1–10 scale (10=extremely important/acceptable/influential) the COVID-19 vaccination importance, acceptance and factors related to vaccine hesitancy.SettingSubjects from 31 provinces and autonomous regions including minorities across mainland China were invited to complete the questionnaire between 22 February 2021 and 2 March 2021.ParticipantsWere selected by multistage stratified sampling, 998 valid questionnaires (valid rate 99.11%) were collected. The respondents were divided into group A (≤5 respondents within each PHC facility, n1=718) and group B (>5 respondents within each PHC facility, n2=280).Outcome measuresSurvey on vaccination rate and attitude towards COVID-19 vaccine included the following: (1) if the subjects think the vaccination is important in containment of COVID-19 pandemic (1–10 scale, 10=extremely important), (2) if they would accept COVID-19 vaccine (1–10 scale, 10=extremely acceptable) and (3) their opinions on 7 factors possibly related to vaccine hesitancy (1–10 scale, 10=extremely influential). All the items were designed based on the previous expert interviews.ResultsOur results showed vaccination rate was greater in group A (85.93%) than in group B (66.43%) (pConclusionIn PHC facilities, although there was a higher COVID-19 vaccination rate among COVID-19 prevention and control teams, some subgroups with different descriptive characters showed negative attitudes towards COVID-19 vaccination. Because primary care workers in China are highly expected to receive the vaccination, and support and educate the public for COVID-19 vaccination. Thus, it is important and necessary to continue to educate them about their vaccination concerns and change their attitudes towards vaccination. Our findings are highly beneficial for designing public vaccination education strategies.

Background In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS. Methods A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors. Results After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight. Conclusion(s) In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.

To explore clinical effect of arthroscopic debridement combined with platelet-rich plasma (PRP) injection for Kellgren-Lawrence(K-L) gradeⅠ-Ⅲ knee osteoarthritis (KOA) .Totally 117 patients with KOA who underwent arthroscopic debridement combined with injection from November 2015 to January 2019 were retrospectively analyzed. According to different injection drugs, the patients were divided into sodium hyaluronate group(group A) and PRP group(group B). In group A, there were 60 patients, including 27 males and 33 females, aged from 49 to 67 years old with an average age of (54.1±4.8) years old;12 patients with gradeⅠ, 23 patients with gradeⅡand 25 patients with grade Ⅲ according to K-L clssification, 2 ml(20 g) sodium hyaluronate was injected into knee joint after intraoperative, 1, 2, 3 weeks after operation for 4 times. In group B, there were 57 patients, including 25 males and 32 females, aged from 47 to 70 years old with an average of (55.8±5.0) years old, 10 patients with gradeⅠ, 20 patients with gradeⅡand 27 patients with grade Ⅲ according to K-L classification, injected 5 ml PRP at the same time. Postoperative complications was recorded between two groups. Postoperative visual analogue scale(VAS) and Lysholm score at 3, 6, 12 months were used to evaluate improvement of knee pain and joint function.All patients were followed up for 12 to 19 months with an average of (14.1±1.6) months. There was no significant difference in postopertaive complications between group A and group B (Arthroscopic debridement combined with sodium hyaluronate or PRP injection for K-L gradeⅠ-Ⅲ KOA could effectively relieve pain and improve joint function with higher safety in short term, but the medium-long-term effect of PRP injection is stable.

Background Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non‐high‐incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. Methods We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40‐74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. Results Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C‐index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high‐risk and low‐risk group divided based on score from the nomogram predicted a significantly distinct detection rate. Conclusion The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non‐high‐risk areas, thus reducing the incidence of UGC by improving the UGPL detection., We performed a cross‐sectional study from October 2012 with the major national public health project—Early Screening Program in Urban China (CanSPUC) in Hunan province. In this study, we analyze the results of upper gastrointestinal cancer (UGC) screening conducted in the first 7 year of CanSPUC. And for the firstly time, we aim to develop and externally validate a nomogram for predicting the risk of UGPL, so as to provide a simple and accurate tool for risk questionnaire evaluation of UGC screening in non‐high‐incidence area.

