[Introduction to Guidelines for public health protection against high temperature and heatwaves].

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world].

Objective: To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . Methods: From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. Results: ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions: There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

[A case of nontuberculous mycobacterium presenting as a mass and atelectasis with mediastinal and hilar lymph node enlargement].

With the development of testing technology, the diagnosis of nontuberculous mycobacterium (NTM) lung disease has gradually increased in recent years. Because the clinical characteristics of NTM are not typical, and its imaging manifestations are diverse and nonspecific, missed diagnosis and misdiagnosis are common. Etiological investigation is necessary for diagnosis. Conventional etiological investigations are very limited for the diagnosis of NTM. We reported a case of NTM lung disease presenting with a mass and atelectasis with mediastinal and hilar lymph node enlargement that resembled malignant tumors. The literature on this condition was reviewed to improve the clinician's understanding and broaden clinical thinking.

Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers.

BACKGROUND: Primary syphilis is characterized by painless ulcerative lesions in the genitalia, the aetiology of painless remains elusive. OBJECTIVES: To investigate the role of Treponema pallidum in painless ulcer of primary syphilis, and the mechanisms underlying painless ulcers caused by T. pallidum. METHODS: An experimental rabbit model of primary syphilis was established to investigate its effects on peripheral nerve tissues. Human skin fibroblasts were used to examine the role of T. pallidum in modulating neurotransmitters associated with pain and to explore the signalling pathways related to neurotransmitter secretion by T. pallidum in vitro. RESULTS: Treponema pallidum infection did not directly lead to neuronal damage or interfere with the neuronal resting potential. Instead, it facilitated the secretion of prostaglandin E2 (PGE2) through endoplasmic reticulum stress in both rabbit and human skin fibroblasts, and upregulation of PGE2 induced the hyperpolarization of neurones. Moreover, the IRE1α/COX-2 signalling pathway was identified as the underlying mechanism by which T. pallidum induced the production of PGE2 in human skin fibroblasts. CONCLUSION: Treponema pallidum promotes PGE2 secretion in skin fibroblasts, leading to the excitation of neuronal hyperpolarization and potentially contributing to the pathogenesis of painless ulcers in syphilis.

[Analysis of gut target microbiota and species difference in patients with obstructive sleep apnea based on 16S rRNA sequencing].

OBJECTIVE: To explore the difference in gut microbiota composition between patients with obstructive sleep apnea (OSA) and healthy individuals and the role of gut microbiota in the pathogenesis of OSA. METHODS: Thirty-nine patients with OSA admitted to our hospital between May and December, 2022 and 20 healthy individuals were enrolled in this study. Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high- throughput sequencing analysis. The alpha diversity, beta diversity, and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed. RESULTS: The species diversity (Shannon and Simpson) indexes, richness (observed species) and evenness (Pielou) of gut microbiota were significantly lower in OSA patients than in the healthy individuals (P < 0.05). The OSA patients had also a significantly lowered community diversity (P < 0.05) with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes (P < 0.05). LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas, Meganomonas, and Fusobacterium (P < 0.05). The differential marker flora affected host homeostasis. Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis. Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis, and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway. CONCLUSION: OSA patients have obvious gut microbiota disturbances, and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Prenatal exposure to PM2.5 components and the risk of different types of preterm birth and the mediating effect of pregnancy complications: a cohort study.

OBJECTIVES: This study aims to reveal the single and mixed associations of PM2.5 and its components with very, moderately, and late preterm births and to explore the potential mediating role of pregnancy complications in PM2.5-induced preterm birth. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 168,852 mothers and matched the concentrations of PM2.5 and its five components (OM, SO42-, BC, NO3-, and NH4+) based on their geographical location. Next, we used generalized linear models, quantile g-computation, and mediation analysis to evaluate the associations of PM2.5 and its components with very, moderately, and late preterm births and the mediating role of pregnancy complications. RESULTS: Prenatal exposure to PM2.5 and its components was associated with preterm birth, and the association was strongest in the third trimester. Preterm birth was associated with co-exposure to a mixture of PM2.5 components in the third trimester, and the contributions of NO3-, NH4+, and BC to the risk of preterm birth were positive. Meanwhile, pregnancy complications mediated PM2.5-induced preterm birth. Moreover, very and moderately preterm births were associated with PM2.5 and its components in the second and third trimesters, and very and late preterm births were associated with co-exposure to a mixture of PM2.5 components in the third trimester. CONCLUSIONS: Later exposure to PM2.5 during pregnancy will cause earlier preterm birth. Targeted and positive interventions for anthropogenic sources of specific PM2.5 components and pregnancy complications are helpful for preterm birth prevention.

[Progress and practice of objective measurement of physical behaviors in large-scale cohort research].

Due to the limited reliability of traditional self-completed questionnaire, the accuracy of measurement of physical behaviors (physical activity, sedentary behavior and sleep) is not high. With the development of technology, wearable devices (e.g. accelerometer) can be used for more accurate measurement of physical behaviors and have great application potential in large-scale research. However, the data of objective measurement of physical behaviors from large-scale cohort research in Asian populations is still limited. Between August 2020 and December 2021, the 3rd resurvey of China Kadoorie Biobank (CKB) project used Axivity AX3 wrist triaxial accelerometer to collect the data of participants' daily activity and sleep status. A total of 20 370 participants from 10 study areas were included in the study, in whom 65.2% were women, and the age was (65.4±9.1) years. The participants' physical activity level varied greatly in different study areas. The objective measurement of participants' physical behaviors in CKB project has provided valuable resources for the description of 24-hour patterns of physical behaviors and evaluation of the health effect of physical activity, sedentary behavior and sleep as well as their association with diseases in the elderly in China.

