Determinants of depressive symptoms at individual, school and province levels: a national survey of 398,520 Chinese children and adolescents.

OBJECTIVES: The aims of this study were to describe the national distribution of depressive symptoms in Chinese children and adolescents, to examine the determinants of depressive symptoms at individual, school and province levels and to assess the gender and age differences in the effect of school factors on depressive symptoms. STUDY DESIGN: This was a national cross-sectional study. METHODS: A school-based online survey was conducted in mainland China from between December 1, 2021, and January 1, 2022. A total of 398,520 eligible participants were included in the analysis. School-level data were drawn from students, headteachers and Baidu Maps, and province-level data were obtained from the national human development report. The Patient Health Questionnaire-2 was used to measure depressive symptoms. RESULTS: Areas with the highest mean scores for depressive symptoms were in the northeastern, inner central and southwestern regions of China. At the individual level, younger age, male sex, being an only child, Han ethnicity, lower body mass index, more days of exercise, less drinking and smoking behaviours, higher subjective family socio-economic status (SES) and popularity in school were related to fewer depressive symptoms; however, objective family SES and maternal education were not related to fewer depressive symptoms. The school-level variables of public status, psychological activities and psychological courses and province-level variable of higher Human Development Index were associated with fewer depressive symptoms. The effect of psychological courses and activities on depressive symptoms was greater in females. CONCLUSIONS: The results showed multilevel factors related to depressive symptoms and emphasised the importance of implementing school-based psychological activities to ameliorate depressive symptoms in Chinese children and adolescents across age and gender.

The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a disease caused by insufficient blood supply in the brain in newborns during the perinatal period. Severe HIE leads to patient death, and patients with mild HIE are at increased risk of cognitive deficits and behavioral abnormalities. The NMDA receptor is an important excitatory receptor in the central nervous system, and in adult hypoxic-ischemic injury both subtypes of the NMDA receptor play important but distinct roles. The GluN2A-containing NMDA receptor (GluN2A-NMDAR) could activate neuronal protective signaling pathway, while the GluN2B-NMDAR subtype is coupled to the apoptosis-inducing signaling pathway and leads to neuronal death. However, the expression level of GluN2B is higher in newborns than in adults, while the expression of GluN2A is lower. Therefore, it is not clear whether the roles of different NMDA receptor subtypes in HIE are consistent with those in adults. We investigated this issue in this study and found that in HIE, GluN2B plays a protective role by mediating the protective pathway through binding with PSD95, which is quite different to that in adults. The results of this study provided new theoretical support for the clinical treatment of neonatal hypoxic ischemia.

Development of a novel combined nomogram integrating deep-learning-assisted CT texture and clinical-radiological features to predict the invasiveness of clinical stage IA part-solid lung adenocarcinoma: a multicentre study.

AIM: To develop a novel combined nomogram based on deep-learning-assisted computed tomography (CT) texture (DL-TA) and clinical-radiological features for the preoperative prediction of invasiveness in patients with clinical stage IA lung adenocarcinoma manifesting as part-solid nodules (PSNs). MATERIALS AND METHODS: This study was conducted from January 2015 to October 2021 at three centres: 355 patients with 355 PSN lung adenocarcinomas who underwent surgical resection were included and classified into the training (n=222) and validation (n=133) cohorts. PSN segmentation on CT images was performed automatically with a commercial deep-learning algorithm, and CT texture features were extracted. The least absolute shrinkage and selection operator was used for feature selection and transformed into a DL-TA score. The combined nomogram that incorporated the DL-TA score and identified clinical-radiological features was developed for the prediction of pathological invasiveness of the PSNs and validated in terms of discrimination and calibration. RESULTS: The present study generated a combined nomogram for predicting the invasiveness of PSNs that included age, consolidation-to-tumour ratio, smoking status, and DL-TA score, with a C-index of 0.851 (95% confidence interval: 0.826-0.877) for the training cohort and 0.854 (95% confidence interval: 0.817-0.891) for the validation cohort, indicating good discrimination. Furthermore, the model had a Brier score of 0.153 for the training cohort and 0.135 for the validation cohort, indicating good calibration. CONCLUSION: The developed combined nomogram consisting of the DL-TA score and clinical-radiological features and has the potential to predict the individual risk for the invasiveness of stage IA PSN lung adenocarcinomas.

[Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City].

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

An exploration of the relationship between wastewater viral signals and COVID-19 hospitalizations in Ottawa, Canada.

