[Application of 21-gene recurrence risk score in patients with breast cancer].

Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

[Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing].

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) µm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) µm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

[Efficacy and safety analysis of P-GemDOx regimen and stratified prognosis in patients with early extranodal NK/T cell lymphoma].

Objective: To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . Methods: A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. Results: After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (P<0.001) between the POD<24 group (n=14) and the POD≥24 group (n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion: This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

[Therapeutic strategy for totally thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation].

Objective: To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass. Methods: This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People's Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period. Results: The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of (M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation (OR=11.424, 95%CI: 1.477 to 144.564, P=0.033) and excessive rewarming (OR=15.249, 95%CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions: The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

[Research progress of vaccination status, efficacy and safety in children with tumor].

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

Osteoporosis is associated with depression among older adults: a nationwide population-based study in the USA from 2005 to 2020.

OBJECTIVES: The global prevalence of osteoporosis is rising, yet it is unclear whether people with osteoporosis have a higher risk of depression than those without osteoporosis. STUDY DESIGN: A cross-sectional study. METHODS: We used nationally representative data from the US National Health and Nutrition Examination Survey (NHANES) in 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2020. The diagnosis of osteoporosis was based on the bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a score ≥5 as depressive symptoms and a score ≥10 as probable depression. We used logistic regression models to evaluate the association between osteoporosis and depressive symptoms and probable depression. RESULTS: We included 11,603 adults (aged 50 years and older, 52.3% male) and observed 5.2% of them had osteoporosis. 31.9% of these osteoporotic people had depressive symptoms, and 10.0% had probable depression. Compared to participants without osteoporosis, those with osteoporosis were 1.73 times more likely to experience depressive symptoms (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.20-2.50) and 1.91 times more likely to experience probable depression (OR = 1.91, 95% CI 1.02-3.59), after adjusting for sex, age, race/ethnicity, education, marital status, family income, body mass index, smoking, physical activity, and alcohol abuse. Moderate-to-vigorous activities mediated the associations between osteoporosis and depression and depressive symptoms. CONCLUSIONS: Osteoporosis is an independent risk factor for depression. This study highlights the need to evaluate the mental well-being of patients with osteoporosis in clinical and primary health care.

[Research progress on health hazards of oil mist].

Metal working fluidis widely used as coolant, lubricant and rust remover in mechanical processing. Oil mist will be formed in the process of metal working fluid. The composition of oil mist is complex, which can produce many adverse effects on the environment and operators. This paper reviews the health hazards of metal working fluid oil mist on human skin, respiratory system, teratogenic and carcinogenic aspects, and discusses the establishment of occupational exposure limits in workplaces of oil mist in foreign countries, in order to provide reference for the prevention and control of occupational health risks of metal working fluid oil mist and the establishment of occupational exposure limits of oil mist in workplaces in China.

[Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma].

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

[Influencing factors of futile recanalization after endovascular therapy in acute ischemic stroke patients with large vessel occlusions].