Background and objectives To identify the optimal range and the minimum number of lymph nodes (LNs) to be examined to maximize survival time of patients with curatively resected gallbladder adenocarcinoma (GBAC). Methods Data were collected from the surveillance, epidemiology, and end results database on patients with GBAC who underwent curative resection between 2004 and 2015. A Bayesian network (BN) model was constructed to identify the optimal range of harvested LNs. Model accuracy was evaluated using the confusion matrix and receiver operating characteristic (ROC) curve. Results A total of 1268 patients were enrolled in this study. Accuracy of the BN model was 72.82%, and the area under the curve of the ROC for the testing dataset was 78.49%. We found that at least seven LNs should be harvested to maximize survival time, and that the optimal count of harvested LNs was in the range of 7 to 10 overall, with an optimal range of 10 to 11 for N+ patients, 7 to 10 for stage T1-T2 patients, and 7 to 11 for stage T3-T4 patients. Conclusions According to a BN model, at least seven LNs should be retrieved for GBAC with curative resection, with an overall optimal range of 7 to 10 harvested LNs.

BACKGROUND: Guidelines recommend mediastinal sampling first for patients with mediastinal lymphadenopathy with suspected lung cancer. The objective of this study was to describe practice patterns and outcomes of diagnostic strategies in patients with lung cancer. METHODS: This study included a retrospective cohort of 15,914 patients with lung cancer with T1-3N1-3M0 disease diagnosed from 2004 to 2013 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results or Texas Cancer Registry Medicare-linked databases. Patients who had mediastinal sampling as their first invasive test were classified as guideline consistent; all others were guideline inconsistent. Propensity matching was used to compare the number of tests performed, and multivariable logistic regression was used to compare the incidence of complications. RESULTS: Guideline-consistent care increased from 23% to 34% of patients from 2004 to 2013 (P < .001). Use of endobronchial ultrasound-guided transbronchial needle aspiration increased from 0.1% to 25% of all patients (P < .001), and mediastinal sampling increased from 54% to 64% (P < .0001). Guideline-consistent care was associated with fewer thoracotomies (38% vs 71%; P < .001) and CT scan-guided biopsies (10% vs 75%; P < .001) than guideline-inconsistent care but more transbronchial needle aspirations (59% vs 12%; P < .001). Guideline-consistent care was associated with fewer pneumothoraxes (5.1% vs 22%; P < .001), chest tubes (0.9% vs 4.4%; P < .001), hemorrhages (3.5% vs 5.8%; P < .001), and respiratory failure events (2.7% vs 3.7%; P = .047) than guideline-inconsistent care. Bronchoscopic mediastinal sampling was associated with fewer complications than surgical mediastinal sampling. CONCLUSIONS: Guideline-consistent care with mediastinal sampling first was associated with fewer tests and complications. Quality gaps decreased with the introduction of endobronchial ultrasound-guided transbronchial needle aspiration but persist. Gaps include failure to sample the mediastinum first, failure to sample the mediastinum at all, and overuse of thoracotomy.

This study compared Sheng Xue Ning (SXN) tablets with ferrous succinate (FS) tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis (MHD). A total of 94 patients undergoing MHD were randomly assigned to an experiment group (receiving oral SXN tablets, SXN group) and a control group (orally given FS tablets, FS group) and followed up for 12 weeks. Erythropoietin (EPO) was used in both groups. The efficacy was assessed by detecting the subsequent changes in hemoglobin (Hb), serum iron (SI), SF and transferrin saturation (TSAT). At the 12th week, Hb and TSAT levels in both groups were significantly increased compared to those in the screening period (P

A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat–egg–milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.

Summary Recent attempts have been made to direct the sensory neurotisation of free superficial circumflex iliac artery (SCIA) flaps. However, donor nerves enabling sensory recovery are limited. We report our findings in fifteen patients who underwent distal limb defect reconstruction using a sensate SCIA flap, including the lateral cutaneous branch of the subcostal nerve (LCSN), between August 2017 and September 2018. The distance from the anterosuperior iliac spine to the point where the LCSN crossed the iliac crest ranged between 6.5 and 10 cm. The diameter ranged between 1.5 and 4.0 mm. The flap size ranged between 8 × 4 and 13 × 10 cm2. All of the flaps survived uneventfully. Tests of sensory modalities, including the Semmes-Weinstein (SW) touch, vibration, pinprick, temperature and static two-point discrimination (s2PD) tests were applied in nine regions of each flap post-operatively. One or more modalities were present in at least one region at 6 months post-operatively, and the recovery of vibration perception was more consistent than that of SW touch and pinprick perception. The recovery of s2PD was noted in 4 cases over a follow-up period of more than 12 months. A reliable sensate flap with the LCSN can be considered as an attractive option for the sensory reconstruction of distal limb defects of moderate size.