Monitoring of viral signal in wastewater is considered a useful tool for monitoring the burden of COVID-19, especially during times of limited availability in testing. Studies have shown that COVID-19 hospitalizations are highly correlated with wastewater viral signals and the increases in wastewater viral signals can provide an early warning for increasing hospital admissions. The association is likely nonlinear and time-varying. This project employs a distributed lag nonlinear model (DLNM) (Gasparrini et al., 2010) to study the nonlinear exposure-response delayed association of the COVID-19 hospitalizations and SARS-CoV-2 wastewater viral signals using relevant data from Ottawa, Canada. We consider up to a 15-day time lag from the average of SARS-CoV N1 and N2 gene concentrations to COVID-19 hospitalizations. The expected reduction in hospitalization is adjusted for vaccination efforts. A correlation analysis of the data verifies that COVID-19 hospitalizations are highly correlated with wastewater viral signals with a time-varying relationship. Our DLNM based analysis yields a reasonable estimate of COVID-19 hospitalizations and enhances our understanding of the association of COVID-19 hospitalizations with wastewater viral signals.

[The effect of Helicobacter pylori infection on duodenal bulbar microbiota in children with duodenal ulcer].

Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp-positive and Hp-negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and ß diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T-test, Rank sum test or χ2 test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp-negative group, the Hp-positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z=2.00, P=0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z=-2.24, P=0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z=-2.10, P=0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z=-2.01, P=0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp-positive group (LDA=4.89, P=0.045), while Streptococcus and Fusobacterium significantly enriched in Hp-negative group (LDA=3.28, 3.11;P=0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp-positive group were significantly higher than that in Hp-negative group (all P<0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P<0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.

The SARS-CoV-2 rS1-E-PLGA nanovaccine and evaluation of its immune effect in BALB/c mice.

OBJECTIVE: Vaccination is an important method for preventing COVID-19 infection. However, certain vaccines do not meet the current needs. To improve the vaccine effect, discard ineffective antigens, and focus on high-quality antigenic clusters, S1-E bivalent antigens were designed. MATERIALS AND METHODS: Vaccine delivery is performed using poly (lactic-co-glycolic acid) (PLGA). Here, the recombinant S1-E (rS1-E) was covered on PLGA and injected intramuscularly into mice. In total, 48 BALB/c mice were randomly divided into six groups with 8 mice in each group. The mice received intramuscular injections. Prior to vaccination, the hydrophobicity of the rS1-E and the antigenic site of the E protein were both analysed. The morphology, zeta potential, and particle size distribution of rS1-E-PLGA were examined. Anti-S1 and anti-E antibodies were detected in mouse serum by ELISA. Neutralising an-tibodies were detected by co-incubating the pseudovirus with the obtained serum. IL-2 and TNF-α levels were also measured. RESULTS: The designed recombinant S1-E protein was successfully coated on PLGA nanoparticles. rS1-E-PLGA nanovaccine has suitable size, shape, good stability, sustained release and other characteristics. Importantly, mice were stimulated with rS1-E-PLGA nanovaccines to produce high-titre antibodies and a good cellular immune response. CONCLUSIONS: Our results indicate that rS1-E-PLGA nanovaccine may provide a good protective effect, and the vaccine should be further investigated in human clinical trials for use in vaccination or as a booster.

[Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types].

OBJECTIVE: To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types. METHODS: This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations. RESULTS: In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05). CONCLUSION: CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.

[Analysis of risk factors for post-polypectomy bleeding and polyp recurrence after colonoscopic polypectomy in children].

Objective: To explore the incidence and the risk factors of post-polypectomy bleeding and polyp recurrence after colonoscopic high-frequency electrocoagulation snare polypectomy. Methods: Clinical data of 1 826 children who underwent colonoscopic high-frequency electrocoagulation snare polypectomy in the Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2020 was retrospectively analyzed. Demographic characteristics, endoscopic manifestations, pathological features, diagnosis, occurrence of post-polypectomy bleeding and polyp recurrence were collected. The associated risk factors were analyzed by Logistic regression. Results: A total of 1 826 children (1 191 males and 635 females) with 1 967 polypectomies were included. The age was 4.6 (3.2, 6.4) years at initial diagnosis. According to the initial colonoscopy, 1 611 children (88.2%) had solitary polyps, 1 707 children (93.5%) had pedicled polyps, 1 151 children (63.0%) had polyps involving the rectum, and 1 757 children (96.2%) had hamartomatous polyps. Polyposis syndromes were diagnosed in 73 children (4.0%). The post-polypectomy bleeding occurrence was 3.8% (75/1 967). Polyps recurred in 88 children (4.8%). Girls (OR=2.01, 95%CI 1.26-3.23) and sessile polyps (OR=2.28, 95%CI 1.15-4.49) were risk factors for post-polypectomy bleeding (both P<0.05). Multiple polyps (OR=17.49, 95%CI 9.82-31.18), right-colon involvement (OR=3.44, 95%CI 1.89-6.26) and non-hamartoma (OR=2.51, 95%CI 1.04-6.07) were risk factors for polyp recurrence (all P<0.05). Conclusions: Colonoscopic high-frequency electrocoagulation snare polypectomy has low incidence of post-polypectomy bleeding and polyp recurrence. Female patients and sessile polyps have higher risk for post-polypectomy bleeding. Multiple polyps, right-colon involvement and non-hamartoma polyps increase the risk for polyp recurrence.

