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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.

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value &lt, 0.05, FDR &lt, 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM.

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 China has the largest elderly population in the world; little attention has been paid to the mental health of elderly in areas of extreme poverty. This is the first study to investigate the mental health of the rural elderly in poverty state counties in Chongqing and was part of the Chongqing 2018 health literacy promotion project. Methods In 2019, a cross-sectional study was conducted to investigate the mental health status of the rural elderly in fourteen poverty state counties of Chongqing, in which a total of 1400 elderly aged ≥ 65 years were interviewed, where mental health status was measured by the ten-item Kessler10 (K10) scale. Ordered multivariate logistic regression was performed to evaluate the influencing factors related to mental health of the elderly in these areas. Results The average score of K10 in 14 poverty state counties was 17.40 ± 6.31, 47.6% was labeled as good, 30.2% was moderate, 17.0% was poor, and lastly 5.1% was bad, and the mental health status of the elderly in the northeastern wing of Chongqing was better than the one in the southeastern wing of Chongqing. A worse self-rated health was the risk factor for mental health both in the northeastern and southeastern wings of Chongqing (all P < 0.001). Lower education level (OR (95% CI) = 1.45 (1.12–1.87), P = 0.004) was a risk factor in the northeastern wing, whereas older age (OR (95% CI) = 1.33 (1.13–1.56), P = 0.001) was a risk factors in the southeastern wing. Conclusions The results showed that mental health of the elderly in poverty state counties was poor, especially in the southeastern wing of Chongqing. Particular attention needs to be paid to the males who were less educated, older, and single; female with lower annual per capital income; and especially the elderly with poor self-rated health.

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.

Dysregulated Wnt/β-catenin activation plays a critical role in cancer progression, metastasis, and drug resistance. Genotoxic agents such as radiation and chemotherapeutics have been shown to activate the Wnt/β-catenin signaling although the underlying mechanism remains incompletely understood. Here, we show that genotoxic agent-activated Wnt/β-catenin signaling is independent of the FZD/LRP heterodimeric receptors and Wnt ligands. OTULIN, a linear linkage-specific deubiquitinase, is essential for the DNA damage-induced β-catenin activation. OTULIN inhibits linear ubiquitination of β-catenin, which attenuates its Lys48-linked ubiquitination and proteasomal degradation upon DNA damage. The association with β-catenin is enhanced by OTULIN Tyr56 phosphorylation, which depends on genotoxic stress-activated ABL1/c-Abl. Inhibiting OTULIN or Wnt/β-catenin sensitizes triple-negative breast cancer xenograft tumors to chemotherapeutics and reduces metastasis. Increased OTULIN levels are associated with aggressive molecular subtypes and poor survival in breast cancer patients. Thus, OTULIN-mediated Wnt/β-catenin activation upon genotoxic treatments promotes drug resistance and metastasis in breast cancers., Genotoxic agents have been shown to activate the Wnt/β-catenin signaling but the underlying mechanism remains unclear. Here, the authors show that upon DNA damage, the deubiquitinase OTULIN activates Wnt/β-catenin signaling by inhibiting linear ubiquitination, K48-linked polyubiquitination, and proteasomal degradation of β-catenin.

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.

Background:. In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. Methods:. In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. Results:. Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P 0.05). Conclusions:. Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

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

The aim of the present study was to explore the safety and effectiveness of radiofrequency ablation (RFA) of the ciliary body for the treatment of glaucoma. A glaucoma model was established in New Zealand white rabbits, which were then treated with RFA of the ciliary body, utilizing an XL‑1‑type RF meter developed by the Chinese PLA General Hospital. After treatment, general ocular investigation, including ocular pressure was carried out, the anterior chamber was imaged via ultrasound biomicroscopy, and the pathological changes were observed via hematoxylin and eosin (H&E) staining. It was determined that the glaucoma model was successfully established in the New Zealand white rabbit by inducing high intraocular pressure (IOP). After RFA treatment, ablation spots were observed but no clear anterior chamber reaction was found. The ablation group showed a steady and continuous decrease of IOP, which was significantly lower than the model group at days 3 and 7 (P

