[Predictive value of global longitudinal strain measured by cardiac magnetic resonance imaging for left ventricular remodeling after acute ST-segment elevation myocardial infarction: a multi-centered prospective study].

OBJECTIVE: To evaluate the predictive value of global longitudinal strain (GLS) measured by cardiac magnetic resonance (CMR) feature-tracking technique for left ventricular remodeling (LVR) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week (7±2 days) and 6 months after myocardial infarction to obtain GLS, global radial strain (GRS), global circumferential strain (GCS), ejection fraction (LVEF) and infarct size (IS).The primary endpoint was LVR, defined as an increase of left ventricle end-diastolic volume by ≥20% or an increase of left ventricle end-systolic volume by ≥15% from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR. RESULTS: LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR (n=302), the patients in LVR group exhibited significantly higher GLS and GCS (P < 0.001) and lower GRS and LVEF (P < 0.001).Logistic regression analysis indicated that both GLS (OR=1.387, 95%CI: 1.223-1.573;P < 0.001) and LVEF (OR=0.951, 95%CI: 0.914-0.990;P=0.015) were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%, GLS had a sensitivity of 74.3% and a specificity of 71.9% for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR (P=0.146), but was significantly greater than those of other parameters such as GCS, GRS and IS (P < 0.05);the AUC of LVEF did not differ significantly from those of the other parameters (P>0.05). CONCLUSION: In patients receiving PCI for STEMI, GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS, GCS, IS and LVEF.

[Aqueous extract of Chuan Xiong Rhizoma enhances inhibitory effect of temozolomide against brain metastasis of melanoma in mice].

OBJECTIVE: To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma (CR) on brain metastasis of melanoma B16F10 cells in mice. METHODS: C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells, and brain tumor growth was monitored by in vivo imaging. The mouse models were then randomized for daily gavage of saline or aqueous extract of CR (equivalent crude drug concentration of 1 mg/g). Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice, and the changes in proteins associated with blood-brain barrier integrity, neuronal cell proliferation and apoptosis, and microglial cell apoptosis and activation were observed using immunofluorescence assay. The efficacy of CR combined with temozolomide (25 mg/kg) against brain metastases of B16F10 cells was observed by in vivo imaging. RESULTS: CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1, claudin-5, occludin, P-gp, TNF-α, AQP4 and PDGFRß. In the behavioral tests, the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal. Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice. CR treatment significantly increased the levels of CD86, CD206, IL-4 and IL-10 and decreased the levels of CD163 and IL-1ß in the microenvironment of brain metastases. The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone. CONCLUSION: CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier, and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.

[Isolation and characterization of normal mandibular periosteal stem cells from human and macaca mulatta and cross-species single-cell analysis].

Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

[The current situation of occupational health in the Internet industry and countermeasures].

As an important force in promoting the transformation and upgrading of the national economy, the occupational health of the Internet industry's employees has received widespread attention. This paper examines the current situation of occupational health risks and management in the Internet industry at home and abroad, and on this basis reveals the physical and mental health problems of Internet industry employees. Combining the existing regulations, policies and standard documents at home and abroad, countermeasures are proposed to improve the relevant laws and regulations and their guidelines, implement relevant job design requirements, build a healthy working environment, optimise the work management system and carry out workplace health promotion, in order to provide ideas to accelerate the improvement of occupational health issues in the Internet industry.

[Xuezheng Quanji, the earliest monograph on blood disorder].

Xuezheng Quanji(«¼) written by Sun Guangyu, a doctor in the Ming Dynasty, is the first known book on blood disorders in China. The book mainly deals with bleeding. The book begins with a collection of the Neijing and the treatises of the sages, focusing on systematically summarizing the theories and experiences of the past dynasties in the treatment of bleeding, interspersed with Sun's own opinions.The main part discusses four types of bleeding, summarizing Sun's profound experience in clinical practice, and many of his personal creative opinions.In terms of causes,Sun believed that there are three causes of bleeding and more due to heat. In terms of treatment,he opposed the abuse of bitter cold and attached great importance to nourishing yin and strengthening kidney and proposed four treatment methods of dispelling stasis, nourishing Yin and suppressing Yang, regulating Qi and blood, and tonifying deficiency. He advocated that bleeding should not be treated quickly, and emphasized that the disease should be judged according to the bleeding location and bleeding color to use herbs flexibly.Special attention should be paid to daily life care during and after illness as well.

Acute rapamycin treatment reveals novel mechanisms of behavioral, physiological, and functional dysfunction in a maternal inflammation mouse model of autism and sensory over-responsivity.

Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and neuro-inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that might be expected to alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction and related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, and repetitive behaviors and sensory over-responsivity in adult offspring with persistent brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-,ion channel-, and epilepsy-associated genes, in the same time frame. Our findings suggest that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction, including neuronal excitability, altered gene expression in multiple cell types, sensory functional network connectivity, and modulation of information flow. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD behaviors in adult animals without requiring long-term physical alterations to the brain. Thus, restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing both primary sensory and social behavior phenotypes, and compensatory repetitive behavior phenotypes.

[Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3].

Objective: To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3). Methods: This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands. Results: A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion: Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

Night shift work and myocardial infarction in the UK Biobank.

BACKGROUND: Shift work has become popular along with adverse effects such as disrupted biological rhythms, metabolic changes, sleep disorders and myocardial infarction. Studies have shown a link between myocardial infarction and shift work, but evidence is still lacking. AIMS: We aim to explore the association between present and past shift work and risk of myocardial infarction in a large population of European workers. METHODS: We analysed data from the UK Biobank with >500 000 participants and an average 12-year follow-up duration. Cox proportional hazard models were employed to analyse the relationship between present shift work (n = 265 064), lifetime duration or frequency of shift work (n = 71 428) and the risk of myocardial infarction, as well as the association between rest day during shift work and myocardial infarction incidents in night shift workers (n = 14 588). RESULTS: Night shift workers had a higher risk of myocardial infarction compared to day workers, including 'shift but never/rarely night shifts' (hazard ratio [HR] = 1.09, 95% confidence interval [CI] 1.00-1.20), 'some night shifts' (HR = 1.13, 95% CI 1.01-1.27) and 'usual/permanent night shifts' (HR = 1.21, 95% CI 1.07-1.37), respectively. Similarly, higher frequency and longer duration of night shift work were associated with the increased risk of myocardial infarction (<10 years: HR = 1.20, 95% CI 1.01-1.42; ≥10 years: HR = 1.51, 95% CI 1.28-1.77; or an average of more than eight nights per month: HR = 1.45, 95% CI 1.23-1.71). However, longer rest days couldn't decrease myocardial infarction risk compared to those who rest 1 day. CONCLUSIONS: Present and lifetime exposure to night shifts were associated with a risk of myocardial infarction and did not benefit from longer rest days.

Outcomes and Relapse Patterns in Primary Central Nervous System Lymphoma: Longitudinal Analysis of 559 Patients Diagnosed From 1983-2020.

BACKGROUND: Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow up. METHODS: T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983-2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, other. Progression-free (PFS) and overall (OS) survival was assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. RESULTS: Median follow-up was 7.4 years (N=559). Most (321, 57%) were recursive partitioning analysis class 2 (age≥50, KPS≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs. PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5-years for 351 patients with CR/CRu to consolidation was 80% (95%CI:76-84%) and 46% (95%CI:41-53%), respectively; 1-year cumulative incidence of local vs non-local relapse was 1.8% vs 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local vs non-local relapse was 57% vs 42%, respectively. Deep structure involvement (HR 1.89, 95%CI:1.10-3.27) was associated with local relapse in refractory patients. CONCLUSIONS: We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.

[Conjecture on the next development direction of colorectal cancer and its minimally invasive surgery].

The surgical treatment of colorectal cancer will be more and more accurate and minimally invasive under the guidance of precision medicine. At the same time, it will derive and evolve non-surgical paths, such as immune checkpoint inhibitors and immune targeted therapy for microsatellite instability high/mismatch repair deficient colorectal cancer, and wait and watch path after neoadjuvant treatment for low advanced rectal cancer. Laparoscopic minimally invasive surgery for colorectal cancer will be gradually iterated by robots, which is the only way to intelligent surgery.

[Analysis of the effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture].

Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[COVID-19 and autoimmune dysregulation: exploring common mechanisms and treatment strategies in interstitial lung disease].

COVID-19 is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and manifests primarily as acute lung injury with diffuse interstitial lung disease evident in imaging. Patients often present with clinical features similar to those of autoimmune diseases and share imaging, treatment and serological similarities with autoimmune-related interstitial lung diseases. The association between autoimmune abnormalities and post-COVID-19 pulmonary fibrosis is also recognized. This article provided a comprehensive review of the pathogenic mechanisms, clinical manifestations, and therapeutic interventions associated with autoimmune abnormalities induced by SARS-CoV-2 infection.

Bromocriptine sensitivity in bromocriptine-induced drug-resistant prolactinomas is restored by inhibiting FGF19/FGFR4/PRL.

PURPOSE: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment. METHODS: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice. RESULTS: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels. CONCLUSION: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.

[Prediction model related to 6-year risk of frailty in older adults aged 65 years or above in China].

Objective: To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis. Results: The M(Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions: The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

[Analysis of loss to follow-up status and influencing factors of children born to pregnant women with HIV infection in China in 2019].