Background The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC.

Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level.We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments.reRCC had reduced CD8We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8

Anti-androgenic endocrine-disrupting chemicals (EDCs) can cross the placenta to modify early offspring sexual dimorphic markers. These changes are linked to anogenital distance (AGD), which is an androgen-sensitive anthropometric parameter used as a biomarker of perineal growth and caudal migration of the genital tubercle. This review aimed to summarize strength of evidence for associations of in utero exposure to EDCs with AGD and to identify gaps and limitations in the literature so as to inform future research. We performed an electronic search of English literature in September 2019 in medical literature analysis and retrieval system online (MEDLINE), Web of Science and Toxline. We included epidemiological studies that examined in utero exposure to persistent and nonpersistent EDCs and considered AGD in offspring as an outcome. Our review contained 16 investigations examining exposure to persistent EDCs (nine studies) and nonpersistent EDCs (seven studies). Some individual studies reported an inverse association between exposure to bisphenol A (BPA), dioxins, perfluoroalkyl substances, and organochlorides and AGD in both male and female offspring. Meta-analysis of three studies found a small reduction of AGD in female offspring exposed to BPA. The number of studies per chemical is small, and number of subjects examined is limited; so, replication of these results is needed. To achieve more specificity and better replication of results, future studies should establish the association of nonpersistent EDCs using multiple urine samples, evaluate the cumulative impact of exposure to a mixture of anti-androgenic chemicals, and offer adequate consideration of more maternal- and children-related confounding factors.

Background and Purpose The aim of this study is to identify the early predictors for delayed cerebral ischemia (DCI) and develop a risk stratification score by focusing on the early change after aneurysmal subarachnoid hemorrhage (aSAH). Methods The study retrospectively reviewed aSAH patients between 2014 and 2015. Risk factors within 72 hours after aSAH were included into univariable and multivariable logistic regression analysis to screen the independent predictors for DCI and to design a risk stratification score. Results We analyzed 702 aSAH patients; four predictors were retained from the final multivariable analysis: World Federation of Neurosurgical Societies scale (WFNS; OR = 4.057, P

When patients attend with medical complaints such as abnormal leucorrhea, the clinician should consider the possibility of an infection in the lower genital tract, such as vulvovaginal candidiasis (VVC). At that point, it is appropriate to then further assess the typical clinical manifestation, diagnosis, and routine management of the infection. However, sometimes, it is not possible to detect any pathogen at all through standard diagnostic techniques. In such a scenario, what happens to these patients? It has been suggested that the human microbiome may be thought of as the “second human genome,” and recent data published in the field have revealed that the urogenital site contributes approximately 9% of the entire human microbiome. This compares with the gastrointestinal tract, which comprises 29%.[1] The vaginal microbiome is an intricate and dynamic system of bacteria flora where various microbial communities exhibit considerable diversity and density. Any imbalance in the naturally occurring bacterial flora may result in infections such as VVC, bacterial vaginitis (BV), or aerobic vaginitis (AV).[2,3] In order to navigate and explore this exciting microecosystem and its inhabitants, we need a valid roadmap. Changes to several microecological indicators of the vaginal microbiome providing a unique “signature” for lower genital tract infections are usually identified by clinical microbiology laboratories through vaginal swab cultures and microscopic examinations. A multicenter epidemiological study used the Vaginal Microecology Evaluation System (VMES) as a tool to analyze the vaginal microbiomes in most areas of China.[4] The aim of this article is to introduce knowledge on changes to the vaginal microecological environment and inform users of the VMES in diagnosing and managing the broad range of vaginal infections that can occur.

