[Erdheim-Chester disease initially discovered at extraskeletal locations: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of Erdheim-Chester disease (ECD) initially diagnosed at extraskeletal locations. Methods: Clinical and pathological data of four cases of ECD diagnosed initially in extraskeletal locations were collected at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to June 2023. BRAF V600E gene was detected by reverse transcription polymerase chain reaction (RT-PCR). Pertinent literatures were reviewed. Results: Four ECD patients included two males and two females ranging in ages from 2 years 11 months to 69 years. The lesions located in the lung (two cases), central nervous system (one case), and the testicle (one case) were collected in the study. One patient had occasional fever at night, one had nausea and vomiting, and two were asymptomatic. Radiologically, the two pulmonary ECD showed diffuse ground-glass nodules in both lungs, and the lesions in central nervous system and testicle both showed solid masses. Microscopically, there were infiltration of foamy histiocyte-like cells and multinucleated giant cells in a fibrotic background, accompanied by varying amounts of lymphocytes and plasma cells. The infiltration of tumor cells in pulmonary ECD was mainly seen in the subpleural area, interlobular septa, and perivascular and peribronchiolar areas. The fibrosis was more pronounced in the pleura and interlobular septa, and less pronounced in the alveolar septa. Immunohistochemical staining showed that all tumor cells expressed CD68, CD163 and Fô€ƒ¼a; one case showed S-100 expression; three cases were positive for BRAF V600E; all were negative for CD1α and Langerin. RT-PCR in all four cases showed BRAF V600E gene mutation. Conclusions: Extraskeletal ECD is often rare and occult, and could be easily misdiagnosed, requiring biopsy confirmation. The radiologic findings of pulmonary ECD is significantly different from other types of ECD, and the histopathological features of pronounced infiltration in the subpleura area, interlobular septa, perivascular and peribronchiolar areas can be helpful in the differential diagnosis from other pulmonary diseases. Detection of BRAF V600E gene mutation by RT-PCR and its expression by immunohistochemical staining are also helpful in the diagnosis.

Considerations Around Structure-Based Drug Discovery for KRAS Using DOCK.

Molecular docking is a popular computational tool in drug discovery. Leveraging structural information, docking software predicts binding poses of small molecules to cavities on the surfaces of proteins. Virtual screening for ligand discovery is a useful application of docking software. In this chapter, using the enigmatic KRAS protein as an example system, we endeavor to teach the reader about best practices for performing molecular docking with UCSF DOCK. We discuss methods for virtual screening and docking molecules on KRAS. We present the following six points to optimize our docking setup for prosecuting a virtual screen: protein structure choice, pocket selection, optimization of the scoring function, modification of sampling spheres and sampling procedures, choosing an appropriate portion of chemical space to dock, and the choice of which top scoring molecules to pick for purchase.

[Research progress on the cyclic GMP-AMP synthase stimulator of interferon genes pathway in respiratory diseases].

Cyclic GMP-AMP synthase (cGAS) is a DNA receptor that produces the second messenger cyclic GMP-AMP (cGAMP). cGAMP activates stimulator of interferon genes (STING), which initiates a signaling cascade leading to immune and inflammatory responses. This intricate molecular pathway plays a pivotal role in the pathogenesis and progression of diverse respiratory ailments, including respiratory infection, lung cancer, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, asthma, and acute lung injury. Consequently, the cGAS-STING signaling pathway has emerged as a promising novel therapeutic target, opening up new avenues for the diagnosis and treatment of respiratory disorders. This review focuses on recent advances in our understanding of the cGAS-STING signaling pathway and its intricate involvement in respiratory system diseases.

