[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

[High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-ß signaling pathway].

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.

Water uptake patterns and rooting depths of Tamarix ramosissima in the coppice dunes of the Gurbantünggüt Desert, China: a stable isotope analysis.

Tamarix ramosissima has an important role in stabilizing sand dunes in desert ecosystems. Understanding the water use strategies of T. ramosissima is essential to understand its adaptations on coppice dunes. We utilized the stable isotopes δ2H and δ18O in soil water, groundwater, and xylem water to identify monthly differences in water sources. Additionally. we explored rooting depth using 2H2O as an artificial tracer. In May, T. ramosissima derived 75% of its water from shallow and middle soil layers. In July, it absorbed 90% water from middle and deep soil layers. In August and September, it acquired approximately 80% of its water from deep soil layers. The labelling using 2H as an artificial tracer indicated that the root system of T. ramosissima could reach depths >500 cm in the coppice dunes. 2H absorption was observed at depths of 100, 200, 300 and 400 cm. Soil water is the dominant water source for T. ramosissima in the coppice dunes because groundwater is at depths >30 m. The flexible water-use strategies of T. ramosissima enable it to effectively utilize different available water sources to adapt to the arid environment. These findings improve our understanding of water uptake patterns and drought adaptation strategies of T. ramosissima in the coppice dunes of desert ecosystems.

In situ evidence of the magnetospheric cusp of Jupiter from Juno spacecraft measurements.

The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter's rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures.

[How do female mosquitoes determine the most suitable males for mating?]

More than 80% of the world's populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

[Comparison of quantitative detection of BCR::ABL1 p210 transcript levels: a multicenter study].

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

[Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp].

Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

[Standardized diagnosis and treatment of colorectal polyps].

This article explores the standardized management of colorectal polyps, including classification, treatment, follow-up, and preventive control. Corresponding treatment strategies, including endoscopic resection and surgical intervention, are employed for different types of polyps. Currently, there is debate over whether to choose endoscopic resection or surgical intervention for malignant polyps at pT1 stage. Drawing on the latest literature and guidelines, the article elaborates on polyp classification, treatment modalities, follow-up, and preventive measures. Standardized management of colorectal polyps is important for reducing the incidence of colorectal cancer and improving the cure rate of early-stage colorectal cancer.

[Primary mucinous gland lesions of fallopian tube: a clinicopathological analysis of fourteen cases].

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.

[Epidemiological investigation and risk factors of diabetic retinopathy in Yunnan Province].

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A1c (HbA1c)≥7.0% was the risk factor of mild-NPDR (OR=1.872, 95%CI 1.055-3.323) and RDR (OR=4.821, 95%CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR (OR=1.933, 95%CI 1.112-3.358) and RDR (OR=1.505, 95%CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

[To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability].

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

Independent and combined effects of smoking, drinking and depression on periodontal disease.

BACKGROUND: Periodontitis is a complex chronic inflammatory disease that is particularly associated with health-related conditions such as smoking, excessive drinking and depression. This research aimed to investigate the interaction between these lifestyles factors on periodontitis risk. METHODS: This study included participants who participated in the National Health and Nutrition Examination Survey in the United States between 2009 and 2014. They had completed oral health-periodontal examination, Smoking-Cigarette Use Questionnaire, Alcohol Use Questionnaire, and Patient Health Questionnaire. Periodontal clinical attachment loss (CAL) of 3 mm or more and Patient Health Questionnaire-9 (PHQ-9) of 10 scores or more were used to identify periodontitis and depression, respectively. Daily alcohol consumption in the past year was classified into three levels: low (1 drink or less), moderate (between 1 and 3 drinks), and heavy drinking (4 drinks or more), while smoking was defined as having smoked at least 100 cigarettes in one's lifetime. Then, the logistic regression combined with interaction models were used to analyze the independent and combined effects of smoking, drinking and depression on periodontitis risk. RESULTS: The results indicated a statistically significant multiplicative interaction between smoking and depression in relation to the development of periodontitis, both in the overall population (P = 0.03) and among male participants (P = 0.03). Furthermore, among individuals experiencing depression, smoking was found to significantly increase the prevalence of periodontitis by 129% in the younger age group compared to non-smokers (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.10 to 4.76). However, the interaction between smoking and alcohol consumption was only significant among females (P < 0.05). There was a dose-dependent relationship between drinking frequency and smoking on periodontitis prevalence. In the smoking population, occasional drinking (OR: 1.70; 95% CI: 1.22 to 2.37) and regular drinking (OR: 2.28; 95% CI: 1.68 to 3.11) significantly increased the prevalence of periodontitis compared to individuals without these two factors. CONCLUSION: These results suggested that there were interactive effects between smoking, drinking and depression on periodontitis risk and policies aimed at healthy behaviours and mental health may be beneficial for our oral health.