Prediction of Fuhrman grade of renal clear cell carcinoma by multimodal MRI radiomics: a retrospective study.

AIM: To explore the value of multimodal magnetic resonance imaging (MRI) radiomics combined with traditional radiologist-defined semantic characteristics and conventional (cMRI) and functional MRI (fMRI) texture features in predicting Fuhrman grade of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The data of 89 patients with histopathologically proven ccRCC (low-grade, 54; high-grade, 35) were collected. Texture features were extracted from cMRI (T1- and T2-weighted imaging) and fMRI (Dixon-MRI; blood-oxygen-level dependent [BOLD]-MRI; and susceptibility-weighted imaging [SWI]) images, and the traditional characteristics (TC) were evaluated. Logistic regression analysis was performed to develop models based on TC, cMRI, and fMRI texture features for grading. Receiver operating characteristic (ROC) curve analysis and leave-group-out cross-validation (LGOCV) were performed to test the reliability of combined models. RESULTS: Two T2-weighted imaging-based, two Dixon_W-based, one Dixon_F-based, one BOLD-based, and three SWI-based texture features, and three TC were extracted for feature selection. TC, cMRI, fMRI, cMRI+fMRI, cMRI+TC, fMRI+TC, and cMRI+fMRI+TC models were constructed. The AUC of the cMRI+fMRI+TC model for differentiating high- from low-grade ccRCC was 0.74, with 81.42% accuracy, 75.93% sensitivity, and 91.43% specificity. The fMRI+TC model exhibited a performance similar to that of the cMRI+fMRI+TC model (p>0.05). The areas under the curve (AUCs) of the fMRI+TC and cMRI+fMRI+TC models were significantly higher than those of the other five models (all p<0.05). For the cMRI+fMRI+TC model, the mean accuracy was 85.40% after 100 LGOCV for the test sets. CONCLUSION: Multimodal MRI radiomics combined with TC, cMRI, and fMRI texture features may be a reliable quantitative approach for differentiating high-grade ccRCC from low-grade ccRCC.

Impaired local Vitamin D3 metabolism contributes to IL-36g overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.

Belimumab therapy for refractory immune thrombocytopenia in systemic lupus erythematosus patients with anti-phospholipid antibodies.

OBJECTIVE: To observe the effect of belimumab treatment in refractory anti-phospholipid antibody-associated immune thrombocytopenia with systemic lupus erythematosus (SLE). METHOD: Four SLE patients with refractory anti-phospholipid antibody-associated immune thrombocytopenia were included in this one-arm observational study. Inclusion criteria were a diagnosis of SLE according to 1997 American College of Rheumatology criteria, severe immune thrombocytopenia (platelets <30 × 109/L), no bleeding symptoms, lack of satisfactory response to traditional treatment, and high-titre anti-phospholipid antibodies. All patients received belimumab (Benlysta®) for 6 months. RESULTS: The mean platelet count was 21.8 × 109 cells/L, ranging between 16 and 29 × 109/L at baseline, 123.3 × 109/L at 1 month, and 172.5 × 109/L at the end of 6 months after belimumab treatment. No bleeding complications occurred during the entire follow-up period. CONCLUSION: In this study, belimumab reduced the anti-phospholipid antibodies while increasing the platelet count in SLE patients with anti-phospholipid antibody-associated immune thrombocytopenia.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Research progress on Mycobacterium tuberculosis acetyltransferase].

The protein acetylation of Mycobacterium tuberculosis(MTB) plays an important role in virulence, drug resistance, regulation of metabolism and host anti-tuberculosis immune response. The proteins acetylation of MTB and host protein could be induced by the MTB acetyltransferase, which is related to the occurrence, development and prognosis of tuberculosis (TB). A clear understanding of the function of MTB acetyltransferase and identification of its targeted regulatory protein acetylation modification is critical to elucidate the pathogenic mechanism and drug resistance mechanism of TB, and then this could then provide new targets for the development of anti-tuberculosis drugs. This article systematically reviewed the research progress on MTB acetyltransferase related functions, which will provide a theoretical basis for further research on its mediated protein acetylation modification, further development of new anti-tuberculosis drugs and elucidation of drug resistance mechanism.

[Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage â ovarian immature teratoma after fertility-sparing surgery].

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

[Predictive value of net water uptake with respect to early neurological improvement after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke].

Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio (OR)=0.940, 95% confidence interval (CI) 0.903-0.979, P=0.003], time from stroke onset to puncture (OR=0.995, 95%CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation (OR=0.985, 95%CI 0.974-0.996, P=0.007), NWU (OR=0.762, 95%CI 0.620-0.937, P=0.010), and mTICI (OR=1.644, 95%CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95%CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.

[Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix].

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice].

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) µg/mg vs. (0.974±0.060) µg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) µg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.