Comparing the clinical efficacy and safety of second-line targeted therapy and immunotherapy in patients with mid- to advanced stages of hepatocellular carcinoma - A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of second-line immunotherapy and targeted treatment in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From January 2000 to January 2023, ProQuest, PubMed, Web of Science, Scopus, Embase, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) using immunotherapy or targeted therapy as second-line therapy for mid-to-advanced stages of HCC. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) are all examples of measures of success. RESULTS: This analysis included twenty Randomized Clinical Trials (RCTs) from phases II and III. Collective data revealed better OS with immunotherapy (HR = 0.79; 95% CI: 0.67, 0.93 vs. 0.85; 95% CI: 0.78, 0.92), while the targeted therapy played a more effective role in PFS (0.67; 95% CI: 0.56, 0.81). Also, the second-line immunotherapy had a lower odds ratio of AEs of grades 3-5 than the targeted therapy did (OR = 1.75; 95% CI = 0.89, 3.46). CONCLUSIONS: Overall, it appears that targeted medication and immunotherapy as a second-line treatment strategy have generally improved substantially, as well as progression-free survival for patients with mid-to-advanced HCC. Although it is difficult to judge their efficiency, the occurrences of AEs were greater in targeted therapy compared to immunotherapy.

Suction rectal biopsy (SRB) in Hirschsprung's Disease: Is a single macroscopically adequate sample sufficient?

Hirschsprung's Disease (HD) is a congenital disorder causing severe constipation in infants and children. Suction rectal biopsy (SRB) is the preferred technique for obtaining tissue samples for histopathological evaluation. In low-resource settings like Malaysia, cost-effective diagnostic approaches are necessary, making single sample SRB valuable. This study evaluates the diagnostic accuracy and sufficiency of a single macroscopically adequate sample in suction rectal biopsies for the histopathological confirmation of HD. We conducted a retrospective study of children who underwent suction rectal biopsies for the diagnosis of HD at Hospital Raja Perempuan Zainab II (HRPZII), Kota Bharu, Kelantan. A total of 68 patients were included in the study. The inadequacy rate for bedside SRB was 14%, comparable to current literature. Our study found no statistically significant association between sample inadequacy and gestational age, gender, birth weight, or weight at biopsy. Complication rates were 0%, consistent with literature reports. Calretinin staining, an additional technique, was performed in 23 biopsy episodes, with a 4.3% inadequacy rate, compared to 20% in specimens not subjected to calretinin staining. The cost of SRB almost doubled with each additional sample taken, significant in low-resource environments. In conclusion, single sample SRBs can be adequately diagnostic and cost-effective in low-resource settings, providing valuable insights for healthcare facilities in Malaysia and other developing countries. The use of adjunctive techniques such as calretinin staining may improve diagnostic accuracy while maintaining cost-effectiveness. Further prospective studies with larger sample sizes are needed to validate these findings.

[Clinical study of antinib combined with radiotherapy in the treatment of third-line extensive small cell lung cancer].

Objective: To explore whether the survival benefit of the third-line extensive small-cell lung cancer (ES-SCLC) will be obtained by the combination of anlotinib and radiotherapy, and evaluate the safety of this treatment regimen. Methods: Twenty-seven patients with ES-SCLC who received third-line treatment with less than three metastatic organs at the Cancer Hospital of Xinjiang Medical University from November 2018 to July 2021 were collected and treated with radiotherapy based on anlotinib. Kaplan-Meier curve was used to estimate the overall survival (OS) and progression-free survival (PFS), descriptive statistical analysis was used to evaluate the safety, and European organisation for research and treatment of cancer quality of life questionnaire-core 30 (EORTC QLQ-C30) was used to evaluate the quality of life. Results: The follow-up cut-off date was July 1, 2021, and the follow-up time ranged from 4.8 to 31.0 months, with a median follow-up time of 10.2 months for the entire group. Among the 27 patients, 4 achieved partial remission, 17 had stable disease and 6 had progression of disease. The objective remission rate (ORR) was 14.8%, and the disease control rate (DCR) was 77.8%. Median PFS and the median OS were 5 months and 11 months, respectively. The most common adverse reactions included fatigue (33.3%, 9/27), anorexia (14.8%, 4/27), bleeding (14.8%, 4/27) and hand-foot syndrome (11.1%, 3/27). Most of them were grade 1 to grade 2, 3 cases were more than grade 3, and there was no grade 5 toxicity recorded. After radiotherapy combined with amlotinib treatment, patients showed improvement in general health, somatic functioning, social functioning, and emotional functioning (all P<0.05). Conclusion: For the third-line ES-SCLC patients, radiotherapy based on the anlotinib can significantly prolong their PFS and OS, and the adverse reactions can be tolerated.