Background: Chemotherapy resistance is a major problem in breast cancer treatment and a leading cause of mortality in breast cancer patients. Biomarkers for chemotherapy resistance is under investigation. Methods: Paclitaxel resistant cells were established and subjected to RNA sequencing. Analysis combined with two additional RNA-seq datasets was conducted. CapG expression in patients with adjuvant chemotherapy was studied in breast cancer resection specimens using IHC and related to pathological response and disease-free survival. Paclitaxel resistance was assessed by half-maximal inhibitory concentrations (IC50) and a mouse xenograft model. Results: Increased expression of actin-binding protein CapG strongly correlated with the resistance to paclitaxel chemotherapy and decreased probability to achieve pathological complete response in breast cancer patients. Overexpressing CapG significantly enhanced paclitaxel resistance in breast cancer cells and xenograft tumors. High CapG level also significantly correlated with shorter relapse-free survival as well as hyper-activation of PI3K/Akt signaling in breast cancer patients. Mechanistically, CapG enhanced PIK3R1 expression which led to increased PI3K/Akt activation. Unexpectedly, CapG was found to bind to the variant-specific promoter of PIK3R1/P50 and directly enhance its transcription. We also identified p300/CBP as a transcriptional coregulator of CapG, which is recruited to PIK3R1 promoter through interaction with CapG, thereby increasing PIK3R1/P50 transcription by enhancing histone H3K27 acetylation. Consistently, inhibiting p300/CBP substantially decreased CapG-dependent upregulation of PIK3R1/P50 and subsequent PI3K/Akt activation, resulting in increased sensitivity to paclitaxel treatment in breast cancer cells. Conclusion: High CapG levels may predict poor paclitaxel response in breast cancer patients. Targeting CapG-mediated hyperactivation of PI3K/Akt pathway may mitigate resistance to chemotherapy in breast cancer.

Background: Lamin B2 (LMNB2) is involved in chromatin remodelling and the rupture and reorganization of the nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, there are few reports on the expression and function of LMNB2 in colorectal cancer.Methods: A tissue microarray (TAM) was used to detect the expression of LMNB2 in 226 colorectal cancer tissues and the corresponding adjacent tissues. The CCK-8 colorimetric assay, EdU incorporation analyses, colony formation assays and cell cycle experiments were used to evaluate the effect of LMNB2 on colorectal cancer cell proliferation in vitro, and a mouse tumorigenic model was used to study the effect of LMNB2 on colorectal cancer cells in vivo. The main pathways and genes regulated by LMNB2 were detected by RNA sequencing. Dual-luciferase reporter assays were conducted to test the direct binding between LMNB2 and p21, and ChIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter.Results: The results showed that LMNB2 expression is increased in colorectal cancer tissues. Highly expressed LMNB2 is associated with tumour size and TNM stage. Multivariate Cox analysis showed that LMNB2 can be used as an independent prognostic factor in patients with colorectal cancer. Functional assays indicated that LMNB2 obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. LMNB2 facilitates cell proliferation via regulating the p21 promoter, whereas LMNB2 had no effect on cell apoptosis in terms of mechanism.Conclusion: LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, indicating the potential value of LMNB2 as a clinical prognostic marker and molecular therapeutic target.

Background Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. Methods Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann–Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. Results The mean incubation was 8.67 (95% confidence interval, 6.78–10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86–12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (

Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy.The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020.1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection.Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

Graves’ disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

Background This study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI). Methods Radiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)–Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan–Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation. Results Radiomic signature (p p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score Conclusions Radiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.

BACKGROUND Given the reliability of circRNAs in symbolizing cancer progression, this investigation was designed to expound the involvement of hsa_circ_0028007 in regulating chemosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS Altogether, 241 pairs of NPC tissues and para-cancerous normal tissues were collected to identify NPC-symbolic circRNAs, which have been screened by circRNA microarray in advance. Expressions of the circRNAs were determined by means of real-time polymerase chain reaction (PCR). Besides, human NPC cell lines (ie, CNE2 and HONE1) were transfected by si-hsa_circ_0028007 and si-NC. Scratch assay, transwell assay, and MTT assay were performed to assess migration, invasion, and paclitaxel/cisplatin-resistance of NPC cell lines. RESULTS Hsa_circ_0028007 expression was abnormally heightened within NPC tissues in comparison with matched non-tumor tissues (P