Echinococcosis is a serious zoonotic parasitic disease transmitted from canines to humans and livestock. Periodic deworming is recommended by the WHO/OIE as a highly effective measure against echinococcosis. However, manual deworming involves significant challenges, particularly in remote areas with scarce resources. The insufficient awareness delivering praziquantel (PZQ) baits for dogs leads to low compliance rate. The aim of this study was therefore to develop a novel smart collar for dogs to address these challenges. We developed a smart Internet of Things (IoT)-based deworming collar which can deliver PZQ baits for dogs automatically, regularly, quantitatively with predominant characteristics of being waterproof, anti-collision, cold-proof and long life battery. Its performance was tested in two remote locations on the Tibetan Plateau. A cross-sectional survey was conducted to evaluate the compliance of the dog owners. Further, a randomized controlled study was performed to evaluate the difference between smart-collar deworming and manual deworming. The collar’s effectiveness was further assessed on the basis of Generalized Estimation Equations (GEE). The testing and evaluation was done for 10 smart deworming collars in factory laboratory, 18 collars attached for 18 dogs in Seni district, Tibet Autonomous Region, China, and 523 collars attached for 523 dogs in Hezuo city, Gansu province, China. The anti-collision, waterproof, and coldproof proportion of the smart collars were 100.0%, 99.5%, and 100.0%, respectively. When compared to manual deworming, the dogs’ risk of infection with Echinococcus on smart-collar deworming is down to 0.182 times (95% CI: 0.049, 0.684) in Seni district and 0.355 (95%CI: 0.178, 0.706) in Hezuo city, the smart collar has a significant protective effect. The owners’ overall compliance rate to attach the smart collars for their dogs was 89%. The smart deworming collar could effectively reduce the dogs’ risk of infection with Echinococcus in dogs, significantly increase the deworming frequency and coverage and rapidly remove worm biomass in dogs. Thus, it may be a promising alternative to manual deworming, particularly in remote areas on the Tibetan Plateau., Author summary Echinococcosis remains a critical but neglected zoonotic parasitic disease transmitted between canines and livestock or wild rodents. Dogs play a key role in Echinococcus granulosus sensu lato (s.l.) and E. multilocularis transmission, dual infection also occurs in dogs in co-endemic regions in China. The initial egg-production phase occurs over a span of 34–58 days (E. granulosus) or 28–35 days (E. multilocularis) following infection. The free-living eggs, voided with faeces of the definitive host, can withstand extreme weather conditions and remain viable for 240 days (E. granulosus) or 41 months (E. multilocularis) in the environment. Removal or reduction of the worm biomass in dogs will have the greatest and fastest effect in terms of reducing active transmission. In China, although significant efforts have been expended to achieve monthly manual deworming, the actual frequency and coverage thereof remain low; therefore, Echinococcus spp. is still highly prevalent among dogs. Moreover, echinococcosis transmission is still rampant, as the heavy disease burden suggests. We propose a novel, smart, Internet of Things (IoT)-based deworming tool that can deliver PZQ baits to dogs regularly and automatically. It could increase the deworming frequency and coverage significantly, reduce the risk of infection by down to 0.182–0.355 times, and prevent canine infections by removing the worm biomass in dogs rapidly. This deworming collar could also potentially prevent the transmission of echinococcosis from dogs to humans and livestock completely. It may be an excellent alternative to existing manual deworming methods, and the difficulties associated with performing deworming in remote areas with scarce resources can be overcome. Since the discovery of PZQ as the most effective antiworm drug, few breakthroughs have been achieved in terms of novel tools and technologies for the control of echinococcosis. Over the last 50 years, echinococcosis control measures have lagged to keep up with the World Health Organization (WHO) roadmap for the elimination of the disease owing to the practical difficulties in remote areas with scarce resources as well as the lack of promotion of new technologies. We expect the proposed smart deworming collar to herald the development of more innovative technologies for controlling echinococcosis by accelerating the elimination of the disease.

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.