[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

Readability and quality of online patient health information on parotidectomy.

OBJECTIVE: Complications of parotidectomy can have a massive impact on patients' quality of life. This study aimed to evaluate the readability and quality of online health information on parotidectomy. METHOD: The search terms 'parotidectomy', 'parotid surgery', 'parotidectomy patient information' and 'parotid surgery patient information' were parsed through three popular search engines. RESULTS: The websites were analysed using readability scores of the Flesch Reading Ease test and the Gunning Fog Index. The DISCERN instrument was used to assess quality and reliability. The average Flesch Reading Ease score was 50.2 ± 9.0, indicating that the materials were fairly difficult to read, the Gunning Fog Index score showed that the patient health information was suitable for an individual above 12th grade level, and the DISCERN score indicated that the online patient health information had fair quality. The Kruskal-Wallis test showed a significant difference in Flesch Reading Ease and DISCERN tool scores according to website category (p < 0.05). CONCLUSION: Current online patient health information on parotidectomy is too difficult for the public to understand, and it exceeds the reading levels recommended by Health Education England and the American Medical Association.

[Progress on development and application of the diet-related inflammatory index in cancer epidemiological studies].

Cancer is a major public health problem worldwide, causing an more serious burden of disease. Inflammation is considered a predisposing factor for cancer with close relationship with its incidence. In recent years, the public and epidemiologists has paid more attention to the association between nutrition and cancer and other chronic diseases in the perspective of inflammation. This paper summarizes the development and application of the diet-related inflammatory index in cancer epidemiological studies based on the literature retrieval of common diet-related inflammatory index. Firstly, we highlight the common diet-related inflammatory indices and their construction methods, such as the Dietary Inflammatory Index, a literature-derived diet-related inflammatory index, and the Empirical Dietary Inflammatory Index, an empirically derived diet-related inflammatory index, and so on. Secondly, the epidemiological research progress on the commonly used diet-related inflammatory indices is briefly introduced. Finally, the advantages and disadvantages of the two types of this inflammatory indices are also briefly described for the purpose of providing reference for nutrition epidemiological studies of cancer and other chronic diseases in China.

Application of lung ultrasound in monitoring bronchopulmonary dysplasia and pulmonary arterial pressure in preterm infants.

OBJECTIVE: The aim of this study was to evaluate the application value of lung ultrasound in monitoring bronchopulmonary dysplasia (BPD) and pulmonary artery pressure in premature infants. PATIENTS AND METHODS: A total of 98 preterm infants diagnosed with BPD in the Fourth Hospital in Shijiazhuang were recruited, and their disease severity was classified as mild (n=32), moderate (n=33), or severe BPD (n=33) based on gestational age and oxygen concentration. Lung ultrasonography of the children was performed. The correlation between lung ventilation scores and disease severity was statistically analyzed, and the discrete optimization results were documented. The pulmonary hypertension indexes of the three groups of children were compared. RESULTS: Aberrant alterations of the pleural line were observed in all included children, and the B-line rose as the disease progressed. The duration of invasive ventilation, medication, and hospital stay increased with disease exacerbation (p<0.05). The three groups significantly differed in terms of ultrasound pulmonary ventilation scores and clinical severity (p<0.05). Only mild BDP was identified by lung ultrasound on the first day of birth (T1), and severe BDP was detectable during the first and second week (T2-T3) as well as the third and fourth week (T4-T5). Severe BPD was associated with significantly higher levels of pulmonary hypertension indices vs. mild and moderate BPD (p<0.05). CONCLUSIONS: Pulmonary ultrasonography demonstrates great potential to predict pulmonary hypertension in children and assesses the disease severity. Pulmonary ultrasound allows for dynamical real-time observation of the pulmonary lesions in children with pulmonary hypertension, thereby revealing the severity of pulmonary hypertension in premature children.