Objective: The aim of this study is to describe the clinical characteristics and intraoperative findings and further evaluate the efficacy of endoscopic ossiculoplasty for the management of isolated congenital ossicular chain malformation. Methods: A retrospective study was performed on 16 ears (15 patients) with the isolated congenital ossicular chain malformation who underwent endoscopic ossiculoplasty in our department from May 2017 to January 2019. Endoscopic exploratory tympanotomy was conducted to check the ossicular chain; at the same time, endoscopic ossiculoplasty was performed depending on intraoperative findings. Air-conduction thresholds, bone-conduction thresholds, and air-bone gaps (ABGs) were measured before and after surgery, and the hearing outcome was assessed at 6 months postoperatively. Results: The most common malformations of ossicular chain were the missing of the incus long process and stapes suprastructure. A serial assessment of the hearing status was conducted before and 6 months after surgery. It showed the mean postoperative pure-tone average (PTA) was significantly reduced, and the mean postoperative ABG was obviously closed, respectively ( P < .001). The mean PTA gain was 36.3 ± 8.6 dB, and the ABG closure was 35.1 ± 8.3 dB; ABG closure to 20 dB or less and ABG closure to 10 dB or less were achieved in 14 cases (87.5%) and 5 cases (31.3%), respectively. No differences were observed in postoperative hearing outcome between type Ⅲ cases and type Ⅳ cases; however, cases with partial ossicular replacement prosthesis implantation showed a larger hearing gain ( P = .049) and a higher proportion of postoperative ABG less than 10 dB ( P = .021). No facial palsy and significant sensorineural hearing loss occurred; all patients completed the surgery without the need of canalplasty, and the chorda tympani nerve was preserved in all patients. Conclusions: This research showed endoscopic surgery was effective in the diagnosis and management of isolated congenital ossicular chain malformation; the endoscopic ossiculoplasty provides an alternative method to manage congenital ossicular chain malformation, with comfortable hearing outcome and the advantage of excellent vision and less invasion.

Supplemental Digital Content is available in the text, Studies of maternal oral contraceptive pill (OCP) exposure and the offspring's risk of atopic diseases are of current interest due to concerns about widespread use of OCP before or during pregnancy. We evaluated whether maternal OCP exposure is associated with an increased risk of atopic diseases by reviewing the literature and performing a meta-analysis. The PubMed and Embase databases were searched to identify potential studies for inclusion. Three common atopic outcomes were included: asthma, eczema, and rhinitis. We found 693 titles, abstracts, and citations, and 6 studies were included in this analysis. A meta-analysis revealed that maternal OCP exposure was associated with higher odds of asthma (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.02–1.19; P = .014), rhinitis (OR 1.34; 95% CI 1.07–1.68; P = .011) during childhood, whereas there was no association with eczema (OR 1.17; 95% CI 0.81–1.68; P = .383). This analysis was limited by the small number of studies included and the limited adjustments for the possible confounders in the studies. Current evidence suggests that maternal OCP exposure increases the risk for respiratory allergic diseases (asthma and rhinitis) in the offspring, but not for eczema. Given the few studies included, future larger, prospective studies that control for important confounders are needed to verify our findings.

Background: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, “light-bulb” procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (β-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH.Methods: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes.Results: The 5-years survival rate of using β-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P < 0.05). 2 hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative.Conclusions: Our results suggest that “light-bulb” procedure grafting with β-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

Objective: The purpose of this study is to investigate the relationship between N-methylN'-nitro-N-nitrosoguanidine (MNNG)-induced lung adenocarcinoma mouse of different stages and the level of exosomes in serum. Methods: Fifty KM mice (4 weeks old, weighing 18-22 g, female) were selected for experiment. MNNG was applied to induce lung adenocarcinoma in mice for model establishment. HE staining method was used to observe pathological changes of lung tissues. Exosomes in serum were extracted, and observed under a Transmission Electron Microscopy (TEM). Western blot was employed to examine the protein levels of exosome markers TSG101 and CD63. Results: HE staining results suggested MNNG-induced lung adenocarcinoma model mice were successfully constructed. The morphology of exosomes in serum of mouse model was observed under an Electron Microscopy, showing clear membrane structures presenting as saucer or concave hemisphere. In addition, the protein level of exosome marker CD63 in advanced mouse model was significantly up-regulated relative to that in the control group. Meanwhile, the expression of exosome marker protein TSG101 was found to be markedly increased in mouse models by comparison with that in control cases. Conclusion: In lung adenocarcinoma model mice, the occurrence and development of lung adenocarcinoma are greatly correlated with the expression level of exosomes in serum, which provides theoretical basis for the diagnosis of pathological staging of lung adenocarcinoma by exosomes.

Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. ααIntraperitoneal administration was an efficient route for targetingCollectively, these results demonstrate the all-in-one potential of

Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P .05). The PaoThere were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

Background: Whether occupation has an impact on contact heat evoked potential (CHEP) results has not been investigated. In this study, we investigated the difference of CHEP parameters between knowledge workers and unskilled labors. Methods: A total of 137 healthy participants were recruited between November 20, 2014 and December 31, 2016. All participants underwent neurologic examination, laboratory examination, and nerve conduction studies. CHEP was performed on four body sites: the upper border of the distal third of the volar forearm, the upper border of the distal third of the lateral leg, the spinous process of seventh cervical vertebrae (C7), and the spinous process of 12th thoracic vertebrae (T12). Independent t test and nonparametric test were performed using SPSS software to compare the difference of the CHEP parameters between knowledge workers and unskilled labors. Results: The "N2 latency/height" (Z = -2.290, P = 0.022) and "P2 latency/height" (Z = -2.020, P = 0.043) on the volar forearm of unskilled labors significantly increased than those of knowledge workers. The "N2 latency/height" (F = 6.348, P = 0.016) and "P2 latency/height" (F = 5.920, P = 0.018) in the distal leg of unskilled labors significantly prolonged than those of knowledge workers. The N2-P2 amplitude (F = 5.797, P = 0.020) in the distal leg of unskilled labors significantly decreased than those of knowledge workers. Conclusions: Our study found that significantly prolonged N2 latency and P2 latency and significantly decreased N2-P2 amplitude in the distal leg and the volar forearm in unskilled labors as to knowledge workers. Key words: Contact heat evoked potential; Occupation; Nerve conduction studies

Three novel single crystals of the metal-based complexes Cu-1, Cu-2, and Co-1 were obtained and characterized. Compared with Cu-2 and Co-1, Cu-1 showed remarkable activities of anti-cervical cancer, anti-cisplatin-resistant non-small cell lung cancer and anti-angiogenesis by downregulating the expressions of important proteins in the VEGF/VEGFR2 signaling pathway to inhibit angiogenesis and cancer cell proliferation, induce apoptosis, and suppress migration and metastasis. Moreover, Cu-1 dramatically inhibited the expression of the anti-apoptotic protein Bcl-2 and up-regulated the expressions of the proapoptotic proteins caspase-9 and Bax to induce the apoptosis of tumor cells, simultaneously decreasing the density of endothelial cells to inhibit tumor angiogenesis in cisplatin-resistant tumors.

Objective The purpose of this study was to investigate structural and functional alterations of the brain in the patients with stable chronic obstructive pulmonary disorder (COPD) and further investigate how these alterations correlated to parameters of pulmonary function test, cognitive function and disease duration in patients with COPD. Method Forty-five patients with stable COPD and forty age- and gender-matched healthy controls were enrolled into this study. Both resting-state fMRI and structural MRI were acquired for each participant. Voxel-based morphology was utilized to analyze alterations of the grey matter volume (GMV), and the seed-based resting-state functional connectivity (FC) was used to evaluate the network-level functional alterations. Results Compared to healthy controls, patients with stable COPD showed decreased GMV in the left supramarginal gyrus/precentral gyrus (SMG/PreCG), bilateral posterior midcingulate cortex (pMCC), right middle occipital gyrus (MOG) and right SMG. Furthermore, COPD patients mainly showed decreased FC within the visual network, frontoparietal network and other brain regions. Subsequent correlational analyses revealed that the decreased FC within visual network, frontoparietal network were positively correlated with the Montreal Cognitive Assessment score, language-domain score, attention-domain score and disease duration in patients with COPD. Conclusion Our findings provided evidence that COPD patients showed decreased GMV and regional and network-level functional alterations within the visual network, frontoparietal network and other networks. We speculated that atrophic GMV and FC of visual network and frontoparietal network are involved in the neural mechanism of mild cognitive impairment in stable COPD patients.

Background Studies have demonstrated that liver enzymes are associated with metabolic syndrome (MetS). However, little information is available regarding these relationships in elderly populations. Our present study aimed to explore the associations between liver enzymes and the risk of MetS in elderly populations. Methods This cross-sectional study included 1444 elder participants (970 men and 474 women) who attended annual physical examinations. Univariate and multivariate logistic regressions were performed to estimate the associations between liver enzymes and the risk of MetS and its components according to quartiles of the concentration of each liver enzyme. Results The prevalence of MetS and its components increased remarkably with increasing quartiles of alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) but not with aspartate aminotransferase (AST) in the elderly. Compared with subjects in the bottom quartile, the adjusted odds ratio for MetS in the highest ALT, GGT and ALP quartiles were 1.78 (95% CI 1.21–2.61), 2.58 (95% CI 1.77–3.78) and 1.85 (95%CI 1.27–2.70) respectively. No statistically significant increases in the odds ratio for MetS according to increased quartiles of AST were found in either the univariate or multivariate logistic regression analyses. Conclusions Elevated liver enzymes levels (mainly ALT, GGT and ALP but not AST) are positively associated with the prevalence of MetS in elderly populations.