CT texture analysis-based nomogram for the preoperative prediction of visceral pleural invasion in cT1N0M0 lung adenocarcinoma: an external validation cohort study.

AIM: To develop a nomogram based on computed tomography (CT) texture analysis for the preoperative prediction of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma. MATERIALS AND METHODS: A dataset of chest CT containing lung nodules was collected from two institutions, and all surgically resected nodules were classified pathologically based on the presence of visceral pleural invasion. Each nodule on the CT image was segmented automatically by artificial-intelligence software and its CT texture features were extracted. The dataset was divided into training and external validation cohorts according to the institution, and a nomogram for predicting visceral pleural invasion was developed and validated. RESULTS: Of a total of 313 patients enrolled from two independent institutions, 63 were diagnosed with visceral pleural invasion. Three-dimensional (3D) CT long diameter, skewness, and sphericity, and chronic obstructive pulmonary disease were identified as independent predictors for visceral pleural invasion by multivariable logistic regression. The nomogram based on multivariable logistic regression showed great discriminative ability, as indicated by a C-index of 0.890 (95% confidence interval [CI]: 0.867-0.914) and 0.864 (95% CI: 0.817-0.911) for the training and external validation cohorts, respectively. Additionally, calibration of the nomogram revealed good predictive ability, as indicated by the Brier score (0.108 and 0.100 for the training and external validation cohorts, respectively). CONCLUSIONS: A nomogram was developed that could compute the probability of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma with good calibration and discrimination. The nomogram has potential as a reliable tool for clinical evaluation and decision-making.

[Characteristics of gastric mucosa microbiota in children with chronic gastritis and duodenal ulcer].

Objective: To investigate the differences of gastric mucosa microbiota between children with chronic gastritis and duodenal ulcer under the condition of Helicobacter pylori (Hp) infection. Methods: This prospective cohort study involved 57 children with Hp infection diagnosed by gastric endoscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to "abdominal pain, abdominal distension and vomiting" between January 2018 to August 2018. According to gastroscopy and pathological examination, the children were divided into chronic gastritis group and duodenal ulcer group. Gastric mucosa from Hp infected patients were sampled, and the flora DNA was analyzed by high-throughput sequencing. The statistical difference of α diversity, ß diversity between two groups were analyzed. The relative abundance of the two groups in each taxonomic level was analyzed statistically. T test, Rank sum test or χ2 test was used for comparison between the two groups. Results: A total of 57 children diagnosed with Hp infection were enrolled in this study, including 42 cases of chronic gastritis (the age was (9.3±2.8) years, 22 males and 20 females) and 15 cases of duodenal ulcer (the age was (11.1±3.3) years, 9 males and 6 females). Alpha diversity index Chao and ACE in Hp infected chronic gastritis group were significantly higher than those in Hp infected duodenal ulcer group (217±50 vs. 183±64, t=2.088, P=0.009;218±47 vs. 192±76, t=1.566, P=0.016, respectively). The Beta-diversity index such as nonmetric multidimensional scaling (NMDS) analysis were significantly different in the two groups (analysis of similarity R=0.304, P=0.028). Among the main bacteria genera, there were 6 genera with significant differences between the two groups, which were Prevotella (0.190% (0.008%-1.983%) vs. 0.021% (0.005%-2.398%), Z=-2.537, P=0.011), Alloprevotella (0.097% (0.010%-0.813%) vs. 0.015% (0.003%-0.576%), Z=-2.492, P=0.013), Haemophilus (0.109% (0.004%-0.985%) vs. 0.014% (0.004%-0.356%), Z=-2.900, P=0.004), Neisseria (0.074% (0.004%-0.999%) vs. 0.024% (0.003%-0.255%), Z=-2.718, P=0.007), Streptococcus (0.166% (0.008%-1.869%) vs. 0.045% (0.006%-0.879%), Z=-2.537, P=0.010), and an unclassified-Microbacteriaceae (0.214% (0.060%-1.762%) vs. 0.117% (0.010%-0.954%), Z=-2.120, P=0.034). Linear discriminant analysis (LDA) effect sized analysis showed that at the genus level, only Prevotella was significantly enriched in the duodenal ulcer group (LDA=2.90, P=0.010), while Streptococcus, Neisseria and Haemophilus were significantly enriched in the chronic gastritis group (LDA=2.83, 2.82, 2.69, P=0.011, 0.007, 0.004, respectively). Conclusions: The gastric mucosal microbiota in duodenal ulcer associated with Hp is significantly different from that in chronic gastritis. Hp may promote the occurrence of peptic ulcer together with gastric microbiota.