[Related factors of urinary tract infections in inpatients based on real world data].

To analyze the risk factors for urinary tract infection (UTI) among inpatients. The case data of 1 875 inpatients receiving urinary bacterial culture in Beijing Haidian Hospital from October 2019 to May 2021 were analyzed retrospectively. According to the etiological diagnostic criteria of UTI, they were divided into infection group and non-infection group. The species and distribution of pathogens in the infection group were analyzed, and the case data and laboratory indexes were subjected to univariate analysis. The variables with statistical significance were selected for binary logistic regression to analyze the risk factors of urinary tract infection and establish a prediction model. The receiver operating characteristic (ROC) curve was drawn for each parameter included in the model, and the area under the curve (AUC) was calculated. The diagnostic and predictive efficacy of each parameter alone and their combination for UTI were evaluated. So, a total of 1 162 patients with non-infection group and 713 patients with UTI were detected. Among the cultured pathogens, the constituent ratio of Gram-negative bacteria, Gram-positive bacteria and fungi was 57.2%(408/713), 35.9%(256/713) and 6.9%(49/713) respectively. Multivariate analysis showed that, Age, duration of urinary catheterization>7 d, stroke and orthopedic surgery were the risk factors of UTI among inpatients. The use of antibiotics is a protective factor for urinary tract infections. The prediction model of UTI was established by the risk factors, age, duration of urinary catheterization>7 d, stroke, orthopedic surgery, urinary leukocyte esterase, urinary nitrite and Coefficient of variability of red blood cell volume distribution width (RDW-CV). The AUC of the combination of the eight parameters in diagnosing and predicting UTI was 0.835 (95%CI: 0.816-0.855), with the sensitivity of 70.7% and the specificity of 82.8%. In conclusion,the combination of the eight parameters can better assist in the diagnosis and prediction of UTI, and provide an experimental basis for clinicians to judge UTI.

PIWI/piRNA-mediated regulation of signaling pathways in cell apoptosis.

OBJECTIVE: This study aims to summarize the role of PIWIs/piRNAs in cell apoptosis through multiple signaling pathways. The PIWI-interacting RNAs (piRNAs) are among the small non-coding RNAs (sncRNAs) and are mainly expressed in germline cells. PIWI protein is the key to the biogenesis of piRNA. With the deepening of research in recent years, the PIWIs/piRNAs are expressed in a tissue-specific way in somatic cells outside the germline. In addition, researchers have found that the PIWIs/piRNAs play a regulatory role in cell apoptosis, proliferation, and necrosis by regulating key signaling pathways, such as PI3K/Akt signaling pathway, STAT signaling pathway, TGF-ß signaling pathway, and Fas signaling pathway at the transcriptional or post-transcriptional level. However, the PIWIs/piRNAs' role in cell apoptosis and its underlying mechanisms are still not fully understood. This study reviews the regulatory functions of PIWIs/piRNAs in apoptosis from the perspective of the signal pathway. MATERIALS AND METHODS: This study is a narrative review. PubMed and MEDLINE were used as the primary sources to search the following keywords: PIWI/piRNAs, signal pathway, pro-apoptotic, anti-apoptotic, and signaling pathway. RESULTS: PIWIs/piRNAs modulated pro-apoptotic or anti-apoptotic effects in a variety of cells: PIWIs/piRNAs through PI3K/Akt signaling pathway, STAT signaling pathway, TGF-ß signaling pathway, and Fas signaling pathway for pro-apoptotic or anti-apoptotic effects in cells. CONCLUSIONS: Apoptosis is a basic biological phenomenon of cell death, and it also has a great significance and complex molecular biological mechanisms. PIWI/piRNAs are closely related to various types of diseases and play a pro-apoptotic or anti-apoptotic role through the following pathways: PI3K/Akt signaling, STAT signaling, TGF-ß signaling, and Fas signaling pathways.