[Efficacy and safety of venetoclax combined with hypomethylating agents in the treatment of 83 patients with higher-risk myelodysplastic syndromes].

Objective: This study aimed to evaluate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of higher-risk myelodysplastic syndromes (HR-MDS) and analyze the factors influencing their therapeutic effect. Methods: The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed. All patients were treated with VEN combined with HMA. The Kaplan-Meier method was used to depict the survival curves, and the log-rank test was used to compare survival between the groups. Results: The median age was 57 (15-82) years old, and 51 patients (61.4%) were male. Forty-five patients (54.2%) were initially treated with HMA, 23 (27.7%) received ≤4 cycles of HMA, and 15 (18.1%) demonstrated HMA failure. At the median follow-up of 10.3 (0.6-34.4) months, the overall response rate (ORR) was 62.7% (52/83), including 18 patients (21.7%) with a complete response (CR), 14 (16.9%) with a bone marrow CR (mCR) with hematological improvement, and 20 (24.1%) with a mCR. The ORR of patients with initial treatment, ≤4 HMA cycles, and HMA failure were 66.7%, 60.9%, and 53.3%, respectively (P=0.641). The median overall survival time was 14.6 (95% CI 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% CI 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% CI 3.036-69.951, P=0.001), TP53 mutation (OR=13.052, 95% CI 1.982-85.932, P=0.008), and U2AF1 mutation (OR=7.720, 95% CI 1.540-38.698, P=0.013) were independent risk factors for poor efficacy of VEN combined with HMA. Hematological toxicity occurred in all patients, and the incidence of treatment-induced grade 3-4 leukopenia was 48.2% (40/83). Infection was the most common non-hematological adverse event, mainly pulmonary infection (31.3%) . Conclusion: VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.

[Exploration and contemplation of homogenized education of specialists in pulmonary and critical care medicine at member hospitals of a hospital consortium].

Talent construction is the cornerstone to the establishment of a high-quality, homogeneous healthcare system in a healthcare consortium. Pulmonary and critical care medicine (PCCM) as the first pilot specialty, the standardized training of PCCM specialists has started and achieved remarkable results. The consortium member hospitals' physician specialist education is an important complement to PCCM training. The establishment of the consortium provides a new form of the education of physicians in PCCM, with the advantages of high quality teaching, wide coverage of staff and throughout the career development process. This article summarized the current status of physician specialty education in the member hospitals of the consortium, and further proposes the goal of homogenized specialty education for physicians in the member hospitals. And it analyzed in depth the problems that existed in the practice of training for hospital consortium member hospitals specialists, such as non-uniform level of instruction, non-systematic content of training, limited sources of teaching cases, and lack of teaching materials and equipment. For the medical consortium member hospital physician specialty education of in-depth thinking, we put forward the corresponding countermeasures. The aim of this study is to explore the homogenization of the specialty education system of pulmonary and critical care medicine in the member hospitals, in order to comprehensively improve the medical level of respiratory specialists in the member hospitals of the medical consortium.

The role of microstructure in the thermal fatigue of solder joints.

Thermal fatigue is a common failure mode in electronic solder joints, yet the role of microstructure is incompletely understood. Here, we quantify the evolution of microstructure and damage in Sn-3Ag-0.5Cu joints throughout a ball grid array (BGA) package using EBSD mapping of localised subgrains, recrystallisation and heavily coarsened Ag3Sn. We then interpret the results with a multi-scale modelling approach that links from a continuum model at the package/board scale through to a crystal plasticity finite element model at the microstructure scale. We measure and explain the dependence of damage evolution on (i) the ß-Sn crystal orientation(s) in single and multigrain joints, and (ii) the coefficient of thermal expansion (CTE) mismatch between tin grains in cyclic twinned multigrain joints. We further explore the relative importance of the solder microstructure versus the joint location in the array. The results provide a basis for designing optimum solder joint microstructures for thermal fatigue resistance.