Objective: To analyze the influencing factors of futile recanalization after endovascular therapy (EVT) in acute ischemic stroke patients with large vessel occlusions (AIS-LVO). Methods: AIS-LVO patients who underwent EVT with successful recanalization between January 2019 and December 2021 in Neurovascular Center of Changhai Hospital of Naval Medical University were retrospectively selected. Modified Rankin scale (mRS) score 3 months after EVT was used as the prognostic evaluation index, and patients with mRS scores≤2 were classified as the meaningful recanalization group and mRS scores 3-6 as the futile recanalization group. The risk factors, National Institutes of Health stroke scale (NIHSS) score, Glasgow coma scale (GCS) score, Alberta Stroke Program Early CT (ASPECT) score, core infarct volume, etc. in both groups were analyzed, and the influencing factors of futile recanalization after EVT were analyzed by multivariate logistic regression. Continuous variables that do not conform to the normal distribution are represented by [M(Q1,Q3)]. Results: A total of 368 patients meeting the inclusion criteria were collected, including 228 males and 140 females, and aged 68 (61, 77) years. There are 196 patients and 172 patients in the meaningful recanalization and futile recanalization groups, respectively, with the rate of futile recanalization 3 months after EVT of 46.74% (172/368). Comparing the general information and risk factors between the two groups found that the age of patients in the futile recanalization group [71 (65, 79) years] was higher than that in the meaningful recanalization group [65 (59, 72) years]. The baseline NIHSS score [18 (14, 22)] and the rate of not achieving modified Thrombolysis in Cerebral Ischemia grade 3 (mTICI 3) reperfusion (36.1%) were higher in the futile recanalization group than those in the meaningful recanalization group [12 (7, 17) and 19.9%]. The baseline GCS score [11 (9, 13)] was lower in the futile recanalization group than that in the meaningful recanalization group [14 (11, 15)]. The core infarct volume in the futile recanalization group [28 (7, 65) ml] was larger than that in the meaningful recanalization group [6 (0, 17) ml]. The ASPECT score [7 (5, 9)] was lower in the futile recanalization group than that in the meaningful recanalization group [9 (7, 10)]. In addition, the proportion of hypertension, atrial fibrillation, general anesthesia, and symptomatic intracranial hemorrhage was higher in the futile recanalization group (all P<0.05). The time from symptom onset to puncture and from symptom onset to reperfusion was longer in the futile recanalization group (both P<0.05). There were statistically significant differences in trial of Org 10172 in acute stroke treatment (TOAST) classification and the site of occluded blood vessels between the two groups (both P<0.05). Multivariate logistic regression indicated that age ≥80 years(OR=1.935,95%CI: 1.168-3.205), baseline NIHSS score (OR=1.999,95%CI: 1.202-3.325), GCS score (OR=2.299,95%CI: 1.386-3.814), previous stroke history (OR=1.977,95%CI: 1.085-3.604), general anesthesia (OR=1.981,95%CI: 1.143-3.435), not achieving grade 3 recanalization (OR=2.846, 95%CI: 1.575-5.143), ASPECT score<6 (OR=2.616, 95%CI: 1.168-5.857), and core infarct volume>70 ml (OR=2.712, 95%CI: 1.130-6.505) were risk factors for futile recanalization. Conclusion: Age≥80 years, previous stroke history, baseline NIHSS score≥20, GCS score≤8, general anesthesia, ASPECT score<6, core infarct volume>70 ml, and failure to achieve Grade 3 recanalization are independent influencing factors for futile recanalization after endovascular therapy in AIS-LVO patients.

[Association between chronic lung diseases and the risk of lung cancer in UK Biobank: observational and Mendelian randomization analyses].

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q1, Q3)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.

[Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians].

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

[Review and perspective of clinical research involving chest tightness variant asthma in China].

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.

[Characteristics of serum bile acids among healthy children in Zhejiang province].

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Meta-analysis of InterTan, PFNA and PFNA-II internal fixation for the treatment of unstable intertrochanteric fractures in elderly individuals.

Elderly individuals are often affected by osteoporosis and have poor stability after fracture reduction. Moreover, there is still controversy regarding the clinical effects of the treatment for unstable intertrochanteric fractures in the elderly. The Cochrane, Embase, PubMed, and other databases were searched, and a meta-analysis of the literature on the treatment of unstable intertrochanteric fractures of the elderly with InterTan, PFNA, and PFNA-II was conducted. Seven studies were screened, with a total of 1236 patients. Our meta-analysis results show that InterTan is not significantly different from PFNA in terms of operation and fluoroscopy times, but it takes longer than PFNA-II. In terms of postoperative screw cut, pain, femoral shaft fracture, and secondary operations, InterTan is superior to PFNA and PFNA-II. Conversely, in terms of intraoperative blood loss, hospital stay, and postoperative Harris score, there is no significant difference between InterTan and PFNA and PFNA-II. Compared to PFNA and PFNA-II, InterTan internal fixation has advantages in the treatment of unstable intertrochanteric fractures in elderly individuals in terms of screw cutting, femoral shaft fractures, and secondary operations. However, InterTan operation and fluoroscopy times take longer than PFNA and PFNA-II.

[Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism].

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

[Identification and verification of α-11 giardin-interacting protein].

OBJECTIVE: To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. METHODS: The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). RESULTS: The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. CONCLUSIONS: The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

[Multi-omics approaches for revealing the etiology of cancer: from genomics, exposomics, metabolomics to system epidemiology].

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.