Association between the Severity of Sarcopenia and Pneumonia in Patients with Stable Schizophrenia: A Prospective Study.

OBJECTIVES: This study investigates the associations between the severity of sarcopenia and pneumonia in patients with stable schizophrenia. MATERIALS AND METHODS: This is a prospective study that includes patients from the rehabilitation wards of two mental health centres in western China, who were diagnosed with stable schizophrenia. Baseline data were collected from these patients between September 1 and September 30, 2020, while patients' data associated with pneumonia, diagnosed and treated by clinicians, were collected between October 2020 and October 2021. The severity of sarcopenia was diagnosed according to the diagnostic criteria defined by the Asian Working Group for Sarcopenia (AWGS) 2019. The association between the severity of sarcopenia and pneumonia in patients with schizophrenia was analyzed with the use of logistic regression analysis. RESULTS: Three hundred and thirty-five patients with stable schizophrenia were enrolled in the prospective study, among whom 242 (72.24%) were≥60 years old, and 229 (68.36%) were males. Among the patients with stable schizophrenia, 130 (38.8%) were diagnosed with non-severe sarcopenia, whereas 47 (14.0%) had severe sarcopenia. Eighty-two (24.5%) of patients with schizophrenia fought pneumonia. Our study showed that the severe sarcopenia group had the highest incidence of pneumonia, followed by the non-severe sarcopenia group (severe sarcopenia vs. non-severe sarcopenia vs. normal, 38.3% vs. 28.46% vs. 17.09%, p=0.005). Compared with the normal group, the non-severe sarcopenia group (OR=1.93, 95%CI: 1.1-3.389) and the severe sarcopenia group (OR=3.011, 95%CI: 1.467-6.183) had a higher risk of pneumonia. We further adjusted the potential confounders such as sex, smoking history, chronic obstructive pulmonary disease (COPD), Patient Health Questionnaire (PHQ-9) score, and benzhexol and confirmed that only the severe sarcopenia group had an increased risk of pneumonia (OR=2.366, 95%CI: 1.078-5.191). CONCLUSIONS: We have demonstrated that severe sarcopenia was associated with pneumonia in patients diagnosed with stable schizophrenia.

[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology].

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

Risk factors associated with catheter-related venous thrombosis: a meta-analysis.

BACKGROUND: So far, the risk factors of catheter-related venous thrombosis (CRVT) are not fully understood. We use evidence-based medicine to find the risk factors of CRVT by pooling the current studies that reported the risk factors of CRVT, aiming to provide guidance for clinical diagnosis and treatment. METHODS: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to July 2021. We included studies that reported the risk factors of CRVT, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. RESULTS: The pooled results show that history of venous thrombosis (odds ratio [OR] = 3.75, 95% confidence interval [CI]: 1.02-13.85; P = 0.047), cancer (OR = 1.74, 95% CI: 1.17-2.57; P = 0.006), infection (OR = 2.13, 95% CI:1.33-3.42; P = 0.002), and multilumina (OR = 3.34, 95% CI:1.48-7.54; P = 0.004) will significantly increase the occurrence of CRVT. However, there is no significant correlation between sex, congenital heart disease, bedridden state, sepsis, mechanical ventilation, anticoagulation therapy, insertion site (left), and CRVT. CONCLUSION: Our research results indicate that history of venous thrombosis, cancer, infection and multilumina are possible risk factors for CRVT, and corresponding preventive measures should be taken clinically.