Objective: To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019. Methods: The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results: The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (aOR=0.34, 95%CI: 0.22-0.53), unmarried (aOR=0.47, 95%CI: 0.24-0.93), first marriage (aOR=0.38, 95%CI: 0.22-0.67), remarriage (aOR=0.36, 95%CI: 0.20-0.67) and cohabiting (aOR=0.47, 95%CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (aOR=0.53, 95%CI: 0.40-0.70) was lower. Han nationality (aOR=1.52, 95%CI: 1.09-2.13), primary school (aOR=2.06, 95%CI: 1.10-3.89) and junior middle school (aOR=1.81, 95%CI: 1.03-3.17) educational level, non-use of antiviral drugs (aOR=6.21, 95%CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (aOR=5.72, 95%CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions: HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.

Effects of different mesh materials on complications after prophylactic placement for stoma formation: a systematic review and network meta-analysis.

PURPOSE: We primary aimed to synthesise the available data, assess the effectiveness of different mesh materials in prophylactic mesh placement, and rank these materials according to the incidence of parastomal hernia (PSH) and other stoma complications. METHOD: This network meta-analysis performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Four databases were searched for randomised controlled trials of prophylactic mesh placement. The aggregated results were performed in the STATA routine for Bayesian hierarchical random effects models. RESULT: Thirteen randomised controlled trials from 1203 articles, met the inclusion criteria, including 681 cases without meshes, 65 cases with mesh material of xenogeneic acellular dermis (porcine/bovine), 27 cases with polypropylene/PG910, 114 cases with polypropylene/polyglecaprone (Monocryl), 117 cases with polypropylene/cellulose (ORC), 233 cases with polypropylene, and 35 cases with polypropylene/PVDF. In network A, compared with no mesh, only polypropylene (RR 0.24, 95% CI 0.04-0.80) were significantly associated with a reduction in the incidence of PSH. In network B, no statistical difference regarding stoma complications was found between mesh and no mesh. CONCLUSION: Based on the network meta-analysis and ranking results, the polypropylene mesh material exhibited the best performance. However, this conclusion needs to be confirmed with larger sample sizes and high-quality randomised controlled trials.

Palbociclib combined with endocrine treatment in hormone receptor-positive, HER2-negative breast cancer patients with high relapse risk after neoadjuvant chemotherapy: subgroup analyses of premenopausal patients in PENELOPE-B.

BACKGROUND: The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC at high risk of relapse [defined as no pathological complete response after neoadjuvant chemotherapy and a clinical, pathological stage, estrogen receptor, grading (CPS-EG) score ≥3 or 2/ypN+] were randomized to receive 13 cycles of palbociclib or placebo + standard ET. Ovarian function (OF) was evaluated by centrally assessed estradiol, follicle-stimulating hormone and anti-Müllerian hormone serum levels. RESULTS: Overall, 616 of 1250 randomized patients were premenopausal; of these, 30.0% were <40 years of age, 47.4% had four or more metastatic lymph nodes, and 58.2% had a CPS-EG score ≥3. 66.1% of patients were treated with tamoxifen alone, and 32.9% received ovarian function suppression (OFS) in addition to either tamoxifen or aromatase inhibitor (AI). After a median follow-up of 42.8 months (97.2% completeness) no difference in iDFS between palbociclib and placebo was observed [hazard ratio = 0.95, 95% confidence interval (CI) 0.69-1.30, P = 0.737]. The estimated 3-year iDFS rate was marginally higher in the palbociclib arm (80.6% versus 78.3%). Three year iDFS was higher in patients receiving AI than tamoxifen plus OFS or tamoxifen alone (86.0% versus 78.6% versus 78.0%). Patients receiving tamoxifen plus OFS showed a favorable iDFS with palbociclib (83.0% versus 74.1%, hazard ratio = 0.52, 95% CI 0.27-1.02, P = 0.057). Hematologic adverse events were more frequent with palbociclib (76.1% versus 1.9% grade 3-4, P < 0.001). Palbociclib seems not to negatively impact the OF throughout the treatment period. CONCLUSIONS: In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period.

[Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease].

OBJECTIVE: To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's disease (PD) via the gut-brain axis. METHODS: Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group, PD model group, and NaB treatment group. In the latter two groups, PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) once daily for 5 consecutive days, and normal saline was injected in the control group. After modeling, the mice received daily gavage of NaB (300 mg/kg) or an equal volume of saline for 14 days. Behavioral tests were carried out to assess the changes in motor function of the mice, and Western blotting was performed to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the striatum and nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the tight junction proteins ZO-1, Occludin, and Claudinin the colon. HE staining was used to observe inflammatory cell infiltration in the colon of the mice. RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues, and their expressions were verified using qRT-PCR and Western blotting. RESULTS: The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH, Occludin, and Claudin and downregulated expressions of α-syn, NF-κB, TNF-α, and IL-6 (all P < 0.05). HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice. RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice (P < 0.05). CONCLUSION: NaB can improve motor dysfunction, reduce dopaminergic neuron loss in the striatum, and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.