Background This study aimed to evaluate the safety and tolerability for variable dosages of a novel hepatitis E vaccine p179. Methods The randomized open-label parallel control phase 1 clinical trial enrolled 120 eligible participants aged 16–65 years in Jiangsu Province, China. The experimental groups were randomized to receive different dosages of 20 μg, 30 μg, and 40 μg Hepatitis E Virus (HEV) p179 vaccines, with the 30 μg HEV vaccine p239 Hecolin as control, and vaccinated at 0, 1 and 6 month intervals. Participants were observed for solicited local and systemic adverse reactions (ARs) occurring within 7 days after each vaccination, and any serious adverse events (SAEs) occurring within 6 months post-vaccination. Blood samples were collected from participants 3 days before and after each injection, to determine the blood routine and serum biochemical indexes. Results The solicited local ARs incidence in experimental groups were significantly lower than that of the control group (P = 0.027). The difference between solicited total and systemic ARs incidence of experimental groups and the control group were not significant (P > 0.05). Similar patterns were observed when the analyses were performed on the group having ARs of varying grades and symptoms. All changes in blood biochemical indexes and routine blood tests before and after different vaccinations were mild (grade 1) or moderate (grade 2), and the difference in experimental groups and the control group were not statistically significant. No vaccine related SAEs occurred in any of the subjects during the study. Conclusion Three different dosages of HEV p179 vaccine were deemed safe and well tolerated. No vaccine-associated SAEs were identified, and the 30 μg dosage formulation was selected for further investigation for efficacy. Clinical trials registration number: 2012L01657 .

Background: In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN. Methods: Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test. Results: Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) ( r = 0.372, P = 0.025), and proximal ( r = 0.383, P = 0.021) and distal ( r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve ( r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups ( χ 2 = 9.901, P = 0.007). IENFD was significantly decreased ( χ 2 = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups ( χ 2 = 8.172, P F = 4.336, P = 0.021) and distal ( F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups. Conclusions: IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.

BACKGROUND The transcription factor 21 (TCF21) gene is believed to be a tumor suppressor gene. TCF21 gene polymorphisms were found to play a role in the tumorigenesis of some solid malignancies. We raised a hypothesis that genetic polymorphisms of TCF21 were correlated with risk and prognosis of osteosarcoma. MATERIAL AND METHODS We recruited 225 young osteosarcoma individuals and 250 cancer-free controls. Five tagging SNPs (TCF21 rs2327429 T>C, rs2327433 A>G, rs2327433 A>G, rs12190287 C>G, and rs4896011 T>A) were genotyped. Preserved DNA samples from blood underwent PCR analysis for genotyping. RESULTS rs12190287 C>G is a good predictor of osteosarcoma risk and outcomes. The CG and GG genotypes of rs12190287 predict elevated risk of osteosarcoma. Besides, rs12190287 CG and GG genotypes are associated with Enneking stage and potential in forming metastasis of osteosarcoma. CONCLUSIONS Genetic polymorphisms of TCF21 are potentially predictive for osteosarcoma risk and outcomes.

Background: Several previous studies have shown that snoring is associated with glucose metabolism and the development of diabetes, but rare study has shown the association between snoring frequency and prediabetes, particularly in China. We hypothesized that individuals who snore might have a higher risk of prediabetes. This study aimed to investigate the association between self-reported snoring and prediabetes in a Chinese population. Methods: A cross-sectional study was performed in three large communities of Beijing from December 2011 to August 2012 by recruiting individuals aged ≥40 years old. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. A 75 g oral glucose tolerance test was performed in individuals without diabetes. Blood samples of all participants were collected; blood glucose and blood fat levels were measured. Multivariate logistic regression models were built to assess the association between snoring frequency and prediabetes. Results: A total of 13,592 participants (female: 66.56%; mean age: 56.8 ± 7.9 years; mean body mass index: 25.5 ± 3.4 kg/m2) were included in the final analysis. Of these, 30.9% were diagnosed with prediabetes, while 41.3% and 25.4% had occasional and habitual snoring, respectively. Habitual snoring was associated with an increased risk of prediabetes (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1–1.4, P < 0.001), after adjusting for diabetes and sleep-related confounders in the multivariable models. Habitual snoring was also associated with isolated impaired fasting glucose (IFG; OR: 1.3, 95% CI: 1.0–1.6; P < 0.001) and isolated impaired glucose tolerance (IGT; OR: 1.3, 95% CI: 1.2–1.5; P < 0.001), but not IFG + IGT (OR: 1.1, 95% CI: 0.9–1.4; P = 0.281). When stratified by total cholesterol (TC) levels, this association between habitual snoring and prediabetes was observed only in individuals with TC