Hmong participants' reactions to return of individual and community pharmacogenetic research results: "A positive light for our community".

Pharmacogenetic research has historically lacked racial and ethnic diversity, limiting the application of findings to minority populations. Recent studies, including the Hmong, have gauged communities' interest in participating in genomic research and receiving their individual results. This study was conducted to create a culturally and linguistically appropriate format to return pharmacogenomic results and identify Minnesota Hmong research participants' reactions to their personal and collective results. Using a community-based participatory research approach, researchers collaborated with Hmong community members to format the pharmacogenetic disclosure process. Three focus groups were completed with 24 Hmong participants and three major themes emerged using thematic analysis. Many Hmong focus group participants viewed the results positively, finding them useful for themselves and their community as a means to optimize responses to and avoid harms from medicines. However, some participants expressed concerns about harms that the pharmacogenetic information could bring, including anxiety, misunderstanding, discrimination, exploitation, and lack of a clinician involvement in interpreting and applying the result. Many participants interpreted their results through an experiential lens, trusting their experience of medicines more than trusting genetic information, and through a cultural lens, expressing the belief that environmental factors may influence how people's bodies respond to medicines by influencing their inherited flesh and blood (roj ntsha). Lastly, participants stressed the importance of disseminating the information while acknowledging the complex linguistic, educational, and cultural factors that limit understanding of the results. Researchers, genetic counselors, pharmacists, and healthcare providers should strive to return results in meaningful ways to all members of society.

The comparative safety of biological treatment in patients with axial spondylarthritis: a meta-analysis of randomized controlled trials with placebo.

OBJECTIVE: To evaluate the comparative safety of biological treatment in patients with axial spondyloarthritis (axSpA) enrolled in randomized controlled trials (RCTs) with placebo. MATERIALS AND METHODS: Studies were systematically retrieved from the Web of Science, PubMed, Cochrane Library, and Embase databases. The last search was performed on 8 June 2020. The primary outcome measures were adverse events (AEs), serious AEs, infection, serious infection, and discontinuation due to AEs. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of twenty-two trials, including 2599 participants treated with biologics and 1547 participants treated with placebo, met the inclusion criteria. There was a significantly higher risk of infection, AEs, and discontinuation due to AEs in the biologics groups compared to the placebo groups [risk ratio (RR) = 1.38, 95% confidence interval (95% CI) = 1.22-1.57, p < 0.01; RR = 1.17, 95% CI = 1.10-1.25, p < 0.01; and RR = 1.72, 95% CI = 1.03-2.87, p = 0.04, respectively], and low heterogeneity was found among the included studies (I2 = 0%, p = 0. 49; I2 = 29%, p = 0.10; and I2 = 0%, p = 0.79, respectively). The risk of serious infection and serious AEs was not significantly different between axSpA patients treated with biologics and those treated with placebo [RR = 1.62, 95% CI = 0.54-4.90, p = 0.39 and RR = 1.17, 95% CI = 0.79-1.73, p = 0.44]. Low heterogeneity was found among the included studies (I2 = 0%, p = 0.94 and I2 = 0%, p = 0.69). The subgroup analyses based on tumour necrosis factor inhibitors and interleukin antagonists did not yield significant differences. CONCLUSIONS: This meta-analysis is the first comprehensive assessment of the safety of various biological agents in axSpA patients. The use of biological agents in axSpA is generally safe and tolerable.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Cost-effectiveness of a multidisciplinary co-management program for the older hip fracture patients in Beijing.

The multidisciplinary co-management program for geriatric patients with hip fracture is cost-effective in the Chinese population and it has the potential to be scaled up in China. INTRODUCTION: The study aimed to investigate the cost-effectiveness of a multidisciplinary co-management program for patients with hip fracture in China. METHODS: Hip fracture patients who were admitted to an orthopedic hospital in Beijing were included in the multidisciplinary co-management program. The cost-effectiveness of intervention was evaluated compared to the conventional management. A Markov microsimulation model was developed to simulate lifetime costs and effectiveness. Costs including intervention, hospitalization, medications, and long-term care costs were expressed using 2019 US dollars and the healthcare perspective was adopted. Effectiveness was evaluated using both 1-year mortality-averted and quality-adjusted life years (QALYs). Costs and effectiveness were discounted at 5% per annum. The willingness-to-pay (WTP) threshold was set at $26,481 per QALY gained which was three times gross domestic product (GDP) per capita in China. One-way and probabilistic sensitivity analyses were conducted. RESULTS: The lifetime cost for the conventional management (n = 1839) and intervention group (n = 1192) was $11,975 and $13,309 respectively. The lifetime QALYs were 2.38 and 2.45 years and the first-year mortality was 17.8% and 16.1%. The incremental cost-effectiveness ratio was $19,437 per QALY gained or $78,412 per 1-year mortality-averted. Given the Chinese WTP threshold, the intervention had a 78% chance being cost-effective. The cost-effectiveness of the intervention was sensitive to cost of intervention and the proportion of patients who underwent surgery within 48 h. CONCLUSIONS: The multidisciplinary co-management program for patients with hip fracture is cost-effective and it has the potential to be scaled up in the Chinese population.

Publisher Correction: Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

The original version of this article, published on 25 November 2019, unfortunately contained a mistake.

Notch signaling is involved in regulation of LPS-induced macrophage apoptosis through JNK/NF-kB signaling pathway.

Notch signaling plays a critical role in the development and function of macrophages. The aim of the present study was to investigate the relationship between Notch signaling pathway and macrophage apoptosis after LPS stimulation. In RAW 264.7 cells, the mRNA expression of Jagged1, Hes1, Hes 5 and GM-CSF, and protein expression of NICD1 and GM-CSF were increased after LPS stimulation. Inhibition of Notch signaling by γ-secretase inhibitor DAPT and the suppression of Notch1 expression using siRNA both significantly prevented LPS induced activation of JNK and NF-kB, and simultaneously the expression of GM-CSF was also down regulated significantly. JNK inhibitor SP600125 was used to block the phosphorylation of JNK signaling, Western blot results showed that the activation of NF-kB was blocked and expression of GM-CSF was down-regulated. Finally, flow cytometry analyses showed that the Notch signaling was involved in the regulation of macrophage apoptosis after LPS stimulation. Our study showed that the Notch signaling pathway was activated and involved in the regulation of macrophage apoptosis after LPS stimulation through JNK/ NF-kB signaling regulated GM-CSF expression.

Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture. INTRODUCTION: Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years. METHODS: The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture. RESULTS: Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age. CONCLUSIONS: The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.

Network change in the ipsilesional cerebellum is correlated with motor recovery following unilateral pontine infarction.

BACKGROUND AND PURPOSE: Patients with acute pontine infarcts generally have good short-term motor outcomes; however, the mechanisms underlying this recovery of function remain unclear. METHODS: Twenty well-recovered patients with acute pontine infarcts and 20 well-recovered patients with acute striato-capsular infarcts were recruited. Fugl-Meyer assessment and resting-state functional magnetic resonance imaging were performed 1, 4 and 12 weeks after onset. Patients were further assigned to better and worse recovery subgroups according to the degree of motor recovery at the twelfth week after stroke. Voxel-wise degree centrality (DC)-behavior correlation analysis was used to identify brain regions related to changes in motor function within 12 weeks after stroke. RESULTS: A significant correlation was found between DC and Fugl-Meyer scores within 12 weeks in the ipsilesional cerebellar crus I and crus II in patients with pontine infarction and in the ipsilesional middle temporal gyrus in patients with striato-capsular infarction (all P < 0.001, AlphaSim corrected). The mean DC in these areas was higher both in the better and worse recovery subgroups at the fourth than at the first week (all P < 0.05). In addition, the mean DC values in these areas were higher in patients with better recovery at the twelfth than at the first week (P < 0.05), but such change was not found in patients with worse recovery. CONCLUSIONS: These results indicate that network changes in the ipsilesional cerebellum are correlated with motor recovery following pontine infarction. Motor recovery mechanisms may vary between pontine and striato-capsular infarcts, according to lesion location.