Angiogenesis is a critical compensation route, which has been demonstrated in the brain following ischemic stroke; however, few studies have investigated angiogenesis in chronic intracranial atherosclerosis disease (ICAD). We used 68Ga-NOTA-PRGD2 positron emission tomography/computed tomography based imaging to detect angiogenesis in chronic ICAD and to explore the factors that may have affected it. A total of 21 participants with unilateral severe chronic ICAD were included in the study. Of the 21 participants, 19 were men; the mean (SD) age was 52 (15) years. In 18 participants, we observed elevated 68Ga-NOTA-PRGD2 uptake in the peri-infarct, subcortical, and periventricular regions of the lesioned side, with a higher 68Ga-NOTA-PRGD2 SUVmax compared to that in the contralateral hemisphere (0.15 vs. 0.06, p=0.001). The 18F-FDG PET SUVmax was significantly lower on the lesioned side (11.28 vs. 13.92, p=0.001). Subgroup analyses revealed that the recent group (max than the remote group (>6 months) (6.73 vs. 2.36, p

Purpose Head and neck tumors that involve the craniomaxillofacial region are classified as stage IVb disease and are clinically challenging. In this study, the outcomes of craniofacial resection and craniofacial reconstruction in patients with recurrent malignant tumors involving the craniomaxillofacial region were evaluated. Patients and Methods This retrospective observational study was conducted from January 2008 to August 2015. Data collected for each patient included age, gender, tumor site, initial treatment, craniofacial resection, reconstruction flaps and complications after craniofacial resection, adjuvant treatment, and reported outcomes of craniofacial resection and craniofacial reconstruction. The χ2 test in SPSS was used to analyze the data. Results Twenty-four patients with recurrent malignant tumors involving the craniomaxillofacial region were identified who had undergone craniofacial resection at the Center of Craniomaxillofacial Surgery of Sun Yat-sen University (Guangzhou, Guangdong, China). The study population was comprised of 24 patients (15 men and 9 women; age range, 21 to 73 yr) with recurrent tumors (58.3% with squamous cell carcinoma [SCC], 41.7% with sarcoma [SA]) involving the craniomaxillofacial region who underwent craniofacial resection. Craniofacial resection consisted of orbital exenteration and maxillotomy; anterior skull base surgery, facial resection, and mandibulotomy; or ipsilateral radical neck dissection. The resultant craniomaxillofacial defects were reconstructed using extended vertical lower trapezius island myocutaneous flaps (TIMFs), temporalis myofascial flaps, or submental flaps. All patients with recurrent malignant tumor involving the craniomaxillofacial region underwent gross total resection of the tumor; 22 patients underwent craniofacial reconstruction. There were no major surgical complications. Minor flap failure and wound dehiscence in the donor site occurred in 4 patients. The follow-up period ranged from 8 to 36 months. Seven patients in the SCC group and 7 in the SA group were alive with no evidence of disease (AND), 3 in the SCC group and 2 in the SA group were alive with disease (AWD), and 4 in the SCC and 1 in the SA group died of the disease (DOD) after local recurrence or distant metastases at 8 to 18 months. There were no statistical differences among the AND, AWD, and DOD groups. Conclusions Craniofacial resection remains an effective salvage treatment for patients with recurrent SCC and SA involving the craniomaxillofacial region. The extended vertical lower TIMF is a large, simple, and reliable flap for reconstructing major defects after a craniofacial resection.

Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT.Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment.For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (P0.001), but no group difference was observed. No differences in amplitude of low-frequency fluctuation (ALFF) values were found between CCT and pCCT either pre- or post-treatment. Compared to controls, ALFF in OCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected P0.05). The ALFF in those regions was not significantly correlated to the severity of OCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared.The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks.Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved.